Biography

Matthew Huber, the David E. Ross Director of the Purdue Institute for a Sustainable Future and professor of earth, atmospheric and planetary sciences, has been chosen to receive the Herbert Newby McCoy Award for outstanding work in the natural sciences.

Huber’s research focuses on global modeling of past, present and future climate conditions as well as climate’s impact on human settlements, managed landscapes, and natural land, ocean and cryosphere ecosystems. His work is helping to explain the physical processes that generate tropical “thermostats” as well as the amplification of warming at the north and south poles, and the environmental, economic, ecological and evolutionary implications of these processes. He is specifically examining the human health and economic impacts under different future greenhouse gas emission scenarios.

“Professor Huber’s scholarship has been internationally recognized for its far-reaching global conclusions on the effect that human activity will have on the Earth’s habitability, resilience and sustainability on long-time horizons,” said Greg Michalski, professor of earth and atmospheric sciences, and analytical chemistry, in nominating Huber for the honor. “His recent achievements in the field of the Earth’s climate — past and future — have had major scientific and societal impacts.”

Huber, who was given the College of Science Research Award in 2022, also received the Atmospheric Sciences Ascent Award from the American Geophysical Union in 2018. The annual Ascent award recognizes excellence in research and leadership in the atmospheric and climate sciences.

Huber says he is honored to have been singled out for the McCoy award.

“I am deeply grateful for this recognition, and thankful to my research team and collaborators who conducted the research, and to my colleagues who supported my nomination,” he said. “But I am most gratified by this award as a concrete recognition by Purdue University that climate change is a real and present danger.”

Huber, who has published over 130 journal papers with more than 14,800 citations, said he is looking forward to the problem-solving stage of his future work. “One can only solve a problem by first defining it properly. Much of my work up to this point has been identifying the unique vulnerabilities of various regions to increasing heat stress — the next phase will be using this knowledge to build out solutions.”

After receiving a doctorate in earth sciences in 2001 from the University of California, Santa Cruz, Huber joined Purdue as an assistant professor in the Department of Earth, Atmospheric, and Planetary Sciences in 2003. He was promoted to associate professor in 2007 and became a full professor in 2011.

Abstract

The history and future of a hot world
The world has warmed many times in the past and it is doing so again. This time the heating is more rapid than at any other time in the past 65 million years and people are responsible. My work has emphasized using information from past warm climates to help us understand how well physics-based climate models capture major climate changes and therefore how much we should believe their future predictions. We now understand that the tropics are very susceptible to global warming and can get hot and humid enough to broadly threaten human ability to work, wellbeing, and health as well as those of other mammals. In my most recent research with collaborators at Penn State University, and with my PhD student Qin Qin Kong, we have demonstrated that the world is much closer to a threshold for human health than previously conjectured. The implication is that hundreds of millions of people, largely in low-to-middle income countries in the tropics and subtropics, will face serious heat-related threats if global warming gets beyond 2°C, and the exposed population increases nearly exponentially with each degree of warming. Major technological and engineering solutions need to be developed and implemented in these regions immediately so that solutions are rolled out in time.

Biography

Yong P. Chen received his BSc and MSc degrees in mathematics from Xi’an Jiaotong University and MIT respectively, and his PhD in Electrical Engineering from Princeton University. After doing a postdoc in physics and nanotechnology at Rice University, he joined the faculty of Purdue University in 2007 and has become the Karl Lark-Horovitz Professor of Physics and Astronomy and Professor of Electrical & Computer Engineering, and Director of Purdue Quantum Science and Engineering Institute. He has also held various international affiliated faculty and research appointments, and is currently on leave to Aarhus University, Denmark as a professor and Villum Investigator. His group works on a wide range of quantum matters and their applications, and has made important contributions to the study of graphene, topological insulators, and cold atoms & molecules. He was a recipient of Masao Horiba Award, NSF CAREER Award, DOD Young Investigator Award and IBM Faculty Award. He is an elected Fellow of American Physical Society (APS) and currently also serves as a commissioner in International Union for Pure and Applied Physics (IUPAP), and a member of the Governance Advisory Board (GAB) of Quantum Science Center, a Department of Energy Quantum Information Science Research Center that was funded in 2020 with $115 million over five years.

Abstract

Making Quantum Matter
Much of our life and future depend on man’s ability to make, control and use new molecules and materials. Recent developments in “quantum science and technology” have brought many unprecedented opportunities and directions in such endeavors. I will describe our research and innovations on synthesis and studies of various quantum matters (materials and molecules) where novel quantum states can profoundly influence observed physical or chemical behaviors. For example, our development of bottom-up-chemically-synthesized graphene has significantly expanded experimental studies and applications of this first “two-dimensional material”, where electrons can behave like relativistic quantum particles, and helped reveal some of the fascinating resulting properties. Our pursuit of better “topological insulators” (another example of quantum materials with relativistic-like electrons) may provide a platform to further realize exotic forms of superconductors and new types of quantum devices. Engineering atomic quantum states and superpositions has enabled us to observe a quantum interference in molecular formation, which may inspire a new approach of “quantum controlled” chemical reaction and intriguing questions connecting quantum materials and chemistry.

Strengthening our theoretical understanding of the quantum world involves both detailed quantitative computations of the relevant equations, and an enhancement of our qualitative intuition. This strategy has enabled the Greene group’s discovery of new phenomena, such as the “trilobite molecule” and the interpretation of puzzling experiments.

Biography

Chris Greene earned his undergraduate BS in physics and mathematics from the University of Nebraska, and his Ph.D. from the University of Chicago. Following a one-year postdoctoral stint at Stanford, he held faculty positions at Louisiana State University and the University of Colorado before joining the Purdue faculty in 2012. He is currently the Albert Overhauser Distinguished Professor of Physics and Astronomy. He has received two prizes from the American Physical Society, namely the inaugural I. I. Rabi Prize and the Davisson-Germer Prize. He has also received the the Hamburg Prize for Theoretical Physics, and was elected to the U.S. National Academy of Sciences in 2019.

Over his career, Greene has mentored 26 postdocs and 26 completed Ph.D. students, two of whom received the annual Thesis Prize awarded by the Division of Atomic, Molecular and Optical Physics of the American Physical Society. With his students, postdocs and other collaborators, he has published more than 350 refereed articles, including more than 50 in the journal Physical Review Letters. His articles have been cited in the literature more than 14,000 times.

Abstract

Making the Counterintuitive Intuitive in the Quantum World
The bizarre nature of quantum mechanical phenomena might seem too counterintuitive, from the perspective of daily life, to ever yield qualitative insights. Yet by diving deep into the quantum world, developing theory to describe experiments that confirm the basic correctness of our quantum mechanical techniques, this research not only demonstrates the confirmation of theory and experiment, but also showcases a deepening of our intuition and our ability to predict new phenomena. Much of the progress in Greene’s research group, both quantitatively and qualitatively, has derived from advancing a theoretical toolkit that identifies a single degree of freedom in the problem to treat adiabatically, i.e., evolving slowly. This lecture will show examples of how use of this simple theoretical idea can address issues across a broad range of scientific problems in condensed matter physics, atomic and molecular physics, and nuclear physics. As one illustration, he will describe his group’s recent theoretical prediction of a way to create a ghost chemical bond.

Research Accomplishments

Greene and his collaborators have developed novel theoretical methods for solving challenging quantum mechanical problems, especially in atomic, molecular and optical physics, but with applications in other physics subfields as well. This research effort has provided the first explanation of some experimental results that were not previously understood, and it has also predicted phenomena such as new types of quantum states that have subsequently been detected in experiments. The following is a selection of some of the major contributions:

• Developed a theoretical formulation to predict the loss rate of atoms from a quantum gas caused by three-body recombination at ultracold temperatures, including the role of the bizarre so-called Efimov states.
• Predicted a novel class of ultra-long-range trilobite molecules that are bound together by a single highly excited Rydberg electron, which by now have been observed by multiple experimental groups.
• Extended adiabatic hyperspherical coordinate theory from atomic and molecular physics to yield insights into systems of interest in condensed matter and in nuclear physics, namely in connection with the fractional quantum Hall effect and the four-neutron problem.
• Established the connection between asymmetrical spectral line shapes in photoabsorption by any system and the phase of oscillation created by an ultrafast laser pulse excitation of the same system.
• Developed a new way to solve the complex quantum mechanical problem of a low energy electron that efficiently destroys a symmetrical polyatomic molecule such as the triatomic hydrogen ion, a process important for the astrochemistry of interstellar clouds.

Biography

Sabre Kais received his master’s and PhD in chemical physics from Hebrew University. After a postdoctoral appointment at Harvard University, he joined Purdue University’s Department of Chemistry in 1994 as an assistant professor. He became full professor of chemical physics in 2002.

Kais has made numerous important contributions to quantum theory and quantum computing. His current research includes quantum machine learning,

quantum algorithms, quantum entanglement, and adiabatic quantum computing.He has authored and co-authored four book chapters, more than 230 peer-reviewed articles, and made 155 conference presentations, including many invited lectures. He also has served on the editorial boards of several chemistry and physics journals.

Kais is former director of the National Science Foundation’s Center for Chemical Innovation, Quantum Information for Quantum Chemistry, and has been the recipient of the National Science Foundation Career Award, the Purdue University Faculty Scholar Award, and the Guggenheim Fellowship Award. In 2007, Kais became an elected fellow of the American Physical Society and an elected fellow of the American Association for the Advancement of Science. In 2012, he received the Sigma Xi Research Award. He has courtesy professorship appointments in the Department of Computer Science and the Department of Physics at Purdue.

Abstract

Quantum Information and Computation for Complex Chemical Systems
New research is focusing on understanding chemistry from the viewpoint of quantum information — developing techniques and quantum computing algorithms for solving important problems in chemistry.

In his talk, Kais will give a brief overview of the recent advances in both hardware and software research in quantum computing. He will present the challenging problems in quantum computing for complex chemical systems, focusing on electronic structure and open quantum dynamics calculations. Kais also will discuss three related approaches to quantum chemistry calculations: the quantum circuit model, the adiabatic quantum computing model, and the quantum machine learning approach.

Research Accomplishments

Sabre Kais has made numerous highly creative and important contributions to quantum theory and quantum computing. These include the creation of novel quantum computing algorithms for chemical calculations and the formulation of finite size scaling algorithms for assessing the stability of atomic and molecular systems.

The following is a summary of Kais’ most significant and recent contributions to the field of quantum information and quantum computation for chemistry:

• Quantum Machine Learning — Developed a hybrid quantum algorithm employing a restricted Boltzmann machine to obtain accurate molecular potential energy surfaces for simple molecular systems.
• Quantum Algorithms — Made significant progress on elucidating, optimizing, and implementing ground state energy algorithms — in particular, electronic structure algorithms on quantum computers. He also has developed quantum algorithms for solving Poisson’s equation.
• Quantum Entanglement — Established that entanglement can be used as an alternative measure of the electron correlation in quantum chemistry calculations. He clarified the role of entanglement in quantum phase transitions, avian compass, photosynthesis, quantum computing with polar molecules and chemical reactions.
• Quantum Coherence — Developed a new quantum formalism to understand the role of quantum coherence in complex systems and used this strategy to prove that the efficiency of photocell can be greatly enhanced by quantum coherence. These results suggest a promising novel design of photosynthesis-mimicking photovoltaic devices.
• Adiabatic Quantum Computing — Made recent breakthroughs in the field of adiabatic quantum computing by developing an exact mapping between the electronic structure Hamiltonian and the Ising Hamiltonian which allow for the quantum D-Wave machine to simulate hundreds of connected spins (qubits) interacting with an Ising-type Hamiltonian.

Distinguished Lecture Video

Biography

Natalia Dudareva is a Distinguished Professor and teaches in the departments of Biochemistry and Horticulture and Landscape Architecture at Purdue. She earned her bachelor’s and master’s degrees in biochemistry from Novosibirsk State University in Russia. She received a PhD in biochemistry and molecular biology from the O.V. Palladin Institute of Biochemistry, Kiev, Ukraine, and a second PhD in plant molecular biology from the Louis Pasteur University, Strasbourg, France.

Dudareva came to Purdue in 1997 and was named a distinguished professor in 2010. She joined the Department of Biochemistry in 2013.

Dudareva has published 116 papers, 25 book chapters and two books, and has given 200 invited lectures at conferences and other universities. She has received recognition for her research as a Purdue University Faculty Scholar and the Wickersham Chair of Excellence in Agricultural Research. She has been awarded the Purdue University Agricultural Research Award, the Sigma Xi Faculty Research Award, and the Alexander von Humboldt Research Award (Germany). She is a fellow of the American Association for the Advancement of Science.

Abstract

Look Who’s Talking: Chemical Language of Plants
Plants have exploited the language of small chemicals for interacting with their environment more extensively than any other living organism. A diversity of volatile molecules released by plants plays essential roles in their growth, development, reproduction, defense and communication. They also influence atmospheric chemistry and climate, and humans use them as flavors, fragrances, biofuels, insecticides and pharmaceuticals.

Dudareva will discuss different aspects of volatile emission: from volatiles’ function and their perception by insects, to biosynthesis, regulation and how plants deploy these compounds into the atmosphere. In addition, she will talk about what limits volatile trait modification and will outline biotechnological approaches for improving crop productivity and defense, as well as improving flavor and aroma.

Research Accomplishments

Over the past 20 years, Dudareva has explored the molecular mechanisms of plant metabolism and how plants produce volatile compounds, scent and taste components that are essential for successful pollination, fruit development and plant defense.

Using biochemical, genetic and molecular approaches, Dudareva has provided insights into fundamental plant biology. She also has pioneered research into the biosynthetic pathways that underpin plants’ strategies for attracting pollinators; communicating with other plants; and defending themselves from pathogens, parasites and herbivores.

Dudareva’s research has led to the discovery of a microbial-like pathway in plants to produce phenylalanine, an amino acid that is a vital component of proteins. She also showed that active biological mechanisms are involved in transporting plant volatiles from plant cells to the atmosphere, a finding that could overturn the prevailing model of volatile emission as a process that occurs solely by diffusion.

Other research by Dudareva and her collaborators includes:

• Elucidating the molecular architecture and dynamics of phenylalanine biosynthesis in plants.
• Deciphering the complex terpenoid metabolic network and its regulation.
• Discovering the biochemical pathways leading to benzoic acid formation.
• Identifying biomolecular processes involved in the release of plant volatiles into the atmosphere.

Biography

Alice Watson Kramer Distinguished Professor of Chemistry and professor of biomedical engineering

Jean Chmielewski earned her Bachelor of Chemistry degree from St. Joseph’s University in Philadelphia and earned her PhD in organic chemistry from Columbia University. After postdoctoral fellowships at Rockefeller University and the University of California, Berkeley, she joined Purdue as an assistant professor in 1990 and received a distinguished professorship in 2005.

Her research interests are in chemical biology and bioorganic chemistry, including work in the design of agents to modulate protein-protein interactions, the development of agents that target intracellular pathogenic bacteria, novel agents to eradicate HIV reservoirs and peptide-based biomaterials for regenerative medicine.

Chmielewski has received recognition for her research and teaching, including a National Institutes of Health First Award, a National Science Foundation National Young Investigator Award, an Alfred P. Sloan Award, an Arthur C. Cope Scholar Award and an Edward Leete Award from the American Chemical Society. She also has received several teaching awards, including the Charles B. Murphy Award — Purdue’s highest teaching award. She is a fellow of the American Association for the Advancement of Science.

Abstract

Designing Unique Chemical Approaches to Solve Significant Issues in Human Health
Molecular strategies will be presented to target and kill pathogenic bacteria residing within human cells and to promote the penetration of antiviral agents across the blood-brain barrier with the goal of eradicating HIV reservoirs. Her talk will focus on designing chemical approaches and therapeutics to solve significant issues in human health and disease. Her presentation will provide insights into two different areas of chemical biology:

• The development of agents that target intracellular pathogenic bacteria.
• The design of molecules to promote the penetration of anti-HIV agents across the blood-brain barrier.

Research Accomplishments

Professor Chmielewski has forged an interdisciplinary research program to address fundamentally important problems at the intersection of chemistry, biology and medicine. She focuses her research on four interrelated areas:

• Modulating protein assembly.
• Inhibiting drug resistance efflux transporters.
• Targeting intracellular pathogenic bacteria.
• Bionanotechnology.

In the early 1990s, Chmielewski was one of the first researchers to develop agents that modulate protein-protein interactions, revealing their potential to serve as therapeutic targets. Her publications, using cross-linked peptide fragments that mimic protein interfaces, were among the first in this field of drug discovery. Her research also led to potent protein-protein interaction inhibitors of anti-HIV targets, transcription factors and pore-forming proteins of pathogenic bacteria.

Over the past decade, Chmielewski has begun a program that blocks multidrug resistance transporters, which are major proteins limiting the anatomical and cellular accumulation of therapeutics for diseases such as cancer, HIV and malaria. Her research provides an innovative strategy to block both the efflux function of transporters and deliver the required therapy to the disease site. This unique project tackles a wide range of diseases with a single interdisciplinary platform technology, and it includes new strategies to limit the formation of HIV reservoirs in the brain and anti-malaria therapies that directly target resistance mechanisms.

Designing shuttles to bring therapeutic agents into cells has been another hallmark of Chmielewski’s research over the past two decades. For example, she recently developed a novel class of biomimetic peptides, cationic amphiphilic polyproline helices, that efficiently enter cells and eradicate pathogenic bacteria at their specific subcellular site. This has provided agents that target and kill bacteria — including mycobacterium tuberculosis, salmonella and listeria — within human macrophages. These agents also are being pursued as novel preclinical drug candidates for treatment of complicated skin infections and hospital-acquired pneumonia.

Chmielewski has designed a hierarchical assembly of modified triple helical collagen and coiled-coil mimetic peptides for use in regenerative medicine. For example, collagen peptides with strategically placed metal binding sites have led to an array of higher-order structures, with unique cell-binding capabilities and controlled protein release. These biocompatible materials have potential for use in tissue engineering and regenerative medicine, which she has demonstrated with recent work in her laboratories on stem cell differentiation and scaffold-mediated cell assembly. These assemblies also have been used to bind histidine-tagged cargoes in drug delivery.

Biography

Jian Kang Zhu is a Distinguished Professor of Plant Biology, Departments of Horticulture and Landscape Architecture and Biochemistry at Purdue University, and Director of the Shanghai Center for Plant Stress Biology, Chinese Academy of Sciences. He earned his bachelor’s degree in soils and agricultural chemistry from Beijing Agricultural University; his master’s degree in botany from the University of California, Riverside, and his doctorate in plant physiology from Purdue. Previously he was at the University of California, Riverside, where he was the Jane Johnson Chair Professor in the Department of Botany and Plant Sciences. Prior to UC Riverside, he spent eight years as a faculty member at the University of Arizona, Tucson. His research has sought to elucidate the signaling pathways in plants that govern their responses to environmental stresses such as drought, soil salinity and freezing temperatures. He is also interested in epigenetics, particularly how the DNA methylation mark is deposited and removed.

Abstract

Decoding the epigenetic language of life
Epigenetics refers to the study of heritable information that is not contained in DNA sequence. An important epigenetic mark conserved in mammals and plants is DNA methylation, a chemical modification of DNA that controls gene function. Proper DNA methylation patterns are critical for development, diseases and stress responses in humans as well as in plants. Plants are excellent biological systems to study how DNA methylation patterns are generated. DNA methyltransferase enzymes that deposit the DNA methylation mark are guided to specific DNA sequences, and DNA demethylase enzymes that remove the DNA methylation mark are also guided to distinctive sequences to erase unwanted DNA methylation. I will describe work in my lab that has shed light on how DNA methyltransferases and demethylases are guided to specific sequences, and how the antagonistic actions of the enzymes are coordinated to generate proper DNA methylation patterns. I will also describe some of our recent work on how DNA methylation influences transgenerational inheritance.

Research Accomplishments

• Elucidated the biochemical pathway for the erasure of DNA methylation marks
• Discovered a protein complex that targets DNA demethylases to specific genomic regions
•  Proposed the concept of a methylstat that senses and regulates genomic DNA methylation levels
• Demonstrated a role for the RNA-directed DNA methylation pathway in gene allele interactions in hybrid plants
• Identified small chemical molecules with very potent activities in protecting plants from drought stress

Detailed description of research

DNA methylation is a conserved epigenetic mark important for organismal development, diseases and stress responses in plants and mammals. In 2002, Jian-Kang Zhu’s group discovered the first DNA demethylase enzyme, ROS1. This is the long sought after enzyme that functions to erase unwanted DNA methylation marks and prevent DNA methylation-mediated gene silencing. In the last several years, his lab has identified most of the enzymes that function downstream of ROS1 in the base excision repair pathway of active DNA demethylation, including the 3’ DNA phosphatase ZDP, AP endonuclease APE1L and DNA ligase 1.  His group designed an innovative genetic screen that resulted in the discovery of an anti-silencing protein complex composed of several regulators of ROS1 function. These regulators include the novel histone acetyltransferase IDM1, alpha-crystallin domain proteins IDM2 and IDM3, the methyl-DNA binding protein MBD7, and two transposon-derived proteins, HDP1 and HDP2. This complex recognizes highly methylated genomic regions and creates histone acetylation marks that allow ROS1 to be recruited to demethylate the genomic DNA. The discovery of this protein complex that regulates demethylase function contributes significantly to our understanding of the targeting of DNA demethylase for precise control of DNA methylation reprogramming during development, stress responses and diseases. Recently, his group elucidated the mechanism of coordination between DNA methylation and demethylation activities, and proposed the concept of a methylstat that senses the DNA methylation and demethylation activities and regulates genomic DNA methylation levels by fine-tuning demethylase gene expression. They found that DNA methylation greatly influences the interaction between some gene alleles in hybrids. In addition, they found a new chemical inhibitor of epigenetic silencing, and identified several new players in the RNA-directed DNA methylation pathway.

In abiotic stress research, his group continues to focus on the signal transduction pathway for abscisic acid (ABA), the most important plant hormone for resistance to drought and other abiotic stresses. His lab contributed to the discovery of ABA receptors and to the elucidation of the structure of the receptor complex, and for the first time achieved the in vitro reconstitution of the core ABA signaling pathway in a test tube. Since joining Purdue, his lab has discovered a unique pathway that plants use to control lateral root growth under stress conditions. They found that one of the ABA receptors, PYL8, interacts directly with a Myb transcription factor in the nucleus and enhances its transcriptional activity to promote lateral root growth, rather than interacting with protein phosphatases in the known core ABA signaling pathway. In collaboration with Prof. Andy Tao’s lab, his group identified several dozens of new proteins that are phosphorylated by ABA-activated SnRK2 protein kinases. These phosphoproteins are important effectors of ABA action in plant cells. Therefore, their identification provided significant new insights into the cellular action of ABA. Recently, his group found that the second messenger nitric oxide (NO) that is induced by ABA, causes S-nitrosylation and inhibition of the SnRK2 kinases. The study revealed how NO functions to desensitize ABA signaling in plants. In addition, his group discovered ABA-mimicking small chemicals that can be applied to plants to activate the ABA pathway to close stomata to reduce transpirational water loss and to induce the expression of drought responsive genes, leading to drought resistance. These chemicals are easy to synthesize, non-toxic, much less expansive and more stable than ABA, and thus have enormous potential for applications in agriculture, turfgrass and horticultural industries to protect plants from drought stress and benefit the environment by reducing the consumption of precious freshwater resources.

Biography

Arun K. Ghosh is the Ian P. Rothwell Distinguished Professor of Chemistry, Medicinal Chemistry and Molecular Pharmacology at Purdue University. He received his BS and MS degrees in chemistry at the University of Calcutta (1979) and the Indian Institute of Technology (1981), Kanpur, respectively. He obtained his PhD (1985) from the University of Pittsburgh. He then pursued postdoctoral research at Harvard University (1985-1988). Professor Ghosh’s research interests include diverse areas of organic, bioorganic and medicinal chemistry with particular emphasis on organic synthesis and protein-structure-based design of biomolecules.

Professor Ghosh has been awarded the Chemical Research Society of India Medal (2012), NIH Merit Award (2011), IUPAC-Richter Prize in Medicinal Chemistry (2010), American Chemical Society’s Arthur C. Cope Senior Scholar Award (2010), ACS Robert Scarborough Excellence in Medicinal Chemistry Award (2008), and Novartis Chemistry Lectureship (2010-2011). He is a Fellow of the Royal Chemical Society, FRSC (2015) and a Fellow of American Association for the Advancement of Science, AAAS (2005).

He was a University Scholar, University of Illinois (1998-2001) and National Scholar, Government of India (1976-1981). He has been on the editorial advisory boards of numerous organic and medicinal chemistry international journals.

Ghosh has published over 285 scientific research papers. He is an inventor of over 50 U.S. patents and patent applications on inhibitors of HIV-1 protease, β-secretase, SARS and anti-cancer agents. He has published two books entitled, “Structure-based Design of Drugs and Other Bioactive Molecules—Tools and Strategies” (Wiley-VCH, 2014) and “Aspartic Acid Proteases as Therapeutic Targets” (Wiley-VCH, 2010).

Abstract

Historically, nature has provided an incredible variety of structurally complex and biologically important molecules. Many of today’s medicines are obtained directly from these natural products or from their derivatives.

Our chemical syntheses of medicinally important natural products and exploration of their function brought a unique perspective to our team’s drug design using the protein X-ray structure as a guide. We sought to develop innovative molecular probes against proteins implicated in the pathogenesis of human diseases.

The treatment of patients with HIV/AIDS continues to be very challenging due to viral mutation and rapid emergence of drug resistance. Our research efforts promoting “backbone binding” led to the HIV protease inhibitor-based drug, darunavir, for the treatment for all HIV/AIDS patients, including patients harboring drug-resistant HIV.

Also, we have led the important groundwork for structure-based design of inhibitors of memapsin 2 (β-secretase), an exciting drugdesign target for the treatment of Alzheimer’s disease. A number of potent and selective inhibitors from our laboratories show potential for clinical development. This presentation will feature novel design concepts, general strategies and development tools for HIV-1 protease inhibitors against HIV/AIDS and β-secretase inhibitors against Alzheimer’s disease.

Research Accomplishments

Professor Ghosh is one of the world’s leading authorities in protein X-ray structurebased molecular design. He has been designing innovative molecular scaffolds and templates by drawing inspiration from nature.

Ghosh developed the “backbone binding” concept for designing HIV protease inhibitors to combat drug resistance. He conceptualized that a molecule that maximizes interactions, particularly hydrogen bonding interactions with backbone atoms would likely conserve these interactions with mutant proteases, since the active site backbone conformation of mutant proteases is minimally distorted.

His laboratory has created a range of novel inhibitors that grasp the enzyme’s backbone like a “molecular crab.” Darunavir was designed to maintain antiviral activity against a wide spectrum of drug-resistant HIV-1 variants. Darunavir received FDA approval in 2006 as the first treatment for patients harboring multidrug-resistant HIV. In 2008, it was approved as first-line therapy for all HIV/AIDS patients including pediatrics. Darunavir’s ability to delay the onset of drug-resistance has set new standards for HIV/AIDS treatment.

Ghosh also has pioneered the design and synthesis of inhibitors of β-secretase or memapsin 2 (BACE), a key enzyme responsible for plaque production in the brain leading to Alzheimer’s disease (AD). Ghosh designed the first substrate-based β-secretase inhibitor, determined the first X-ray crystal structure of his inhibitor complexed with β-secretase, and established the X-ray structure-based evolution of nonpeptide inhibitors. His laboratory designed inhibitors with remarkable selectivity over other physiologically important enzymes.

Many inhibitors have been shown to penetrate the blood-brain barrier, inhibit plaque production in the brain of AD mice and rescue their cognitive decline. The work from Ghosh’s laboratories set the groundwork for tools and strategies for BACE inhibitors. A number of BACE inhibitors from other laboratories are now in advanced clinical development, showing potential for a disease-modifying treatment for Alzheimer’s disease.

Ghosh developed a range of cysteine protease inhibitors against SARS-CoV & MERS-CoV coronavirus proteases. He directed the design and development of a number of potent nonpeptide inhibitors for SARS-CoV 3CLpro (3C-like protease) and SARS-CoV PLpro (papain-like protease). This work on PLpro provided a first proof-of-principle that it is a viable target for development of antivirals directed against the SARS & MERS virus.

Ghosh’s synthesis and exploration of biology of natural products is extensive, including more than three-dozen structurally diverse families. Laulimalide and pelorusides are sponge-derived macrolides isolated in only miniscule quantities. Following laboratory syntheses of these natural products, Ghosh’s collaborative studies discovered that these drugs stabilize microtubules by binding at a previously unknown drug-binding site. In addition, laulimalide and peloruside were able to enhance tubulin  ssembly synergistically with paclitaxel.

Ghosh also synthesized lasonolide, leading to elucidation of its mechanism of action for anti-tumor activity. He also synthesized potent spliceosome inhibitors, herboxidienes, pladienolide and  pliceostatins, and established critical structure-activity studies. This has set the stage for the design of less complex spliceosome inhibitor-based anti-cancer drug development.

In the context of chemical syntheses, Ghosh has developed new and practical chemistry for asymmetric carbon-carbon and carbon-heteroatom bond forming reactions. These methods have been extensively employed in the synthesis of bioactive targets.

Biography

Distinguished Professor of Earth, Atmospheric and Planetary Sciences, Physics and Astronomy, and Aeronautical and Astronautical Engineering at Purdue University

Jay Melosh received an AB degree in physics (magna cum laude) from Princeton University in 1969 and a PhD in physics and geology from Caltech in 1973. 

His principal research interests are impact cratering, planetary tectonics, and the physics of earthquakes and landslides. His recent research includes studies of the giant impact origin of the moon, the K/T impact that extinguished the dinosaurs, the ejection of rocks from their parent bodies and the origin and transfer of life between the planets

He is a science team member of NASA’s Deep Impact mission that successfully cratered comet Tempel 1 on July 4, 2005, and flew by comet Hartley 2 on Nov. 9, 2010. He also is a co-investigator of the GRAIL mission that returned detailed data on the Moon’s gravity field.

Professor Melosh is a Fellow of the Meteoritical Society, the Geological Society of America, the American Geophysical Union and the American Association for the Advancement of Science. He was awarded the Barringer Medal of the Meteoritical Society in 1999, the Gilbert prize of the Geological Society of America in 2001 and the Hess Medal of the American Geophysical Union in 2008.

He was a Guggenheim Fellow in 1996-97 and a Humboldt Fellow at the Bavarian Geological Institute in Bayreuth, Germany, in 2005-06. Asteroid #8216 was named “Melosh” in his honor. He was elected to the U.S. National Academy of Sciences in 2003 and the American Academy of Arts and Sciences in 2011.

He has published approximately 180 technical papers, edited two books and is the author of the text “Planetary Surface Processes” with Cambridge University Press.

Abstract

Collisions with asteroids and comets used to be the stuff of science fiction. Starting with the Apollo missions’ revelations about our Moon, however, it has gradually dawned on the scientific world that collisions between objects from microscopic to planetary dominated nearly every aspect of our planetary system’s birth. Long after the birth of our planet, a rare asteroid impact initiated the extinction of the dinosaurs. As recently as Feb. 15, 2013, the atmospheric disintegration of a building-sized space rock terrified residents of the city of Chelyabinsk, Siberia. Few people in Greater Lafayette are aware that the scar from an ancient asteroid impact lies only 30 miles away, underneath the town of Kentland, Indiana. Impacts on Mars have sent us samples of that planet in the form of meteorites and just might have once transferred living organisms between our two planets. Modern computer models are now revealing just what happens when an irresistible force — a speeding asteroid — meets an immovable object such as the Earth, Mars or the Moon.

Research Accomplishments

Professor Melosh is the world authority on the subject of meteorite impact cratering. Aside from many individual papers, he published a monograph titled “Impact Cratering: A Geologic Process” in 1989 that is still recognized as the definitive exposition of the subject. Almost every modern scientific paper on impact cratering cites his book.

His advice on impact craters is widely sought by industry, government agencies and TV documentary producers (for his appearance in many documentaries on impacts, asteroids and extinctions, he is cited in the movie star database IMDb). 

Melosh’s work on impact craters began in 1975 with a fundamental analysis of the stability of freshly formed craters that showed that the rock around an impact crater is unusually weak. He explained this weakening by a novel mechanism he named “acoustic fluidization” that also explains the atypical mechanical behavior of very large landslides and earthquakes.

His mechanism for explaining the anomalous weakness of earthquake faults is one of the important contenders for the resolution of the still-unsolved problem of what causes the extreme weakness of mature faults like the San Andreas. 

In the 1980s, he played a leading role in understanding the mechanism by which the Martian and Lunar meteorites are blasted off their parent planets. His “spallation mechanism” is currently accepted as the means by which this ejection occurs. He extended this spallation idea to propose that living organisms may survive exchange between planets, an idea that he has continued to explore in many publications and experiments with biologist colleague Wayne Nicholson.

This idea of “lithopanspermia” is now widely accepted as a paradigm among astrobiologists. One of his most highly cited papers concerns the ability of ordinary soil bacteria to survive in the space environment. 

Melosh played a key role in establishing the giant impact origin of the Moon and in deducing the consequences of that impact for the early Earth and the formation of its core. More recently, he collaborated with David Rubie of the BGI in Germany to perform a definitive analysis of the equilibration of core metal and magma on the early Earth that, for the first time, explains the strange siderophile element abundances in the Earth’s mantle.

In the wake of Luis and Walter Alvarez’s proposal that the K/T extinction was caused by a large impact, Melosh and colleagues suggested that the global rainback of fast distal ejecta was the immediate cause of land extinctions, which were caused by thermal radiation from the infalling ejecta. These predictions were largely validated by the 1994 impact of comet Shoemaker/Levy 9 on Jupiter.

He also made the first accurate estimate of the size of S/L-9 from a tidal breakup model and demonstrated that previously enigmatic crater chains on Callisto, a moon of Jupiter, were the result of impacts by tidally dispersed comets. He has continued to contribute fundamental ideas to the study of both large and small impact craters.

Biography

Andrew Weiner is the Scifres Family Distinguished Professor of Electrical and Computer Engineering. In 2008 he was elected to membership in the National Academy of Engineering, and in 2009 he was named a Department of Defense National Security Science and Engineering Faculty Fellow.

Weiner recently served a three-year term as Chair of the National Academy’s U.S. Frontiers of Engineering meeting. At present, he serves as editor-in-chief of Optics Express, an all-electronic, open-access journal publishing more than 3,000 papers a year emphasizing innovations in all aspects of optics and photonics.

After Weiner earned his ScD in electrical engineering in 1984 from the Massachusetts Institute of Technology, he joined Bellcore, at that time a premier telecommunications industry research organization, first as a member of technical staff and later as manager of Ultrafast Optics and Optical Signal Processing Research. He joined Purdue as a professor in 1992 and has since graduated 30 PhD students.

Professor Weiner’s research focuses on ultrafast optics, with an emphasis on processing of extremely high-speed lightwave signals. He is known for his advancements in the programmable generation of arbitrary ultrashort pulse waveforms, which has found application both in fiber optic networks and in ultrafast optical science laboratories around the world.

He is the author of a textbook entitled Ultrafast Optics, has published eight book chapters and more than 270 journal articles. Weiner holds 15 U.S. patents. His numerous awards include the Hertz Foundation Doctoral Thesis Prize (1984), the Optical Society of America’s Adolph Lomb Medal (1990) and R.W. Wood Prize (2008), the International Commission on Optics Prize (1997), and the IEEE Photonics Society’s William Streifer Scientific Achievement Award (1999) and Quantum Electronics Prize (2011).

At Purdue, he has been recognized with the inaugural Research Excellence Award from the Schools of Engineering (2003) and with the Provost’s Outstanding Graduate Student Mentor Award (2008).

Abstract

Lasers capable of generating picosecond and femtosecond pulses of light are now firmly established and are widely deployed. Professor Weiner’s pioneering work on programmable shaping of ultrafast laser fields into arbitrary waveforms has resulted in substantial impact, both enabling new ultrafast science and influencing practical applications in transmission of high-speed lightwave and wireless signals. The lecture begins with a brief introduction to ultrafast optics and then specifically addresses methods permitting shaping of ultrafast laser fields on time scales too fast for direct electronic control. Several examples illustrating a new area of science — in which researchers worldwide use shaped laser pulses as tools to manipulate nanoscopic and quantum mechanical processes, including simple photochemical reactions — will be described. The final section of the lecture focuses on recent work from the Weiner Laboratory in which pulse shaping and related photonic processing tools are applied to enhance transmission both of lightwave signals over fiber optic cables and of wireless signals in highly scattering indoor propagation environments.

Research Accomplishments

Professor Andrew Weiner is widely known for his seminal contributions to the science of ultrashort optical pulse generation with arbitrary waveforms and for the applications of this science in a number of different technologies.

The impact of his work has been significant. Pulse shaping is now employed in ultrafast optics laboratories around the world, enabling research in fields as diverse as coherent quantum control, single cycle optical pulse generation, nonlinear optical microscopy and imaging, high-speed lightwave communications, and ultrabroadband radio-frequency photonics.

Weiner’s contributions include the first demonstration of femtosecond time scale pulse shaping (1988, joint with J.P. Heritage) and invention of the first programmable pulse shaping methods (1990-92). The development of programmable pulse shaping technology, using liquid crystal spatial light modulators patented and first demonstrated by Weiner, was a key step that enabled the widespread adoption of this technique. Weiner’s pioneering work spurred others to explore new applications and to develop new types of spatial light modulators suitable for use in pulse shaping systems.

The ability to program pulse shapes enabled new classes of adaptive pulse shaping systems, in which waveforms selected for optimum experimental results are obtained automatically via iterative computer learning algorithms. The basic optical layout demonstrated and popularized by Weiner has been adapted to realize commercial products, ranging from high-intensity femtosecond amplifiers used for a broad spectrum of research in ultrafast optical science to modules used in the optical communications industry.

Weiner also is known for a series of elegant, groundbreaking experiments demonstrating the potential of optical pulse shaping to open up areas in science and new applications in technology. His 1990 Science paper on application of femtosecond pulse sequences for selective amplification of optical phonons in molecular crystals is one of the earliest examples of the now very active field of coherent and quantum control, in which specially controlled ultrafast laser waveforms are used to manipulate light-matter interactions. Examples of experiments in this field include selective enhancement of high harmonic radiation from atoms driven by strong laser fields, laser controlled chemistry, spatially selective excitation of plasmons in metallic nanostructures and spectrally (hence chemically) selective microscopy.

Weiner conceived a spectral phase equalizer principle for programmable compensation of pulse spreading and distortion due to frequency-dependent delay phenomena, which is now frequently used for applications ranging from short pulse transmission in optical fibers to compression of pulses in high power amplifier systems, at the foci of microscopes and to durations approaching the single cycle limit. Femtosecond pulse shaping is a key enabler for all of this work.

In recent years, Professor Weiner has continued to exploit ideas and technologies originating from the fields of ultrafast optics and pulse shaping to develop new concepts for manipulation and processing of ultrahigh-speed signals. Through this work, he has opened up three exciting new lines of research, as summarized briefly below.

Line-by-Line Pulse Shaping

The new field of femtosecond frequency combs, recognized with the 2005 Nobel Prize in Physics for its revolutionary impact on optical frequency metrology, fundamentally deals with optical spectra at the individual spectral line level. Through his work for the first time applying pulse shaping to the individual lines of a frequency comb, new opportunities now exist in areas ranging from high-resolution nonlinear spectroscopy to secure communications.

Ultrabroadband Radio-Frequency Photonics

Radio-frequency (RF) systems are ubiquitous in applications ranging from radar to wireless communications. Conventional RF systems are designed from a frequency domain perspective, with signals operating at low instantaneous bandwidth and well-defined center frequency. Femtosecond optics, on the other hand, is fundamentally time-domain in nature, and complex waveform control (thanks, for example, to pulse shaping) is now common. The Weiner group has performed groundbreaking experiments demonstrating that ultrafast photonics approaches, including pulse shaping, can be exploited for generating and processing user-defined ultrabroadband RF electrical signals with tens of GHz instantaneous bandwidths (in some cases approaching 1 THz), far outstripping purely electronic approaches and opening completely new possibilities.

Novel Signal Processing with Micro-Resonators

Weiner, working with Professor M. Qi, conceived and demonstrated pulse shaping chips to achieve arbitrary RF waveform generation and demonstrated a new scheme, based on asymmetrically coupled nonlinear resonators, for one-way transmission of light, resulting in optical diode action with nearly three order of magnitude contrast between forward and reverse propagation. Further work on nonlinear micro-resonator chips produced sub-picosecond pulses at rates as high as hundreds of GHz, as well as first delineation of coherent (low noise), and partially coherent (noisy) modes of operation. Control of coherence and noise of micro-resonator-generated combs has since emerged as a major topic in this rapidly growing field.

Biography

Distinguished Professor and Head of the Department of Nutrition Science

In 2011, Dr. Weaver was appointed to the Institute of Medicine’s Food and Nutrition Board. The previous year she was elected to membership in the Institute of Medicine of the National Academies, of which she is a member of the Food and Nutrition Board. In 2008, she became deputy director of the National Institutes of Health-funded Indiana Clinical and Translational Science Institute. From 2000 to 2010, she was director of the NIH Purdue-UAB Botanical Research Center to study dietary supplements containing polyphenolics for age-related diseases.

Dr. Weaver is past president of the American Society for Nutrition. She is on the Board of Trustees of the International Life Sciences Institute and National Osteoporosis Foundation. She has published more than 260 research articles, and has trained 37 doctorate and 18 master’s degree students.

Her honors include the Purdue outstanding teaching award (1985), Health Promotion Award for Women (1993) and the Sigma Xi Faculty Research Award (2006); the Institute of Food Technologists Babcock Hart Award (1997); the USDA A.O. Atwater Lecture Award (2003), the American Society for Nutrition Robert H. Herman Award (2009), the Natural Products Association’s Burton Kallman Scientific Award (2010), and the Linus Pauling Research Prize (2011). Dr. Weaver was appointed to the 2005 Dietary Guidelines Advisory Committee for Americans.

Abstract

Calcium is one of four shortfall nutrients targeted by the Dietary Guidelines for Americans Advisory Committee that needs attention. The Weaver laboratory at Purdue quantified calcium intakes for optimizing bone accretion during puberty, a primary strategy to prevent osteoporosis later in life. These intakes have formed the basis for the recommended calcium intakes for North America, the Dietary Guidelines for Americans food patterns for dairy intake, and the Surgeon General’s Report for Bone Health for adolescents. Professor Weaver’s team uses controlled feeding studies and calcium tracers to determine the role of diet, sex, race, hormones and body size in building peak bone mass during adolescence. Her unique approach to addressing these questions has been the use of summer research camps called Camp Calcium to provide a controlled environment. Eleven camps have been conducted over 20 years. Another use of calcium tracers has been to screen interventions for reducing bone loss following menopause.

Research Accomplishments

During my doctoral work, I studied accumulation of nuclear fission products by plants and methods of their removal by processing in an era of public safety concern over nuclear power plants. I learned isotopic tracer techniques and continued my studies of nutrition, food science, chemistry and plant physiology. When I arrived at Purdue in 1978, it was a natural transition to apply these techniques to the study of essential minerals.

With the 1980s came an awareness of the growing prevalence of osteoporosis and a possible role of diet and other lifestyle choices. However, there were scant quantitative data upon which to make dietary recommendations. Calcium was an obvious nutrient to study because it is the dominant mineral in bone and dietary intake is low.

We began using intrinsic labeling techniques to determine calcium absorption from common dietary sources including dairy products, plants and supplements, and worked with manufacturers to evaluate the potential for fortified foods. More recently, we have been studying dietary constituents that can enhance calcium absorption and the role of gut microbiota.

As half of adult bone mass is accumulated during adolescence, we designed Camp Calcium, a metabolic study environment run as a summer camp, to determine factors that influence bone accretion.

We determined optimal calcium intakes and learned that diet is as important as race, that boys are more efficient in using calcium than girls, that Asian girls are more efficient than blacks who are more efficient than whites, that increased body mass index increases calcium retention when calcium intakes are maximum, and that IGF-1 is the most important regulator of calcium utilization. Dietary calcium increases bone balance primarily through decreasing bone resorption.

As much bone can be lost following menopause as was gained in adolescence. The traditional approach to evaluating effective interventions requires years and a large number of volunteers. We developed a novel rapid screening method requiring few participants and short interventions.

Most of our work is done with multidisciplinary teams. This facilitates addressing complex questions and is more fun. This realization has led me to be involved in many multidisciplinary research ventures including the NIH Botanicals Research Center for Age Related Diseases, the Indiana Clinical and Translational Sciences Center, and the new Women’s Global Health Initiative.

Biography

Distinguished Professor in the Department of Biochemistry

Clint Chapple has long been fascinated by the compounds that plants produce and the diverse catalytic repertoire that is required to make them. Armed with training in the fundamentals of plant form and function that he gained through his B.Sc. and M.Sc. in botany at the University of Guelph, he continued at the same institution to earn a Ph.D. in chemistry with Dr. Brian Ellis studying the biosynthesis of glucosinolates, compounds that give mustard, horseradish and wasabi their characteristic flavors. Interested in how he could use genetics and the emerging model plant Arabidopsis thaliana to gain a better understanding of plant biochemistry, he moved on to a postdoctoral position with Dr. Chris Somerville at the Michigan State University Department of Energy Plant Research Laboratory in 1990.

A Distinguished Professor in the Department of Biochemistry, where he has been a faculty member since 1993, Dr. Chapple’s research now focuses on the analysis and manipulation of metabolic pathways in plants, with particular emphasis on Arabidopsis, using the tools of biochemistry, molecular biology and genetics. Dr. Chapple has received $8.7 million for his research program at Purdue University. He has published 57 papers and 17 reviews and book chapters and has given over 70 invited lectures at conferences and other universities. He was recognized as a Purdue University Faculty Scholar in 1999, won the Purdue University Agricultural Research Award in 2001 and the 2006-07 Richard L. Kohls Outstanding Undergraduate Teacher Award in the College of Agriculture. In 2002, he was named a Fellow of the American Association for the Advancement of Science. He has trained 13 graduate students, 11 postdoctoral fellows and takes particular pride in having given research experiences to over 40 Purdue undergraduates.

Abstract

Increasing awareness of the impact of global greenhouse gas emissions,dwindling petroleum reserves and concerns with regard to energy security have led to a dramatic increase in interest in the development of renewable, cellulose-based sources of biofuels. Lignin stands as a significant barrier to this goal because it interferes with the conversion of lignocellulosic biomass to fermentable sugars. Efforts aimed at decreasing lignin deposition show promise for improving biomass conversion efficiency, but considering that lignin is essential to plant viability, it is clear that novel approaches to the modification of lignin will be required to make efficient cellulose-based biofuel production a reality. One solution with significant promise takes advantage of the ability of the lignin biosynthetic machinery to accommodate a wide variety of input monomers, opening the door to the production of “designer lignins” that could support plant growth but be more readily removed post-harvest.

Research Accomplishments

Over the past 18 years, we have characterized mutants that are defective in the synthesis of sinapoylmalate, one of the major soluble phenylpropanoid secondary metabolites in Arabidopsis. In wild type, sinapoylmalate is accumulated in the upper leaf epidermis where it functions to absorb the UV light that accompanies the photosynthetically active wavelengths of light that plants depend upon. The character of this blue-fluorescent secondary metabolite can be exploited as a rapid method for isolating mutants defective in genes encoding enzymes or regulatory factors of the phenylpropanoid pathway. Mutants that lack sinapoylmalate can be readily identified by their red chlorophyll fluorescence under UV light among a population of blue f luorescent wild-type plants. Using this mutant screen, we have isolated a variety of mutants that have enabled us to clone genes of the phenylpropanoid pathway that have not previously been characterized. Surprisingly, these efforts have revealed that the phenylpropanoid pathway had been incorrectly drawn in textbooks for decades.

Biography

Professor of Horticulture and Landscape Architecture

Professor David E. Salt’s long-term research interest is to understand the function of the genes and gene networks that regulate the plant ionome (elemental composition), along with the evolutionary forces that shape this regulation. To achieve this, his laboratory couples high throughput elemental profiling with bioinformatics, genomics and genetics, biochemistry, and physiology in both genetic model species (yeast, Arabidopsis thaliana, and rice) and “wild” plants that hyperaccumulate various metals (Cd, Ni, and Zn), metalloids (As), and non-metals (Se) in their native habitat, including various Thlaspi, Pteris, and Astragalus species. Professor Salt has been involved in related work since his PhD (Liverpool University, UK, 1985–1988), working on the mechanisms of evolved copper tolerance in Mimulus gutattus (yellow monkey flower). He also has a BSc in Biochemistry (University of North Wales, Bangor, UK, 1981–1984) and an MSc in Computer Science (Hallam University, UK, 1984–1985), and has held faculty positions at Rutgers University (1993–1997), Northern Arizona University (1998–2001), and is currently a professor at Purdue University, where he has been since 2001. Professor Salt has published over 85 peer-reviewed papers with currently over 5,100 citations. Professor Salt has obtained over $15 million in competitive research awards, trained 17 postdoctoral researchers, and graduated four PhD students. Professor Salt has also been on the editorial board of five international science journals and was nominated by Nature Biotechnology as one of the “thought leaders and technology pioneers” in biotechnology in the past 10 years. Dr. Salt is also interested in informal science education, and the science-based interactive game he helped develop, the Genomics Digital Lab (GDL), recently won first prize (2008) in the Interactive Media Award sponsored by NSF and AAAS.

Abstract

Understanding how plants control their ionome, or mineral nutrient and trace element composition, will have an impact on agricultural resilience and productivity and on human health through improved nutrition. Ionomics uses systems biology approaches to couple high-throughput, multi-element quantification with genomics, genetics, biochemistry, and physiology to identify and characterize significant connections between a plant’s genome and its ionome. Using such an approach, we have uncovered specific genes, and networks of genes, that regulate and integrate a plant’s ionome during normal growth and development and in response to the environment. Further, associating changes in these genetic networks with the distribution on the natural landscape of individual plants is telling us how these plants adapt genetically to harsh environments, such as elevated soil salinity.

Research Accomplishments

The idea that mineral elements function as nutrients for plants is now taken for granted. However, this idea was still a matter of great scientific controversy 150 years ago and not codified until the late 1930s. Surprisingly, as recently as 1987 nickel was identified as an essential plant nutrient. The release of the DNA sequence of the first plant genome (Arabidopsis thaliana) in 2000 led to an explosion of discoveries by facilitating the application of genetic tools for the dissection of the mechanisms of fundamental biological processes. It was against this backdrop that David E. Salt and his coworkers had the original insight and vision to conceptualize that such genomic-scale biology could be used to study the mechanistic processes involved in plant mineral nutrition. The description of the mineral nutrient and trace element composition of an organism as the ionome arose from this work, and led to the new research paradigm that the ionome needs to be studied as an integrated whole. With funding from the National Science Foundation, the National Institutes of Health, and the state of Indiana, Salt implemented a system to study the ionome using high-throughput elemental analysis technologies integrated with both bioinformatic and genetic tools. With the solid conceptual framework of the ionome as a foundation and the implementation of a powerful experimental approach in place, Salt has gone on to publish a series of high-impact papers over the last five years that not only provide new biological insight into the mechanisms regulating the plant ionome, but also strongly validate the approach and original insight. Three of these papers involve the cloning and characterization of genes that underlie natural variation in the accumulation of cobalt, molybdenum, and sodium in A. thaliana, and a fourth paper for the first time dissects the molecular basis of how suberin in roots controls shoot accumulation of various elements including, calcium, zinc, and manganese.

This ionomics approach has also identified multiple other novel genes in A. thaliana involved in regulating accumulation of various elements, including potassium, sodium, calcium, iron, and molybdenum, which are currently being prepared for publication. To achieve this level of productivity, it was also critical that Salt was a pioneer in the use of DNA microarray technology to help map the physical location of mutations, allowing the rapid identification of ionomic loci in A. thaliana accessions with no existing genetic markers. In keeping with this early adoption of new genomic technologies, Salt has successfully applied genome-wide association analysis (GWA) for the identification of loci involved
in regulating the ionome. Using this information, Salt is now uncovering associations of natural variation in genes controlling life history traits such as sodium accumulation with the landscape distribution of plants, revealing the genetic architecture underlying specific adaptations to the environment. Salt has also gone on to also extend the ionomics concepts into yeast as a model cellular system and rice as an important crop, and through collaborations in C. elegans and mouse. Interwoven with the development of the biological and technological sides of ionomics, Salt has also displayed innovation in areas of storage and dissemination of the large datasets generated by the projects. By developing and deploying the ionomicsHUB (www.ionomicshub.org), Salt has now provided a mechanism to “open source” ionomic data and discovery. The ionomicsHUB is now delivering ionomics data (18–21 trace elements and mineral nutrients) on approximately 140,000 A. thaliana samples, 15,000 rice samples, and 52,000 yeast samples to over 4,107 unique users using 43 different languages in 932 cities in 78 countries and is being updated with new data regularly. In parallel with his efforts in the science of ionomics, Salt has also made major contributions in the dissemination of these ideas to the public. He has led the development of a 2,000-square-foot informal science exhibit on genomics called Genomics Explorer (www.genomicsexplorer.com ). This exhibit was recently on display at the Owensboro Museum of Science and History. Salt has also led a team in the development of the award-winning, sciencebased interactive game called the Genomics Digital Lab (GDL). This game won first prize in 2008 in the Interactive Media Award, Science and Engineering Visualization Challenge, sponsored by the NSF and the American Association for the Advancement of Science (AAAS), and in the World Summit Awards
e-Science & Technology, 2009. The game is currently distributed free of charge by the American Society of Plant Biologists (http://www.aspb.org/education/GDLProject.CFM).

Biography

Vladimir (Vlad) M. Shalaev, the Robert and Anne Burnett Professor of Electrical and Computer Engineering and Professor of Biomedical Engineering at Purdue University, specializes in nanophotonics, plasmonics, and optical metamaterials. He earned a doctoral degree in physics and mathematics in 1983 and a master’s degree in physics, with highest distinctions, in 1979, both from the Siberian Federal University (SFU) in Krasnoyarsk, Russia. Shalaev came to Purdue in 2001 after previously holding the position of the George W. Gardiner Professor of Physics at New Mexico State University. He also previously taught and conducted research at the SFU and the University of Toronto. Before arriving in Canada and the United States, Vlad Shalaev was a Humboldt Foundation Fellow at the University of Heidelberg in Germany and Paris-Sud University in France. Vlad Shalaev made pioneering contributions to the optics of fractal and percolation composites and to their applications for surface-enhanced Raman spectroscopy (SERS). At Purdue, his seminal research in the field of optical metamaterials and transformation optics resulted in several important breakthroughs, including the first experimental observation of a negative refractive index in the optical range, artificial magnetism across the entire visible range, and novel approaches for imaging with sub-wavelength resolution and optical cloaking.

Professor Shalaev has received several awards for his research in the fields of nanophotonics and metamaterials. He is a Fellow of the American Physical Society (APS), a Fellow of The International Society for Optical Engineering (SPIE), and a Fellow of the Optical Society of America (OSA). Professor Shalaev is an editor or co-editor for five books in the area of nanophotonics, is a program chair for a number of international symposia and conferences, and is co-editor and/or an editorial board member for eight research journals. In total, Vlad Shalaev has authored or co-authored three books, 21 invited book chapters and over 300 research publications.

Abstract

Transforming Light with Metamaterials: A New Paradigm for the Science of Light
One of the most unique properties of light is that it can package information into a signal of zero mass and propagate it at the ultimate speed. It is, however, a daunting challenge to bring photonic devices to the nanometer scale because of the fundamental diffraction limit. Metamaterials can focus light down to the nanoscale and thus enable a family of new nanophotonic devices. Metamaterials, i.e. artificial materials with rationally designed geometry, composition, and arrangement of nanostructured building blocks called meta-“atoms,” are expected to open a gateway to unprecedented electromagnetic properties and functionalities that are unattainable with naturally occurring materials. We review this exciting and emerging field and discuss the recent, significant progress in developing metamaterials for the optical part of the electromagnetic spectrum. Specifically, we describe the recently demonstrated phenomena of artificial magnetism across the whole visible and negative refractive indices in the optical range, and we discuss the promising approaches and central challenges in realizing optical cloaking. A new, powerful paradigm of engineering space for light with transformation optics will be also discussed.

Research Accomplishments

Vlad Shalaev is known world-wide for his pioneering contributions to nanophotonics, the optics of nanocomposites including fractals and percolation systems, and optical metamaterials. During the last seven years, the Shalaev research group has conducted many critical theoretical analyses and has accomplished nanofabrication and seminal experimental work on optical metamaterials that exhibit negative refractive indices and magnetic responses at optical frequencies.

In the optical range, the magnetic response (permeability) for naturally occurring materials is very close to its free space value, indicating that natural materials have almost no magnetic response at optical frequencies. Before the year 2004, the shortest wavelength at which materials exhibited a significant magnetic response was on the scale of millimeters. Since 2004, researchers from various groups have fabricated and experimentally demonstrated various metamaterials with magnetic responses at wavelengths from 300 micrometers down into the near-infrared. However, the Shalaev group was the first to demonstrate artificial magnetism across the entire visible range. As a result of these breakthroughs in the field, the frequency range for materials with magnetism has been expanded by five orders of magnitude.

In the year 2005, the Shalaev research group demonstrated the first optical metamaterial with a negative refractive index at the telecommunication wavelength of 1.5 µm. This was the breakthrough demonstration of a negative refractive index in the optical range. This pioneering work was based on Vlad Shalaev and his co-authors’ earlier (in 2002) theoretical prediction that pairs of metal nanorods can provide a negative refractive index, which is exactly the structure that the Shalaev group used to demonstrate their first negative-index optical metamaterial. Almost simultaneously, Professors S. Brueck and R. Osgood used a physically equivalent “fishnet” structure to demonstrate a negative refractive index at a wavelength of 2 µm. Later, Professor Wegener used the same structure to obtain a negative refraction index at 780 nm. Most recently, Professor Shalaev’s group has demonstrated a metamaterial with a negative refractive index for yellow light, at 580 nm, which is currently the shortest wavelength at which a negative refractive index has been observed for light.

The Shalaev group has further extended the possible applications of optical metamaterials by showing the feasibility of cloaking objects in the visible range. Vlad Shalaev’s proposal of cloaking in the visible part of the spectrum is original and different from that proposed earlier by Pendry, Smith, et al., which is suitable only for the microwave range. Later, Shalaev’s group also suggested a high-order transformation method for cloaking, which allows one to remove any residual scattering resulting from an impedance mismatch. Most recently, Vlad Shalaev and his group suggested the idea of “cascaded” cloaks operating at multiple wavelengths, thus potentially enabling broadband invisibility. Finally, the Shalaev and Smolyaninov groups have recently demonstrated broadband cloaking in a specially tapered waveguide, which emulates well the metamaterial-based anisotropic cloak and thus verifies the Shalaev group’s idea for cloaking. Currently, the Shalaev group is working on novel approaches for engineering and controlling space for light based on transformation optics, a new paradigm for the science of light which is expected to result in a family of new “meta-devices.”

Biography

Professor of Biological Sciences

Richard Kuhn completed his undergraduate studies in biochemistry at the State University of New York at Stony Brook. In 1981 he joined the Department of Microbiology where he did graduate research studying poliovirus replication in the laboratory of Dr. Eckard Wimmer. After receiving his PhD in molecular virology in 1986 he joined the laboratory of Dr. James Strauss at the California Institute of Technology. He was recruited to Purdue University as an assistant professor in the Markey Center for Structural Biology in 1991. He was appointed Head of the Department of Biological Sciences in 2005 and the Director of the Bindley Bioscience Center in 2007. His research at Purdue has focused on the replication and assembly of alphaviruses and flaviviruses. Together with his structural biology colleagues especially Michael Rossmann, he has been involved in many fundamental studies examining the structure and assembly of enveloped viruses, including the first structure of dengue virus. His focus continues to be in virus replication, virion assembly, pathogenesis, and host cell interactions using biochemical, genetic, and structural techniques. Professor Kuhn was elected a Fellow of the American Academy of Microbiology and the American Association for the Advancement of Science (2007), selected as a Purdue University Faculty Scholar (2004–2009) and is a member of the U.S. Panel on Viral Diseases of the US-Japan Cooperative Medical Sciences Program. He serves on the editorial boards of the Journal of Virology, and Virology, and is the author of over 100 publications.

Abstract

Pursuing Dengue Virus: A 21st Century Scourge
The flaviviruses are an important group of human pathogens that are found worldwide. They include members such as hepatitis C virus, yellow fever virus, West Nile virus, and dengue virus. Dengue has become the most important of the insect-transmitted human viruses, with 2 billion people at risk, and 50 million infections each year. The laboratory has focused on investigating the life cycle of the virus by the integration of structural, biochemical, and molecular genetic approaches. These analyses allow powerful ‘structure-function’ studies in which dissecting the atomic composition and layout of the virus and its components permits one to interpret how they work together to allow the virus to replicate. This talk will present an overview of the dengue virus life cycle and how we are closer to understanding this important human pathogen and developing new intervention strategies.

Research Accomplishments

Professor Kuhn’s major expertise is in the field of molecular virology. The application of his expertise in collaboration with laboratories in structural biology, using x-ray crystallography, NMR, and electron microscopy to analyze viruses and macromolecular structures, has created at Purdue University one of the very best, most productive, and best-known virus structure-function laboratories in the world. The collaborative mode of experimental research that describes the interactions of these individuals is characteristic of many of the best modern-day laboratories in the biological sciences.

The Kuhn laboratory is studying the molecular mechanisms involved in virus gene expression and the nature of virus-host interactions. An understanding of these two related areas is essential for a comprehensive model of virus pathogenesis and for a description of the molecular evolution of viruses. We have focused our attention on several groups of RNA-containing viruses that are important human pathogens. Many of these viruses are emerging into new regions of the world. Several specific areas of virus replication are under study: (1) the assembly of the virus particle; (2) molecular analyses of the structural proteins and their role in pathogenesis; (3) structure—function studies of replication proteins; and (4) the design of novel intervention strategies against enveloped viruses.

The laboratory is examining the assembly pathways for several enveloped animal viruses that are important human pathogens. The viruses being studied include Sindbis and Ross River, which are classified as alphaviruses, and hepatitis C, West Nile, dengue, and yellow fever, which are grouped into the flavivirus family. Our approach is to use biochemical, molecular genetic, and structural techniques to gain insight into the molecular requirements for particle formation. During the past several years, the laboratory has made significant progress in understanding alphavirus and flavivirus virion structure and assembly.

The Kuhn laboratory has also initiated an extensive structure-function analysis of the proteins found in the alphavirus and flavivirus groups. Our goal is to solve the atomic structure of all replication and virion proteins and to use that information to guide molecular genetic studies to understand how the proteins function and how that relates to pathogenesis. To this goal, the laboratory has established a variety of in vivo and in vitro systems for studying various aspects of virus replication. We have also established ‘replicon’ systems that allow us to study virus-host interactions without the complication of virus particles and repeated cycles of virus infection. These systems are also valuable for screening compounds for antiviral activity.

In collaboration with the Bindley Bioscience Center, the laboratory is exploring a global view of the effect of flavivirus replication on host gene expression. For these studies, data-intensive techniques are employed that include microarrays, proteomics and lipidomics analyses of flavivirus infected cells. This macroscale approach will be followed by a detailed analysis of virushost protein interactions that play a direct role in virulence and disease. The ultimate goal is to achieve an understanding of the relationship between the virus and its human host so that viral disease can be mitigated. Professor Richard Kuhn’s research is focused on the molecular mechanisms underlying virus biology—how viral genes are expressed, how viruses are assembled, and the molecular bases for virus-host interactions. Viruses come in many forms: some are enveloped in a lipid-protein membrane, and some are not enveloped; some are spherical, and others include long projections; some contain RNA (plus-stranded or minus-stranded), and others contain DNA. Richard specializes in two families of plus-strand spherical enveloped viruses, the togaviruses and flaviviruses. Richard’s lab has worked on several enveloped animal viruses that are important human pathogens, including Sindbis, Ross River, hepatitis C, yellow fever, Dengue, and West Nile.

Biography

Professor of Chemistry

Scott A. McLuckey earned a PhD degree in chemistry in 1982 from Purdue University. He subsequently spent one year as a visiting scientist at the FOM Institute for Atomic and Molecular Physics in Amsterdam. In late 1983, he joined the Analytical Chemistry Division of Oak Ridge National Laboratory (ORNL) as a Eugene P. Wigner Fellow. In January, 1990, he was named Head of the Analytical Spectroscopy Section and led the Organic and Biological Mass Spectrometry Group within the section. In January, 2000, McLuckey moved to Purdue as a professor of chemistry.

McLuckey’s research emphases have been placed in the areas of gasphase ion chemistry and instrumentation for organic and biological mass spectrometry. Fundamental aspects of ionization, unimolecular reactions, and bi-molecular reactions have been studied with the goal of improving the capabilities of analytical mass spectrometry. Attention has been focused on ionization by glow discharge, positrons, and electrospray. Ion activation, ion/molecule reactions, and ion/ion reactions have been major focal areas within the context of the mass spectrometry/mass spectrometry experiment. Instrumentation for tandem mass spectrometry has also been highlighted with emphasis on electrodynamic ion traps.

McLuckey was the inaugural winner of the Biemann Medal by the American Society for Mass Spectrometry (ASMS) in 1997. In 1999, he was named ORNL “Scientist of the Year”. In 2000, he won the Curt Brunneé Award from the International Mass Spectrometry Society. In 2007, he was awarded the American Chemical Society Division of Analytical Chemistry Award in Chemical Instrumentation. In 2008, he was the recipient of the Anachem Award from the Federation of Analytical Chemistry and Spectroscopy Societies. He has served as editor of the International Journal of Mass Spectrometry since 1997 and is currently vice president for programs and president-elect of the ASMS.

Abstract

Ion/Ion Reactions in the Gas Phase: New Chemistry for Bio-analysis
The advent of ionization methods that enable the formation of ions derived from large bio-molecules has revolutionized the practice of analytical mass spectrometry, which is making key contributions to modern molecular biology research. Historically, mass spectrometry has relied on gas-phase ion chemistry to provide ion structure information. For this reason, the gas-phase ion chemistry of bio-ions in mass spectrometers has been the subject of widespread investigation. A number of new developments in gas-phase bio-ion chemistry have taken place within the past decade that have played major parts in the rapidly expanding roles of mass spectrometry and tandem mass spectrometry in bio-analysis. This lecture relates these developments with particular emphasis on ion/ion reactions involving multiply charged ions, a class of chemical reactions being pioneered at Purdue.

Research Accomplishments

Emphasis in our laboratory is placed in the areas of gas-phase ion chemistry and instrumentation for organic and biological mass spectrometry. Fundamental aspects of ionization, unimolecular reactions, and bi-molecular reactions are studied with the goal of improving the capabilities of analytical mass spectrometry. Attention has been focused on ionization by glow discharge, positrons, and electrospray. Ion activation, ion/molecule reactions, and ion/ion reactions have been major focal areas within the context of the mass spectrometry/mass spectrometry experiment. Instrumentation for tandem mass spectrometry has also been highlighted with emphasis on electrodynamic ion traps and hybrid instruments that combine elements of ion trapping with ion transmission in a single experiment. Current research efforts are heavily directed towards relatively large polymeric species including peptides, proteins, oligonucleotides, and synthetic polymers. Fundamental studies are directed at issues regarding the structures and stabilities of gaseous ions formed from relatively large molecules. Information forthcoming from such studies is exploited for analytical chemistry R&D directed towards the analysis of, for example, protein mixtures, mixtures of small nucleic acids (typically RNA and DNA oligomers of less than 200 residues), and commercial polymers. Current projects include, for example, the development of novel methodologies for the identification and characterization of proteins in complex mixtures (i.e., proteomics), the characterization of small nucleic acids, and fundamental aspects of ion/ion reactions that underlie many of the novel methodologies.

The group’s activities can be summarized on the basis of three core emphasis areas. These include fundamental research in ion chemistry, the development of new tools, and applications of our group’s tools and chemical insights to analysis problems. These activities are synergistic. New chemical insights often enable new applications, analytical application problems often give rise to new fundamental ion chemistry questions, new instruments often enable new applications, important applications often drive the development of new instruments, and so on. Many projects often involve all three activities. These activities are inherently prone to serendipity, the process of finding things not sought. While it is difficult to plan discoveries, exploring new reactions with unique tools is a strategy that is amenable to discovery. Hence, the activities emphasized in the group constitute an intentional process to facilitate discovery. Perhaps the most interesting work performed by this group has evolved from unexpected findings. Hence, the group’s work involves both “pull” (i.e., work that is driven by the needs of particular problems) and “push” (i.e., work arising from unexpected findings that lead to unforeseen solutions to measurement problems). Ion/ion reaction research is an example of the latter scenario. The work initially was curiosity driven but evolved into a major part of the application effort of the group. Mass spectrometers designed for ion/ion reactions are now commercially available.

Biography

Joseph S. Francisco, Purdue University’s William E. Moore Distinguished Professor of Earth and Atmospheric Sciences and Chemistry, is the 2007 recipient of the Herbert Newby McCoy Award. The McCoy award was presented by President Martin Jischke on April 15 at the Annual Spring University Honors Convocation.

Comments from nominating letters include:

“Through the years, Professor Francisco has endeavored to apply new tools from theoretical and experimental physical chemistry to atmospheric chemical problems to bring about an understanding of the various chemical processes in the atmosphere at a molecular level. In fact, he was one of the first to realize the value of computational chemistry in elucidating atmospheric chemical mechanisms and in identifying new chemical species that play important roles in atmospheric chemical processes. This work has aided in the timely assessment of the environmental impact of new industrial materials and has provided critical information to assist in making informed decisions on the environmental impact of new industrial materials.”

“It is well known that chlorofluorocarbons (CFCs) threaten our environment by their depletion of the protective ozone layer in the stratosphere. Yet, CFCs have been so useful to society from refrigerants to cleaning agents. What compounds might take their place? It is in answering this question that Professor Francisco has made significant contributions to determining whether certain modified CFC replacements do not decompose ozone and do not contribute to the greenhouse gas burden.”

Francisco received his baccalaureate degree from the University of Texas at Austin, Texas and his Ph.D. in chemical physics from Massachusetts Institute of Technology in 1983. He also did postgraduate studies at Cambridge University in England as a Research Fellow and at Massachusetts Institute of Technology as a Provost Postdoctoral Fellow. In addition, Francisco has been the recipiant of a Presidential Young Investigator award, an Alfred P. Sloan Research Fellow award, a Camille and Henry Dreyfus Teacher-Scholar award, a John Simon Guggenheim award and an Alexander von Humboldt Senior U.S. Scientist award.

In the fall of 2007, Francisco will describe his work in detail at the Annual McCoy Distinguished Lecture. Following the lecture is the Annual McCoy Distinguished Recognition Dinner honoring all McCoy award winners. The date for these events will be announced in a future issue.

Biography

Supriyo Datta , Supriyo Datta, Purdue University’s Thomas Duncan Distinguished Professor of Electrical and Computer Engineering, is the 2006 recipient of the Herbert Newby McCoy Award. The McCoy award is presented annually for the most significant science contribution of the year at Purdue. The award will be presented on April 9 at the Annual Spring University Honors Convocation.

Professor Datta is recognized for his seminal scientific contributions to the theory of quantum transport in nanoscale electronic devices and molecular electronics. Datta’s interdisciplinary work on quantum mechanical transport spans chemistry, physics and electrical engineering and has produced: a sound, conceptual understanding of electronic conduction at the molecular scale; the first rigorous quantum simulations of nano- and molecular scale electronic devices; and the first concept for a spintronic switch (the so-called Datta-Das spin transistor) and more recently for a new kind of spin-based memory. His conceptual approach and computational methods are now widely-used by scientists and engineers throughout the world, and his ideas for spintronics focused international attention on the field.

Since the invention of the transistor in 1947, progress in electronics has occurred by shrinking the size of the basic device (transistor) and increasing the number of them on an integrated circuit ‘chip’. The critical dimensions of a transistor are now less than 50 nanometers (in the horizontal direction) and less than 2 nanometers in the vertical direction. (For reference, the diameter of a DNA double helix is about 2nm). This dramatic decrease in physical dimensions has created the need for new and improved theories to deal with the implications of electronics devices of these dimensions.

Through his books, seminars, tutorials, short courses, and full courses at Purdue and online, Supriyo Datta’s ideas are shaping the future of electronic devices. His books and papers on these topics have been cited 5,945 times.

Professor Datta received his BTech degree from the Indian Institute of Technology and his MS and PhD degrees from the University of Illinois where he was a visiting assistant professor until joining Purdue in 1981. He was named the Thomas Duncan Distinguished Professor in Electrical and Computer Engineering in 1999. He is also the director of the NASA Institute for Nanoelectronics and Computing.

In the fall of 2006, Datta will describe his work in detail at the Annual McCoy Distinguished Lecture. Following the lecture is the Annual McCoy Distinguished Recognition Dinner honoring all McCoy award winners, with the date for these events to be announced.

Biography

David D Nolte , David D. Nolte, professor of physics, has been a member of the Purdue University Faculty since 1989. A native of northern Ohio, he attended Cornell University in Ithaca, NY where he worked summers at the Cornell electron storage ring (CESR) helping build and analyze data from the CLEO particle detector just after CLEO began operating in 1980. He was deeply influenced by professors Al Sievers and Kurt Gottfried and future Nobel prize winners David Lee and Robert Richardson. He graduated Phi Beta Kappa in 1981 with a B. A. degree from the School of Arts and Sciences.

After Cornell, with the help of Gottfried and David Cassel, he received a summer fellowship from the German Academic Exchange Program (DAAD) to work at the German electron synchrotron (DESY) on the PETRA ring outside of Hamburg. He worked with the group of Professor Hermann Fischer from the University of Bonn on two-photon events that occur when an electron and positron each emit a photon under low-angle scattering. The photons are so energetic that they collide and generate a particle-antiparticle pair. These interacting photon events interestingly presaged his later work in nonlinear optics where photons interact with photons inside crystals but with energies a billion times smaller .

After Hamburg, Nolte entered graduate school in physics at the University of California at Berkeley and took his first research position under Professor Paul Richards helping build a rocket-borne infrared spectrometer to study the cosmic background radiation left over from the Big Bang. While working in Richard’s infrared lab, he was attracted to the research of students working for Prof. Eugene Haller on defect states in semiconductors. In 1983, he switched research fields to work in solid state physics under the direction of Haller and Prof. Leo Falicov. He graduated from Berkeley with his PhD in 1988.

Nolte took a post-doctoral position at AT&T Bell Laboratories in Holmdel, NJ under the direction of Alastair Glass. There he was introduced to the field of laser physics and quantum electronics, and in particular to a nonlinear optical process known as the photorefractive effect in which photons interact with other photons under extremely low light conditions. While working with Glass, Wayne Knox and Daniel Chemla, Nolte demonstrated the first photorefractive quantum well (PRQW) structures in the summer of 1989.

In the fall of 1989, Nolte took a position as an assistant professor in the physics department at Purdue University where he continued working on photorefractive effects in semiconductors and established a new record in 1990 with the PRQW devices for the highest-sensitivity dynamic holographic effects in any material system. Through the 1990’s Nolte’s group explored the origins of the high sensitivity, uncovering novel nonlinear transport effects in highly-compensated semiconductor quantum structures. During this time Nolte also explored quantum confinement effects in quantum structures, performed the first magneto-optic time-reversal experiments, studied femtosecond optical interactions using holography, and began applying the sensitive holographic devices to applications such as adaptive interferometry, femtosecond pulse manipulation and biomedical applications, including the invention and demonstration of the BioCD.

Nolte is co-author or author of more than 140 publications and holds 6 patents in optoelectronic materials and interferometry. He has written numerous book chapters and encyclopedia articles, has been editor of 4 volumes and is the author of the book “Mind at Light Speed: A New Kind of Intelligence” (Simon&Schuster, 2001). He is a fellow of the American Physical Society (APS) and the Optical Society of America (OSA). He was a Presidential Young Investigator (PYI) of the National Science Foundation and a research fellow of the Alfred P. Sloan Foundation, and is a Purdue University Faculty Scholar. He is a dedicated teacher and received the Ruth and Joel Spira Award for best undergraduate teacher in physics. His past and present outside activities include serving as member of the board of advisors for Nankai University in Tianjin, China, technical founder and member of the scientific board of the Lafayette-based company QuadraSpec, Inc., NATO science consultant, chairman of the 8 th International Conference on Photorefractive Effects and Materials, and he has served for numerous years on the technical committee of the conference on lasers and electro-optics (CLEO).

Research Accomplishments

Dynamic holography uses light to control light, just like transistors use electrons to control other electrons. In dynamic holographic mixing, two laser beams form mutual interactions in a nonlinear medium that allows the light beams to self-diffract off each other. The world’s most sensitive dynamic holographic material is the photorefractive quantum well (PRQW) developed by Nolte at Purdue in collaboration with Prof. Michael Melloch of the School of Electrical Engineering. The special importance of the PRQW devices is the unusually low light levels that can still accomplish this self-scattering of light off light. Fully-developed holograms can be recorded in the PRQW devices using laser light as dim as the light of a darkened room.

The superior properties of these advanced optoelectronic materials are based on unexpected physics of electronic transport that, in effect, put electrons in suspended animation inside semiconductor crystals under high electric field. Dielectric relaxation, that normally limits charge accumulation in semiconductors, is disabled under high electric fields in these highly-compensated materials, thus allowing low light intensities to drive large charge redistribution. This nonlinear electron transport gives the materials exquisite sensitivity to record extremely weak light fluxes.

Nolte’s group has recently achieved a landmark accomplishment that spans the fields of holography and biomedical imaging by using these media to record the first depth-resolved holograms of biological tissue, imaging into rat osteogenic sarcoma tumor spheroids and mouse corneas. In this application, dynamic holography acts as coherent “sun glasses” that eliminate the glare of scattered light that normally makes it impossible to see into skin and tissue. With this adaptive optics approach, it is now possible to peer directly inside translucent media using neither ionizing radiation nor computed reconstruction. This work represents a paradigm shift both in the fields of holography and in biomedical imaging—the first time such weak holograms have been recorded in fast dynamic media, and the first time it has been possible to use light to see directly inside tissue.

The idea of using light to image into biological tissue has a long history motivated by its benign nature compared to potentially hazardous X-rays, and its high spatial resolution compared to MRI technology. While a vigorous community of optical biomedical imaging has emerged, none of the standard optical techniques had allowed direct depth-resolved imaging, requiring instead computed tomography, model-based signal inversion, diffusing photons, or point-by-point scanning. Within the holography community, many attempts had been made, with some success, to see through tissue, essentially by shadow-casting to generate 2D projections. But none had been able to record holograms in reflection, from selected depths, allowing full 3D viewing. First proposed in 1963, only 3 years after the invention of the laser, volumetric holographic imaging into living tissue was an unfulfilled dream for almost 40 years This is because light scattered from deep inside biological tissue is exceedingly weak, dimmer by up to 8 orders of magnitude relative to background intensities (the glare that keeps us from seeing into our skin). Only by the unique sensitivity of the PRQW materials is it possible to record holograms of such weak signals, thereby establishing the Purdue group of David Nolte, in collaboration with Prof. John Turek of the Veterinary School of Medicine, as the first to accomplish the goal of direct holographic biomedical imaging.

There is an unusual breadth to Nolte’s research activities. Tangential to the biomedical imaging research, he has studied the physics and applications of optical time reversal. He was the first to explore the fundamental physics of time-reversed light in the presence of magnetic fields, with the help of Prof. Ramdas and Dr. Miotkowski of the Physics Department, and the first to apply femtosecond spectral interferometry, in collaboration with Prof. Andrew Weiner of the School of Electrical Engineering, to cause photons to jump forwards and backwards through time. He also has an active collaboration in geophysics with Prof. Laura Pyrak-Nolte of the Physics Department, making contributions to seismic imaging of fractures, and participates in fundamental explorations of the physics of fluids in micron-scale porous media.

Nolte has built one of the world’s most sensitive adaptive interferometers. It uses adaptive holography to compensate mechanical variations and optical aberrations that plague all current conventional interferometers. The mirrors of the adaptive interferometer can move by tens of microns, yet the interferometer has achieved surface displacement sensitivity to less than a picometer. The ability to perform vibration-free interferometry is a powerful and widely applicable resource for the field of sensing and metrology. His group is now applying this concept to their newly-developed BioCD, a biochip implemented as a spinning-disk interferometer that detects molecular recognition of antibody-antigen binding. The BioCD has been licensed by Purdue University to QuadraSpec, Inc. of Indiana, which recently won the prestigious Krannert-sponsored 2004 Burton T. Morgan Entrepreneurial Competition based on David’s technology and his collaboration with Prof. Fred Regnier of the Chemistry Department. The BioCDs have the potential for high-speed high-throughput molecular assays with applications in diagnostic medicine and drug discovery.

Abstract

From Holographic Semiconductors to Your State of Health
A long-term goal of photonic research is the control of light by light inside nonlinear optical materials just like electrons control electrons inside transistors. However, unlike charged electrons that interact and repel strongly, light does not naturally interact with itself. Indeed, one of the great advantages of using light for communications is that light beams pass entirely through each other without any effect at all. But inside nonlinear optical crystals, light uses the electronic properties of the intervening material to mediate an indirect interaction between photons. While this secondary interaction is usually extremely weak and requires laser intensities brighter than the surface of the sun, our research group in the Department of Physics has developed a material, based on quantum effects in semiconductors, that allows photons effectively to bounce off of other photons with 40% efficiency using light that is as dim as the light in a darkened room.

With this extraordinarily sensitive material, fashioned into devices called photorefractive quantum wells (PRQW), we recently achieved the long-standing goal of holographic imaging into living tissue. Proposed over 40 years ago, shortly after the invention of the laser, we were the first to image inside living tissue, observing morphological structure inside osteogenic cancer tumors and tracking the time course of a toxin affecting mitochondrial electron transport by measuring sub-cellular motility in the form of shimmering laser speckle.

Perhaps the most ubiquitous application of the holographic films is in adaptive interferometry, which we have applied to ultrasound detection, with potential for non-contact biomedical imaging. More recently, we have applied it to the detection of proteins on spinning disks called BioCDs. The BioCD uses concepts borrowed from music compact discs (CDs), but we modify them to sense proteins in samples with high sensitivity and at high speed. The rim of the BioCD spins at velocities up to 60 mph making protein measurements at a rate of up to a million per second. The high-capacity potential of the BioCD may one day make it possible to track concentrations of thousands of proteins in blood to define a molecular state of health that is like a trajectory through a high-dimensional “health” space.

Biography

Stanton B. Gelvin, professor of biological sciences, has been a Purdue University faculty member since 1981. Born in New York City, he grew up in New Jersey, and received his AB degree in biology from Columbia University in 1970. He went on to attend Yale University, where he received his MPhil degree in 1973 from the Department of Molecular Biophysics and Biochemistry.

After transferring to the University of California, San Diego, he was introduced to the study of plant molecular biology by his doctoral advisor, Dr. Stephen H. Howell. He received his PhD in biology from USCD in 1977, where he isolated and characterized the first non-ribosomal gene from plants, the chloroplast gene encoding the large subunit of the key photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase from the unicellular green alga Chlamydomonas reinhardtii. Gelvin spent another year in Howell’s laboratory as a postdoctoral research fellow investigating unusual repetitive DNA structures in Chlamydomonas chloroplast DNA.

Gelvin subsequently moved to the University of Washington, Seattle, where he worked as a Damon Runyon-Walter Winchell fellow in the laboratories of Drs. Eugene W. Nester and Milton P. Gordon. It was in these laboratories that Gelvin was introduced to the Agrobacterium tumefaciens system, a system that he has continued to investigate for the past 25 years.

Gelvin joined the faculty of Purdue’s Department of Biological Sciences as an assistant professor in 1981 and has investigated a number of aspects of the Agrobacterium-plant interaction. His early work involved an elucidation of transcriptional activating elements of several Agrobacterium T-DNA genes; this work culminated in the development of the “super-promoter,” a strong constitutive promoter that has been used by hundreds of academic and industrial scientists to express genes in transgenic plants. After several years investigating the molecular and genetic mechanisms of Agrobacterium virulence gene induction, Gelvin turned approximately 10 years ago to his current line of investigation, the identification and characterization of plant genes and proteins involved in Agrobacterium-mediated plant genetic transformation. Gelvin was promoted to full professor in 1991; he currently also is an adjunct professor at the Institute of Botany, Academia Sinica, Taipei, Taiwan.

Early in his career at Purdue, Gelvin was selected as a NSF Presidential Young Investigator. He holds five patents and has authored more than 100 publications, including editing a widely used laboratory techniques manual on plant molecular biology. He has been a frequent organizer of the national annual Crown Gall Conferences, and has organized numerous workshops and sessions at international meetings.

Gelvin has served as associate editor for the journals Plant Molecular Biology and Molecular Plant-Microbe Interactions (MPMI), and is a past editor-in-chief of MPMI. He has served on numerous USDA grant review panels and was panel director for the USDA IFAFS panel in 2000. He has been director of the interdisciplinary Purdue Genetics Program since 1999, and was instrumental in initiating and developing the new PULSe interdisciplinary life sciences graduate program.

In his spare time, Gelvin enjoys playing clarinet with the Lafayette Citizens Band and the Lafayette Civic Theater musical productions, gardening with his wife and scientific colleague Dr. Lan-Ying Lee, and playing with his model electric trains.

Research Accomplishments

Agrobacterium tumefaciens, and the related species A. rhizogenes, A. vitis, and A. rubi, cause neoplastic diseases on a wide range of plant species. The molecular mechanism by which Agrobacterium transforms cells involves the transfer of a segment of DNA, the T-(transferred) DNA, from a resident plasmid to the host genome. This horizontal gene transfer between species of different phylogenetic kingdoms is unique in nature, but is an extension of intra-kingdom DNA exchange (conjugation) commonly seen among bacteria. Recently, scientists have learned that this “DNA exchange” really represents “protein exchange” between species; proteins are transferred between organisms using what is known as a Type IV secretion system, with the consequence that DNA linked to these transferred proteins is also exchanged. An identical mechanism of protein transfer is used by many human and animal pathogens, including Bordetella pertusis, Legionella pneumophila, Helicobacter pylori, and various Brucella and Bartonella species, to transfer virulence factors to host mammalian cells. Agrobacterium has become the “model system” to investigate this type of protein transfer from these animal pathogens.

Once inside the host, T-DNA and the associated Virulence (Vir) proteins must traffic through the plant cytoplasm and target the nucleus, where Vir proteins are eventually stripped from the T-DNA and the T-DNA integrates into the host genome, thereby stably genetically transforming the eukaryotic cell. As a result of three decades of intensive investigation by numerous laboratories, scientists now have a reasonably complete understanding of the events that occur within the bacterium to initiate the transformation process. However, until very recently our knowledge of the events that transpire within the host and the contribution of host genes and proteins to this process have remained a mystery. My laboratory has contributed to understanding these latter events.

For the past decade, we have utilized several different approaches to understand the host contribution to Agrobacterium-mediated genetic transformation. The first approach is a “classical” forward genetic screen for plant mutants that are resistant to transformation. Using the model plant species Arabidopsis thaliana, we have identified more than 125 mutants that are resistant to Agrobacterium transformation (rat mutants), and more recently, mutants that are hyper-susceptible to Agrobacterium transformation (hat mutants).

We (along with our international collaborators) have characterized mutants that are defective in each of the steps of transformation. These include mutants defective in bacterial attachment to the plant cell (including plant cell wall synthesis and structural protein mutants), T-DNA and Vir protein transfer (including mutants lacking a putative receptor for the Agrobacterium T-[transfer] pilus), cytoplasmic trafficking (actin mutants), nuclear targeting (importin a and transportin mutants), Vir protein degradation (mutants of the 26S proteosome), T-DNA integration (various histone and chromatin protein mutants), and T-DNA expression (a histone mutant). Interestingly, the vast majority of these mutants have no obvious visible developmental phenotype; the plants appear completely normal. However, Agrobacterium is able to distinguish the loss of minor or partially redundant host proteins.

Although “forward genetics” is a powerful tool for investigating gene function, this methodology has limitations. We have, therefore, additionally employed a variety of “reverse genetic” and bioinformatic approaches to understand Agrobacterium-mediated plant transformation. “Forward genetics” starts with a mutant phenotype (the visible characteristics of an organism resulting from the interaction between its genetic makeup and the environment), from which scientists deduce the nature of the genetic lesion. “Reverse genetics” uses the opposite approach: Scientists start with a lesion in a known gene, following which they test the mutant organism for a specific phenotype. We have utilized several different reverse genetic approaches to define plant genes involved in Agrobacterium-mediated transformation. These include PCR-based reverse genetic screens, the use of anti-sense RNA and RNA inhibition (RNAi) technologies, and the use of yeast two-hybrid and in vitro systems to investigate the interaction of Agrobacterium Vir proteins and plant proteins.

We have recently been involved in a multi-laboratory project to develop a plant protein-protein interaction assay system. Taken together, these approaches allowed us to identify and characterize numerous plant proteins that can interact with Vir proteins. Most of these host proteins belong to “families” of highly related proteins. In many instances, mutation of the plant genes encoding these proteins resulted in a loss of transformation competence of the host. Thus, Agrobacterium is able to “pick out” specific members of multi-gene families and use these specific proteins to effect transformation.

Finally, we have used bioinformatic, macroarray, and microarray experimental approaches to identify, on a more global scale, plant genes that respond to Agrobacterium infection. We investigated the nature and kinetics of the response of plant cells to Agrobacterium cells during the first hours of interaction. Several hundred plant genes are either up- or down-regulated during this initial period, and the nature of the plant response depends on the strain of Agrobacterium that the plant cells see. Some plant genes respond to any Agrobacterium strain, whether virulent or avirulent, whereas other plant genes respond only to virulent strains that can transfer T-DNA and Vir proteins. Interestingly, Agrobacterium appears to manipulate plant gene response for its own advantage: The bacterium induces plant genes necessary for transformation and at the same time represses plant defense- and stress-response genes. Thus, Agrobacterium actively suppresses the plant’s defense system while simultaneously making the plant a more suitable host for transformation.

Abstract

The Molecular Mechanism of Plant Genetic Transformation by Agrobacterium tumefaciens, Nature’s Genetic Engineer
Agrobacterium tumefaciens is a soil bacterium that causes the neoplastic disease Crown Gall on hundreds of plant species. Agrobacterium is also nature’s genetic engineer. All virulent strains of Agrobacterium harbor a large extra-chromosomal segment of DNA called the Ti- (tumor inducing-) plasmid. During the course of infection, a small region of the Ti-plasmid, termed the T- (transferred-) DNA, is processed from this plasmid and transferred, along with several Virulence (Vir) proteins, from the bacterium to the plant. Once in the plant cell, the T-DNA must traverse the cytoplasm, enter the nucleus, and integrate into the plant genome. Following integration, T-DNA-encoded genes are stably expressed using the host’s transcriptional and translational machinery. Expression of oncogenes from the T-DNA results in over-production of plant growth regulating hormones, the auxins and cytokinins, causing unregulated plant cell growth and, consequently, tumors.

Several genes within the T-DNA also encode enzymes that direct the synthesis of novel low molecular weight compounds, termed opines. Opines can be used as carbon and (sometimes) nitrogen sources for the inciting bacterium to the exclusion of most other soil microorganisms. Thus, Agrobacterium genetically engineers plants to synthesize compounds, the opines, by which it can successfully compete with other organisms in the rhizosphere. Agrobacterium remains the sole known example of natural trans-kingdom (prokaryote to eukaryote) genetic exchange.

Approximately 20 years ago, scientists learned how to “tame” Agrobacterium for use as a genetic engineering organism for plants and, more recently, fungi and human cells. By deleting the oncogenes from the T-DNA, they “disarmed” the bacterium so that it would no longer produce tumors. However, these engineered laboratory strains could still deliver (non-oncogenic) T-DNA to plants, fungi, or mammalian cells. Any DNA segment now incorporated into the T-DNA would likewise be introduced into the host cell. The ability to deliver new genes into plants has formed the basis for modern agricultural biotechnology, resulting in plants resistant to herbicides and pathogens, plants with altered growth, metabolic, and nutritional characteristics, and plants that can be used as “bioreactors” to synthesize valuable pharmaceuticals and antibodies.

Although Agrobacterium-mediated plant transformation has provided a mainstay for plant biotechnology and plant molecular biology studies, many agriculturally important plant species, including corn, soybeans, cotton, fruit trees, trees used for lumber and pulp production, and ornamentals, remain highly recalcitrant to this method of transformation. To some extent, genetic manipulation of the bacterium has resulted in strains with a broader host range. However, major limitations for the use of Agrobacterium still remain. More recently, many scientists have concluded that we may be approaching the limits of our ability to manipulate the bacterium to improve its virulence, and that further success in broadening the host range may lie in an understanding and manipulation of the plant host. Our laboratory has become actively involved in understanding the role of host genes and proteins in the transformation process.

Through a broad range of experimental approaches and international collaborations, we have now identified more than 125 plant genes involved in Agrobacterium-mediated genetic transformation. These approaches have defined numerous host proteins contributing to each of the stages of transformation: bacterial attachment to the host cell, T-DNA and Vir protein transfer, cytoplasmic trafficking of the T-DNA and the associated Vir proteins, nuclear targeting of the T-DNA/Vir protein complex, removal of Vir proteins from the T-DNA, T-DNA integration into the host genome, and T-DNA gene expression. I shall present an overview of what we have learned about the host contributions to the transformation process. This knowledge will likely be applicable to human and animal pathogenesis.

Biography

Phil Fuchs, professor of chemistry, has been a member of the Purdue University faculty since 1973. Born in Milwaukee, Wisconsin, he grew up near the town of Nashotah (population 237) on an isthmus of land between Okauchee and Garvin lakes. During his grade school years Fuchs’ major summer activity was building a shack with his cousins. The ultimate edifice featured three rooms with a patio, a lake view from the top of a hill, screened windows, waterproof roofs, and a gabled kitchen complete with sink, tiled floor, furniture, and a custom-built icebox.

The majority of Phil’s grade school education took place in the four-room, Pine Lake Elementary School in Nashotah. Among his schoolmates was an exceptionally bright girl who constantly vexed Fuchs in matters educational. Her name was Diane. In the course of time, a grudging respect evolved, and Diane was allowed the use of Fuchs’ baseball glove. In 1959, eighth grade graduation saw the stage decorated in a scientific theme complete with a Fuchs-built Boron atom complete with tubing orbitals and Styrofoam electrons. Fuchs’ secondary education took place at Arrowhead High School in Hartland, Wisconsin. At the end of his sophomore year, he and another chemophile, Richard Pariza, decided to renovate an old out-building at the Pariza farm. At the end of that summer, the renovation yielded a laboratory named Willow Brook Laboratory, or WBL. It included epoxy-top lab benches and a homemade fume hood.

During the next two years, the two neophyte chemists purchased a virtually complete pre-lanthanide selection of the periodic table and performed reactions from the literature of organic and inorganic synthesis. Fuchs then attended the University of Wisconsin at Madison, enrolled in a program that allowed 65 of 130 credits to be chemistry. He rounded out his education with physics, math, history (of chemistry), a glassblowing class, and other required humanities. Throughout this enjoyable period, he performed undergraduate research and took five graduate classes in addition to regularly sharpening his statistical skills around the poker table.

While attending UW, Fuchs continued summer projects at WBL, selling reagents to Aldrich Chemical Company in Milwaukee and eventually advertising its chemicals on the back page of the Journal of the American Chemical Society. After receiving his undergraduate degree at the University of Wisconsin in 1968, Fuchs began graduate studies there with Edwin Vedejs. This was followed by a two-year postdoctoral fellowship at Harvard University with E. J. Corey (Nobel Laureate, 1990). Fuchs’ non-chemical accomplishments during this time included being on a winning tournament-bridge team, and once defeating the reigning Harvard summer chess champion.

Fuchs began his career at Purdue in 1973. Since that time, he has graduated an extended family of 55 Ph.D.s. His awards and honors include an Eli Lilly young faculty fellowship (1975), an Alfred P. Sloan fellowship (1977), a Pioneer in Laboratory Robotics award (1986), a Martin teaching award (1991), and being voted by the students as one of Top 10 Teachers in School of Science at Purdue (1991, 1993, 1995, 1996). Fuchs has consulted for Pfizer, and Eli Lilly, served on the editorial board of The Journal of Organic Chemistry, and is currently an executive editor for the Electronic Encyclopedia of Organic Reagents (eEROS), an online dynamic encyclopedia sponsored by John Wiley.

Research Accomplishments

Individuals who seek to synthesize meaningful quantities of chemicals face a universal material supply problem: The longer the synthetic route, the more material will be lost through less-than-quantitative reactions. For example, if one considers a linear sequence where the product of reaction 1 is the starting material for reaction 2, etc., and a total of five reactions are conducted, the overall yield will be Y1xY2xY3xY4xY5. Our study of the synthetic organic literature reveal that the best syntheses average 80 percent yield per operation; this means the hypothetical example would have an overall yield of 33 percent. An added consequence of inefficient syntheses is that the expense of disposing of unwanted by-products may often exceed the cost of producing the desired target material.

A constant theme in Fuchs’ research has been directed toward applying emerging technology as an adjuvant to organic synthesis. This included using the Radio Shack TRS-80 computer with four disk drives to initially store the ‘cutting edge’ total of 1 megabyte of literature citation data. The original program has long since been transported to our Macintosh network and now tracks over 40,000 literature references as well as the group chemical stockroom/archive. Another chapter in the fight for synthetic efficiency involved the integration of laboratory robotics and computers with Purdue-designed and built intelligent workstations for unattended optimization of organic reactions. Fuchs’ 1984 paper on this subject (J. Amer. Chem. Soc. 1984, 106, 7143-7145) predated the combinatorial chemistry revolution by five years. More recently, Fuchs has addressed the theoretical basis for designing organic synthesis.

Synthetic organic chemists are often accused of sharing a common heritage with used car salespersons. Both groups of individuals extol the virtues of their product but ignore or actively obfuscate areas of information that cast less favorable light on their wares. Guidelines that correlate the operational length of a synthesis with the structural intricacy of the target and starting material, can provide focus for the synthetic planner. Such discipline fosters aggressive new chemistry and can engender graceful and efficient access to the target. In conjunction with teaching his graduate synthesis class, Fuchs published a Tetrahedron paper in 2001 on the subject of “increase in intricacy” as a measure of the quality of an organic synthesis. The premise is that intricacy consists of stereocenters prochiral centers and rings, aryl-Z bonds, and heteroatoms. Weighting factors are not required since the intricacy factors are chemically interconvertible. Introduction of these attributes during the synthesis is a ‘value-added’ operation, provided that these features are created by the chemistry rather that simply being attached as preformed segments.

The consequences of paying attention to intricacy factors will be discussed throughout the seminar. For example, the first synthesis of the extraordinarily potent anticancer agent cephalostatin 1 began with two molecules of the inexpensive steroid hecogenin acetate, but employed a questionable strategy wherein atoms were initially excised from the molecule to enable further chemistry. Inspired by the intricacy equation, a fundamentally different approach to 1 is discussed where all atoms are retained, and new oxidative processes are invented as needed.

Abstract

Chemistry, Computers, and Cancer
The earth’s closed ecosystem is continually assaulted by an increasing array of chemical, biological, and population stresses resulting in consequences that demand scientific remediation. All the while, nature presents an abundant cornucopia of substances whose biological and structural information often proves crucial for drug development. Science and medicine are allies in the two-fold battle of deciphering and eradicating diseases that challenge human existence. Evaluation and development of drugs, including anticancer agents, involves a sequence of increasingly demanding scientific hurdles that a potential agent must exceed. Most of these toxic compounds are excluded from the candidate group because they do not strongly discriminate between cancer cells and healthy cells. The small group of compounds remaining continues to be aggressively culled as animal trials and preliminary trials with healthy humans reveal unacceptable properties. New natural and ‘unnatural’ products will continue to be subjected to this arduous procedure, but with odds of around 1-3/10,000, it is clear that new approaches are required. The use of computer-based modeling, in conjunction with synthetic efficiency analysis will be discussed in the context of teaming up with nature to attack the cancer problem.

Biography

Janet L. Smith, Professor Department of Biological Sciences was presented the prestigious Herbert Newby McCoy Award during the University Honors Convocation held April 14, 2001, for contributions to science for her research on protein three-dimensional structure and biological function.

Janet L. Smith is Professor of Biological Sciences at Purdue University, where she has been a member of the faculty since 1987.

A native of Pennsylvania, Smith studied chemistry as a National Merit Scholar at Indiana University of Pennsylvania (BS, 1973). Finding biochemistry to be the most stimulating area of chemistry, she continued her study in that field at the University of Wisconsin-Madison (Ph.D., 1978) where she was convinced of the importance of structure in biology by her research advisor M. Sundaralingam.

After her thesis research on crystal structures of protein synthesis inhibitors, Smith pursued a growing interest in protein structure by joining Wayne Hendrickson at the Naval Research Laboratory as a National Research Council Research Fellow. Following this postdoctoral work, she held positions as associate research scientist in Hendrickson lab and as associate research scientist at the Howard Hughes Medical Institute, both at Columbia University. Smith established a research program in structural biology at Purdue in 1987. She has been a visiting scientist at the European Molecular Biology Laboratory and the European Synchrotron Radiation Facility in Grenoble, France, and a lecturer at numerous international schools on structural biology and synchrotron radiation.

Smith’s research focuses on understanding biological processes through knowledge of the structures of key protein molecules. She has made major contributions to the understanding of catalysis and regulation in glutamine amidotransferases and phosphoribosyltransferases by solving and interpreting crystal structures of several enzymes of each type. She has solved crystal structures of photosynthetic proteins, leading to a new understanding of their function. She has also contributed to the development of methods for rapid determination of protein crystal structures, particularly using synchrotron X-ray sources.

Smith is co-author or author of more than 70 publications, and has served on the editorial boards of four journals: Current Opinion in Structural Biology, Macromolecular Structures, Protein Science, and Structure. She is a recipient of an National Institutes of Health (NIH) MERIT (Method to Extend Research in Time) Award for her work on understanding the function and structure of complex enzymes.

Smith holds membership in several scientific societies and has served on numerous on grant review panels. From 1996 to 1998, she chaired the Biophysical Chemistry Study Section A at NIH. She is a founder and the current chairperson of the Structural Biology Synchrotron Users Organization. She also served on the Department of Energy’s Biological and Environmental Research Advisory Committee and is a frequent advisor to synchrotron radiation facilities and synchrotron structural biology labs both in the U.S. and abroad. Smith is director of the NIH Collaborative Access Team for National Institute of General Medical Sciences and the NIH National Cancer Institute at the Advanced Photon Source, Argonne National Laboratory.

Research Accomplishments

Form determines function in biology, even at the level of individual molecules. The understanding of biological function derived from three-dimensional structures of key proteins is one of the most stunning outcomes of the molecular revolution in biology, which began with the realization that DNA codes for RNA, and RNA codes for protein. Proteins are the chemical machines of living systems; they are the control, communication and molecular transportation molecules of cells; and they form part of the structural skeleton. All proteins in an organism can be identified from its genome sequence, a parts list, as it were, for the chemical, regulatory, transport and communications systems of the organism. Genome sequences also provide linear amino-acid sequences for the set of proteins encoded in the genome. However, the three-dimensional structure – the unique “fold” of the polypeptide chain – must be known to understand the function and mechanism of a protein. The sequence of amino acids determines the fold of a protein, but at present the fold cannot be deduced from the amino acid sequence. Protein folds must be determined experimentally.

The overall goal of our research is to understand biological function at the molecular level through knowledge of protein three-dimensional structure. X-ray crystallography is the experimental method we use to determine protein structures. We have contributed to the development of new methods for rapid structure determination so that knowledge of key protein structures influences the study of biological problems early rather than retrospectively. This work takes advantage of powerful synchrotron X-ray sources, which are both tunable and extremely intense relative to conventional laboratory sources. The new methodology, multiwavelength anomalous diffraction (MAD), exploits the tunability of synchrotron sources to determine protein crystal structures rapidly and directly. Several years ago we demonstrated the broad applicability of the MAD method by showing that it can be used to solve crystal structures of large proteins. MAD is now used routinely, the method of choice for structure determination for us and many others.

Even though we can now determine protein structures rapidly, it is not possible to solve structures for all proteins that are relevant to all important biological processes. Therefore, a major application of protein structure information is to predict the function or molecular mechanism of other proteins. This is possible because Nature repeats successful molecular solutions to biological problems by gene duplication and adaptation of the duplicate copy to new function. A theme throughout our work has been to transfer the understanding of molecular mechanism of the proteins we study to other proteins.

One of the biological systems we study illustrates the sophisticated control mechanisms that balance the many biochemical pathways in living cells. In this case, the overall metabolic health of the cell influences the availability of nitrogen for synthesis of new biomolecules by using a central carbohydrate metabolite to deliver nitrogen for biosynthesis rather than a simple nitrogen molecule such as ammonia (NH3). However, cells pay a price for the homeostasis provided by such a nitrogen carrier system. Biosynthetic pathways requiring nitrogen use “complex” enzymes known as glutamine amidotransferases (GATs) to remove nitrogen from the carrier molecule glutamine. Our work has elucidated the structural basis for catalysis and control in GATs, and has uncovered several underlying features of the relevant protein structural families.

We established three-dimensional structures for the two major families among the fifteen different GAT enzymes, represented by glutamine PRPP amidotransferase (GPAT) and of guanosine monophosphate synthetase (GMPS). This work showed that the GPAT and GMPS enzymes each have a structural domain for removal of nitrogen from glutamine and another for addition of nitrogen to their respective acceptor substrates.

A fundamental question from the initial structural work was how the dual catalytic domains work together to transfer nitrogen from glutamine in one active site to the acceptor substrate in the other. We showed that during each catalytic cycle a narrow tunnel for transfer of ammonia forms transiently between the two active sites of GPAT. Furthermore, the structural change that forms the tunnel is also a molecular signal between the distant active sites, allowing precise coupling of the catalytic activities. These results led to hypotheses that all GAT enzymes produce simple ammonia in one catalytic domain and channel it to a second catalytic domain, and that complex enzymes are assembled from separately evolved catalytic modules. These ideas have been verified for other GAT enzymes, most recently by ourselves for imidazole glycerol phosphate synthase (IGPS).

One of the most important and fascinating aspects of structural biology is the discovery of unanticipated connections between biological systems, and the predictive power this confers. Following the initial GPAT structural work, we discovered, in collaboration with other structural biologists, that the GAT domain of GPAT is a member of an enzyme superfamily that catalyzes a variety of hydrolytic reactions. Members of the superfamily are so far diverged from their common ancestor that their homology was not detectable by analysis of amino acid sequences, but only by comparison of three-dimensional structures and by their similar chemistries. Characterization of structural superfamilies is important to assignment of functions to proteins first identified in genome sequences.

The theme of protein families is present throughout our work. For example, the second domain of GPAT is a member of a protein family whose members bind PRPP. We have used the structures of GPAT and other family members to develop a structure-based catalytic mechanism for the entire family. These proteins were all thought to be enzymes catalyzing various additions to the acceptor substrate PRPP. However, Nature has adapted some members of the family to regulatory function. We solved crystal structures of two of the regulatory proteins, and have used our understanding of the molecular mechanisms of the family to explain their regulatory properties.

Another system we have studied is the photosynthetic energy-transducing cytochrome b6f complex. Photosynthesis is the remarkable conversion of light energy to chemical energy. Light is transduced to electrochemical energy by splitting water into protons, electrons and molecular oxygen, and by separating charges across a lipid membrane. Chloroplasts accumulate an electrochemical potential by passing protons and electrons through several proteins in the photosynthetic membrane. We study cytochrome b6f, which transfers electrons between the two light-absorbing protein complexes of photosynthesis and, in the process, contributes to the transmembrane proton gradient that is the basis of the electrochemical potential. We discovered a buried water chain inside cytochrome f and showed that it is highly conserved throughout the biological range of the cytochrome. The water chain may assist in the poorly understood process of proton translocation. We used the structures of cytochrome f and the Rieske protein to build a picture of the intact b6f complex and compared this with the analogous respiratory complex. The parallel systems for energy transduction in photosynthesis and respiration are an excellent example of the combination of conservation and diversity in complex biomolecular systems. Our work has led to an understanding of which energy-transducing steps of photosynthesis are homologous to those of respiration and which differ.

Abstract

Catalysis, Channeling and Signaling in Complex Enzymes
Living organisms are supported by an enormous number of biochemical pathways. Sophisticated, and sometimes very subtle, control systems regulate these biochemical pathways according to the needs of the cell at any time or place. One example of subtle control is the system for delivery of nitrogen to biochemical pathways that synthesize nitrogen-containing molecules. A carrier system for nitrogen is linked to the central pathway that “burns” carbohydrates to produce energy so that the availability of nitrogen for synthesis of new biomolecules is influenced by the cellular metabolic state. In exchange for this sophisticated control feature, biosynthetic pathways requiring nitrogen must abstract it from the carrier molecule glutamine. Accordingly, Nature has evolved a set of “complex” biological catalysts known as glutamine amidotransferases (GATs). The structural basis for catalysis and control of GATs has been elucidated from crystal structures of three GAT enzymes, which have the dual function of abstracting nitrogen from glutamine and adding it to a variety of acceptor-substrate molecules.

Among the fifteen different GAT enzymes, at least two different protein families transfer glutamine nitrogen to acceptor substrates. Crystal structures of glutamine PRPP amidotransferase (GPAT) and of GMP synthetase (GMPS), which represent the two major GAT families, established that each of the enzymes has two structural domains with widely separated active sites. The initial structural work on GPAT and GMPS also uncovered the detailed structures of the active sites that catalyze removal of nitrogen from glutamine, which are quite different in these enzymes.

However, the initial structures did not explain how the dual catalytic domains work together in each enzyme. A subsequent crystal structure of GPAT, trapped in the form most relevant to catalysis, showed that the enzyme forms a narrow tunnel between the two active sites. The tunnel is created when a floppy protein loop closes over the PRPP acceptor substrate. This established that the glutamine active site is chemically distinct and produces ammonia, which is transferred through the tunnel to the second active site. Based on ideas from the closed-loop structure, it was shown that the closed floppy protein loop also signals the glutamine active site to begin producing ammonia.

GPAT is a prototype for other GAT enzymes, all of which appear to have ammonia tunnels between separated active sites. The complex enzymes are thus assembled from simpler, separately evolved catalytic modules. The newest GAT enzyme structure, of imidazole glycerol phosphate synthase (IGPS), is unlike GPAT. IGPS has a permanent ammonia tunnel between the two active sites. The tunnel carries ammonia through the core of the protein, but is blocked by a “gate” in the resting enzyme. We anticipate that the gate will open at the appropriate moment in the catalytic cycle.

Biography

Professor Nicholas A. Peppas, Showalter Distinguished Professor of Biomedical Engineering, was presented the prestigious Herbert Newby McCoy Award during the University Honors Convocation held April 14, 2000, for contributions to science for his research on therapeutic formulations for protein and drug delivery.

Professor Nicholas A. Peppas is the Showalter Distinguished Professor of Chemical and Biomedical Engineering of Purdue University. He has been at Purdue since 1976 and holds joint appointments in the School of Chemical Engineering and the new Department of Biomedical Engineering, which he helped found. In addition, he is the Director of the National Science Foundation Program on Therapeutic and Diagnostic Devices, an innovative educational, training and research program formed wit h the support of NSF in 1999 and spanning seven different schools and departments in the Lafayette and Indianapolis campus.

Peppas was educated in chemical engineering at the National Technical University of Athens, Greece (Dipl.Eng., 1971) and at the Massachusetts Institute of Technology (Sc.D., 1973). In addition to his Purdue appointment, he has served as a Visiting Professor at the Universities of Geneva (Switzerland), Paris XIII (France), Parma (Italy), Naples (Italy), Pavia (Italy), Hoshi (Tokyo, Japan), Hebrew (Jerusalem, Israel) and the California Institute of Technology. In 2001, he will be a Visiting Professor at the Free University of Berlin (Germany), and at the University of Santiago de Compostela and the Complutense University of Madrid (Spain).

His research contributions cover a wide range of fundamental studies in macromolecular science, drug delivery, biomedical polymers, mass transfer, polymerization kinetics and biomedical engineering. His group has contributed to the dynamics of macromolecular chains in dilute and semi-dilute solutions, as well as to the behavior of complex macromolecular chains in contact with biological surfaces. He is internationally known for his work on the preparation, characterization and evaluation of the behavior of a class of crosslinked polymers known as hydrogels, which have been used as biocompatible materials and as carriers in controlled delivery of drugs, peptides and proteins

Peppas’ work does not only address the fundamentals of his field but has also found a wide range of applications in the biomedical field. His group pioneered the use of hydrogels in drug delivery applications, including epidermal bioadhesive systems and systems for the release of theophylline, proxyphylline, diltiazem, and oxprenolol. Upon study of the critical behavior of intelligent polymers, Peppas and his group were the first to employ such pH-sensitive and temperature-sensitive systems for modulated release of streptokinase and other fibrinolytic enzymes. His group has also developed novel transmucosal controlled release devices. More recently, his group has announced new inventions of oral insulin delivery systems and new biomaterials. Peppas’ group has also invented new materials for hard, oxygen-permeable contact lenses, and for reconstruction of vocal cords.

In recognition of his research accomplishments he has received honorary doctorates from the University of Ghent (Belgium, 1999), the University of Parma (Italy, 1999), and the University of Athens (Greece, 2000).

Peppas is the co-author or coeditor of 25 books and volumes, and the author of 650 publications, 280 proceedings papers and preprints, 200 abstracts and 10 patents. He is one of the most cited scientists in the world according to the recent ISI survey of most cited authors for the period 1981- June 1997. Since 1982, he has been the editor of the premier Journal in his field, Biomaterials. Since 1998 he has been one of the editors of Advances in Chemical Engineering.

Peppas has been recognized by more than 60 awards including the 2000 General Electric Senior Research Award of ASEE recognizing the best engineering researcher of the USA,; the 1999 Research Achievement Award in Pharmaceutical Technology of the American Association of Pharmaceutical Scientists,; the 1995 APV-International Pharmaceutical Technology Medal,; the 1994 Food, Pharmaceutical and Bioengineering Award of the American Institute of Chemical Engineers,; the 1992 Clemson Award for Basic Research of the Society for Biomaterials,; the 1992 George Westinghouse Award of ASEE,; the 1991 Founders Award for Outstanding Research from the Controlled Release Society,; the 1988 Curtis McGraw Award of ASEE for best engineering research under the age of 40,; and the 1984 Materials Engineering and Sciences Award of the American Institute of Chemical Engineers.

Peppas has been elected a Founding Fellow of the American Institute of Medical and Biological Engineering (1993), a Fellow of the American Association of the Advancement of Science (2000), a Fellow of the American Physical Society (1997), a Fellow of the American Institute of Chemical Engineers (1997), a Fellow of the Society for Biomaterials (1994), a Fellow of the American Association of Pharmaceutical Scientists (1993) and an Honorary Member of the Italian Society of Medicine and Natural Sciences (1996). In 1991 he was named a Polymer Pioneer by Polymer News. He has supervised the theses of 45 Ph.D. students, including 20 current professors in other Universities, and another 70 students, postdoctoral fellows and visiting scientists.

Abstract

Novel complexation copolymer networks of poly(methacrylic acid) grafted with poly(ethylene glycol) have been shown to be excellent carriers for proteins due to their pH-sensitive swelling behavior as a result of the formation of reversible interpolymer complexes stabilized by hydrogen bonding between the carboxylic acid protons and the etheric groups on the grafted chains. Additionally, the presence of the PEG grafts stabilizes entrapped peptides and proteins. Because of the complexation phenomena in these networks, the characteristic mesh size in these gels is an order of magnitude greater in the uncomplexed state than in the complexed state. Because of their oscillatory swelling behavior, these gels can be used as oral carriers for insulin and calcitonin where the release of the bioactive agent in the intestine is preferable. Upon oral administration of insulin loaded gels, the blood glucose levels in rats were significantly reduced due to release of insulin in the upper small intestine. Recent studies with nanoparticles of these gels in contact with CaCo-2 cells indicate lack of cytotoxicity and improved permeability by paracellular transport.

Micropatterning and molecular imprinting using such intelligent biopolymers are powerful techniques for the preparation of films with highly specific molecular recognition capabilities. The importance of these techniques is related to the characteristics of molecular recognition. Recognition is provided by various groups that govern the specificity and affinity of biological molecules for other compounds. Molecularly imprinted polymers (MIP’s) have the same type of recognition as spatially distinct functional groups, i.e. synthetic counterparts to biological molecules. MIP’s possess “cavities” with high specificity and binding affinity for the template molecule, recognized by non-covalent, covalent or metal coordination interactions. A high amount of cross-linking provides the required rigidity of the structure. We have developed several approaches for the preparation of MIPs. Most of our studies have been with the non-covalent approach, where the interaction between monomers and template is achieved by various non-covalent interactions such as hydrogen bonding, ionic or electrostatic interactions. The clear advantage of this technique is the ease of preparation of the polymers. The monomers and template are simply mixed together and allowed to interact based on the idea of “self-assembly”. The disadvantages of this approach include the equilibrium-governed nature of the interactions and the possibility of the creation of unfavorable binding sites.

The idea of patterning the properties and surfaces at the molecular level is of extreme interest for controlling the adsorption of proteins and the attachment of cells for applications in biosensors and tissue engineering. Micropatterns aid the adsorption process tremendously by allowing for very selective adhesion.

Research Accomplishments

Peppas joined Purdue in 1976 and established an internationally recognized program in polymers, biomaterials and drug delivery. His contributions have been in polymers, biomedical engineering, biomaterials, drug delivery, mass transfer, kinetics and reaction engineering.

His polymer research has examined fundamental aspects of the thermodynamics of polymer networks in contact with solvents, the conformational changes of networks under load or in the presence of a solvent, the anomalous transport of liquids in glassy polymers, and the kinetics of fast UV-polymerization reactions. This work easily explains most aspects of gaseous diffusion.

In the field of polymer science, Peppas investigated the effects of polymer structural characteristics on the diffusion coefficient and diffusion behavior of small and large molecules, concentrating on the diffusion of liquid penetrants and macromolecules through glassy and rubbery polymers in the presence or absence of macromolecular relaxations. He developed exact molecular and approximate phenomenological theories for describing such systems. He developed new molecular theories that account for the effect of the macromolecular structure of polymers on its solute diffusion coefficient. For example, Peppas introduced two theories that can predict the dependence on the number average molecular weight between crosslinks, the hydrodynamic radius of the solute, and the degree of swelling for highly and moderately swollen nonporous membranes. Along with Prof. Caruthers, he developed necessary and sufficient conditions for Fickian and non-Fickian diffusion of a solute through glassy swellable polymers. Their continuum thermodynamic theory to describe anomalous transport in glassy polymers is a classic paper in the literature, and the experimental verification of this model has led to its wide applicability in the field.

In addition, Peppas has investigated polymer-polymer interdiffusion and provided important physical interpretation of adhesion and healing phenomena. This work has yielded models and experimental studies of systems important in controlled-release applications. He investigated gaseous diffusion through rubbery and semicrystalline polymers and through glassy polymers where gaseous solubility in the polymer is progressively altered by changing the structure of the glassy copolymer. His fundamental studies illuminated the nature of hydrogen bonding in complexation hydrogels, crystallization of polymers, rubber elasticity of networks, structure of crosslinked polystyrene, structure of polymerldiluent systems, and block copolymers. He performed significant work on the polymerization kinetics of acrylates and methacrylates, especially multifunctional monomers used in producing networks. Peppas has studied the preparation and properties of highly crosslinked polymers, which can be used in such high-tech applications as coatings, films, optical fibers, compact disks, and lenses. He developed fundamental descriptions for the propagation and termination rate constants of multifunctional polymerization/crosslinking reactions.

Peppas’ research accomplishments in bioengineering include investigation of the surface properties of hydrogels in relation to medical applications and applied such systems to the development of materials for articular cartilage, vocal cords, contact lenses, artificial kidney membranes, and artificial organs in general. Peppas performed pioneering work in developing biomedical surfaces for a portable artificial kidney and for systems to treat thrombotic effects defects through the use of streptokinase form from fibrinolytic enzymeimmobilized microparticles. He showed that diffusional effects play an important role in protein adsorption on polymeric surfaces for biomedical applications. He developed, with his research group, new biomaterials based on methacrylates, acrylates, polyvinyl alcohol) and polyethylene glycol). The research group has shown that the pH-sensitivity of many of these systems can be used to develop intelligent biomedical devices and biosensors. Finally, he contributed to our understanding of biomedical transport and interfacial phenomena, from the study of arteriosclerosis to solute transport in mucus and transport in bioadhesion.

Peppas is also a leading authority on therapeutic formulations for protein and drug delivery. He is internationally known for his work on preparing, characterizing, and evaluating the behavior of compatible, crosslinked polymers known as hydrogels, which have been used as biocompatible materials and in controlled release devices, especially in controlled delivery of drugs, peptides, and proteins, development of novel biomaterials, biomedical transport phenomena, and biointerfacial problems. In drug delivery, Peppas originated and is the leading proponent of the use of hydrophilic polymers and hydrogels for the controlled delivery of drugs, peptides, and proteins. He developed the new class of “swelling-controlled release systems,” which exhibit an unexpected time-dependent (zero-order) release due to coupling of diffusional and relaxational mechanisms. Peppas and his students were the first to propose and solve complex transport equations incorporating the viscoelastic behavior of the polymer and its relaxational behavior during swelling and drug release. He also introduced two dimensionless numbers, the Swelling Interface number (Sw) and the Swelling Area number (Sa), used by researchers in the discipline. He proposed the now well-known exponential time dependence of the quantity of drug released, which has become a most desirable equation for the analysis of non-Fickian drug delivery.

Peppas also developed and tested, with his students, systems for release of vasodilators such as theophylline and proxyphilline, beta-Mockers blockers such as oxprenolol and anti-inflammatory agents such as metronidasole. He has made seminal contributions to the understanding of release from pH-sensitive and temperature-sensitive swelling systems. In collaboration with colleagues he described the characteristics of pH-sensitive delivery, analyzed the oscillatory behavior using Bolzman superposition analysis, showed the influence of ionic strength and buffer composition on controlled release, and developed new delivery systems. Of particular interest is the work on insulin delivery using pH- and temperature-sensitive release systems. He and his research group made exceptional contributions to the development of novel mucoadhesive systems for targeted delivery.

Biography

Professor Ray A. Bressan, professor of horticulture, was presented the prestigious award during this year’s ceremony held April 16, 1999, for his significant discoveries and contributions in the field of plant biology.

Dr. Bressan is a faculty member in Purdue’s Department of Horticulture and Landscape Architecture. His outstanding research program in plant biology has led to the following important discoveries and noteworthy contributions:

• The identification and characterization of a new class of genes, the osmotins, which are involved in plant tolerance to environmental and biological stresses.
• The transformation of potato with an anti-fungal gene and the demonstration of resulting enhanced disease resistance in this major crop as well as its potential use in other crops.
• The development of the first successful genetic transformation system for sorghum, opening the potential for modification of this important world crop through genetic engineering technology.
• The discovery of a novel mechanism of protein-induced cell death in fungi and the resulting application of this to the broad area of genetic engineering for disease resistance in crop species.

Dr. Bressan received his BS in Biology in 1972 from Illinois State University and his Ph.D. in 1975 from Colorado State University. Upon receiving his Ph.D. Dr. Bressan held a postdoctoral research fellowship appointment at the MSU/DOE Plant Research Laboratory at Michigan State University. He joined Purdue in 1978 as an assistant professor of plant physiology, being promoted to associate and full professor in 1982 and 1987 respectively.

Prof. Bressan has received over $10 million in extramural funding for support of his research. He is recognized internationally for his research program in the area of plant stress physiology. He has joined numerous collaborators at Purdue and other universities across the world to establish a research program focusing on this important area of plant science.

Prof. Bressan has published over 110 papers and presented over 100 invited lectures. He has trained 14 Ph.D. students, supervised 34 postdoctoral fellows, and has hosted 32 visiting scientists. He has taught and guest lectured to numerous regular classes, and specialized graduate level classes in the areas of plant stress physiology, somatic cell genetics, and plant gene expression.

Prof. Bressan belongs to a number of societies. His primary interest, however, is with the American Society for Plant Physiologists. He serves on the editorial boards of Plant Physiology and In Vitro, Plant Section. He has held appointments on the USDA competitive grants panel for environmental stress. He frequently reviews manuscripts for Plant Molecular Biology, PNAS, Plant Cell Reports, Plant Cell and Environment, Physiologia Plantarum, Plant Cell, Plant Journal, Crop Science, Science, Plant Physiology, and the Journal ASHS. Every year he also reviews several competitive grant proposals submitted to NSF, DOE, and USDA panels.

Prof. Bressan’s research program extends into many departmental laboratories here at Purdue and other universities across the nation and the world. He brings people together in productive collaborative efforts. He significantly contributes to the professional development and vision of the collaborative mode of research.

Abstract

Plants produce a plethora of toxic proteins, and many have been shown to act in defense against predatory or pathogenic organisms that they encounter . Although the induction of defense protein accumulation by plants has been extensively studied, the mechanisms by which these toxins act to protect against invasive organisms is poorly understood. The common bakers yeast Saccharomyces cerevisiae has been used extensively as a molecular and genetic model organism. It has also proven invaluable in our studies on the mechanism of action of plant defensive proteins. Using yeast as a model we have demonstrated that the plant antifungal protein osmotin is dependent on the function of several genes which control important properties of the fungal cell wall including the pir genes and genes encoding components of an osmotin-induced signal pathway. Osmotin toxicity is also dependent on mnn4, mnn6 and mnn2, genes which are required for the transfer of mannosylphosphate to cell wall mannans. The mnn2 gene encodes an a -1,2-mannosyltransferase catalyzing the addition of the first mannose to the branches on the poly-l,6-mannose backbone of the outer chain of cell wall N-linked mannans. Null mnn4, mnn6 or mnn2 mutants are defective in alcian blue binding and osmotin binding. Antimannoprotein antibodies or alcian blue protect cells against osmotin cytotoxicity. The mnn1 gene encodes an a -1,3-mannosyltransferase that adds the terminal mannose to the outer chain branches of N-linked mannan. Null mnn1 mutants exhibit enhanced alcian blue binding, osmotin binding and osmotin sensitivity. Several cell wall mannoproteins bind immobilized osmotin or alcian blue. Thus mannosylphosphate residues on yeast cell wall mannans are inferred to function as osmotin receptors that facilitate its cytotoxicity. In addition, overexpression of the Oss1 gene caused super-sensitivity to osmotin. This gene encodes a seven transmembrane receptor-like protein. The OSS1 protein specifically binds to active but not to inactive isoforms of osmotin, and may thus represent the plasmamembrane receptor for these toxins. Intoxication by osmotin leads to a series of progressive cytological changes in target cells that indicates it is an inducer of program cell death. This induction occurs via a signal pathway independent of the main mitochondrial mediated pathway known in yeast.

Research Accomplishments

Dr. Bressan joined the Purdue faculty in 1978 and immediately set out to establish a vital research program in the area of osmotic stress responses in plants. Using plant cell cultures, Dr. Bressan established that osmotic adaptation was a cellular developmental process generally inherent in virtually all plant species and not a special characteristic of halophytes or xerophytes as previously thought. His work in this area laid the foundation for establishing the importance of several metabolic processes that could (and would) eventually be manipulated by genetic engineering to affect osmotic tolerance. His group was among the first to identify proteins that accumulate in cells in response to osmotic stress or following adaptation to osmotic stress. They designated one class of these proteins as osmotins, and have gone on in recent years to establish the intricate relationship of the osmotins to both abiotic and biotic stress. Ray’s group carefully characterized the regulation of the osmotin gene providing the first evidence for the synergistic activity of two plant hormones in regulating gene transcription (Xu et al. 1994, Plant Cell). To date, osmotin remains one of the most well characterized stress-induced genes with detailed information on the cis-elements and trans-acting factors involved in it’s transcriptional regulation.

Work in Ray’s lab took a major turn in recent years with the discovery that osmotin could protect plants from fungal pathogens (Liu et al. 1994, PNAS). In this pioneering paper, they described the development of disease resistance in potato plants overexpressing the osmotin gene. This result has led a number of other investigators to exploit the anti-fungal activity of osmotin in developing disease resistant crop plants. Since the initial demonstration by Woloshuk et al. (1991, Plant Cell), that osmotin could inhibit fungi in vitro, Dr. Bressan has pioneered a very active field of investigation into the mechanism of action of antifungal proteins. Ray’s group knew that osmotin, and other anti-fungal proteins, exhibited clear specificity, indicating that there must be cellular determinants of sensitivity and resistance in fungal cells. This led Dr. Bressan to exploit the genetics of yeast in an effort to identify targets on the cell wall or plasma membrane that interact with osmotin. Initially, they identified genetic variants of yeast with increased sensitivity to osmotin. Subsequently, Dr. Bressan’s group identified a member of a gene family from yeast encoding a stress protein localized to the cell wall. When this gene was overexpressed in yeast, the transgenic cells exhibited increased resistance to osmotin (Yun et al. 1997, PNAS). This result clearly showed that proteins localized to the cell wall are determinants of resistance to osmotin. Current evidence from Bressan’s laboratory indicates that osmotin interacts with cell wall proteins and a membrane receptor to initiate a signaling cascade culminating in fungal cell death. This work was published in the prestigious journal Molecular Cell.

Dr. Bressan has been extremely active in collaborating with several colleagues at Purdue on his research. His work on osmotic and other stress at Purdue involves collaborations with Professors Hasegawa, Handa, Rhodes, Carpita, Csonka, Gelvin and Murdock. Dr. Bressan has a long standing collaboration with Mike Hasegawa that serves as an excellent example of “team” science. Together, they have explored issues related to osmotic stress and tolerance for over 20 years. Recently, these scientists established that activation of a stress signaling cascade in plants can result in adaptations that mediate salt tolerance (Pardo et al., 1998). Research with Csonka resulted in the identification of the first polycistronic locus in tomato (Garcia-Rios et al., 1997) and with Murdock the determination that carbohydrate binding mediates the insectidal activity of the plant defense lectin GSII (Zhu-Salzman et al., 1998). As part of a McKnight Foundation funded project, Dr. Bressan collaborated with professors Hasegawa, Butler and Axtell to develop the first successful genetic transformation system for sorghum (Casas et al. 1993, PNAS). This development is not only of great importance to commercial seed companies in the U.S., but holds immeasurable promise for the genetic improvement of sorghum for many third-world countries that depend heavily on sorghum for a staple food source. Dr. Bressan is now focusing on the introduction of several important genes into sorghum including the osmotin gene. In recent years, Ray has been an active collaborator of Dr. Greg Martin in an effort to understand the role of Pto in disease resistance in tomato (Zhou et al. 1995, Cell).

In 1998, Dr. Bressan, together with his colleague, Professor Hasegawa, joined with scientists from the University of Arizona and Oklahoma State University to prepare a plant stress genomics proposal that was funded by Plant Genome division of the National Science Foundation for $8.5 million. Research on this project will focus on the identification of all of the plant genes involved in salt tolerance.

Biography

Professor Chemistry
2010 Nobel Laureate in Chemistry

Ei-ichi Negishi grew up in Japan and graduated in 1958 from the University of Tokyo. He first worked as a research chemist at the Japanese chemical fiber producer, Teijin, Ltd. From 1960 to 1963, while a Fulbright scholar, Negishi earned a Ph.D. in organic chemistry from the University of Pennsylvania. After receiving his doctorate, Negishi resumed his post at Teijin in Japan, but returned to the United States in 1966 for post-doctoral work in organoborane chemistry at Purdue University. After holding a series of academic positions at Syracuse and Purdue, Negishi became a chemistry professor at Purdue in 1979, the position he still holds. Negishi’s research has earned him numerous awards and honors, and he has given lectures throughout the world. He has published about 280 scientific papers, several patents, and a few dozen essays.

Abstract

Organic compounds including foods, drugs, clothing, plastics, and construction materials consist mostly of carbon and hydrogen, as well as several other elements such as nitrogen, oxygen, phosphorus, sulfur, and halogens. Most of the other elements in the Periodic Table are so-called metals. Currently, 80-85 elements may be considered to be metals. In earlier days of Grignard reagents and organolithiums, polarization of carbon-metal bonds in the C–M+ sense was considered to be perhaps the most important factor. Then, chemists gradually recognized the significance of empty valence-shell orbitals as Lewis acidic or electrophilic sites that metals can readily provide. The Friedel-Crafts reaction and the hydroboration and other organoboron chemistry developed by H. C. Brown are two representative examples demonstrating the significance of empty orbitals.

With transition metals such as palladium and zirconium that are extensively used in our laboratories, metal-containing species providing simultaneously one or more empty and filled nonbonding orbitals are readily available often as long-lived species. In some fundamental sense, they are like organic singlet carbenes and nitrenes of generally short lives. With both acidic and basic sites that can serve as LUMO (lowest unoccupied molecular orbital) and HOMO (highest occupied molecular orbitals), respectively, many of the transition metal compounds are chemically very versatile, and their chemical processes dominated by low-activation energy concerted processes are generally facile, be they oxidative, reductive, or of non-redox type. This is one of the important bases for their use as catalysts, as opposed to stoichiometric reagents.

Yet another important principle that we and others have begun to fully recognize is the ubiquitous opportunity for activating electrophiles with electrophiles. Whereas the higher acidity of monomeric metal species relative to associated dimers (i.e., one is better than two), has been well recognized and extensively exploited, a seemingly contradictory principle that dimeric species are more acidic than monomers (i.e., two is better than one), has not been well recognized and widely exploited, even though it has been encountered in the Ziegler-Natta reaction and many other acid-catalyzed reactions.

This talk discusses several representative catalytic and stoichiometric reactions involving nickel, palladium, titanium, and zirconium, and illustrates the generalizations presented above.

Research Accomplishments

In 1966, Ei-ichi Negishi began devoting himself to research on organometallic chemistry when he came to Purdue as a postdoctoral associate in Professor H. C. Brown’s research group. Negishi participated in Brown’s systematic exploration of organoboron chemistry which amply demonstrated the magical power of an empty orbital.

At Syracuse University, Negishi began his career exploring organotransition metal chemistry for organic synthesis. With the recognition that various reactions of 24 d-block transition metals for the formation of carbon-carbon and other types of bonds can be classified into just a few to several fundamentally discrete patterns, i.e., (1) reductive elimination, (2) carbometallation and related addition reactions, (3) migratory insertion, and (4) nucleophilic and electrophilic attack on ligands, he initially focused his attention on reductive elimination, and developed the nickel-catalyzed cross-coupling reaction of organoaluminums. This led to the discovery of the corresponding palladium-catalyzed organoaluminum reaction in 1976. Negishi’s systematic exploration led to findings on palladium-catalyzed cross-coupling reactions of organometals containing aluminum, magnesium, zinc, and zirconium, thus establishing one of the most straightforward and versatile methods for the construction of organic compounds, before a number of his followers, notably J. K. Stille and A. Suzuki, began developing related methods involving tin, boron, and other metals.

While Negishi’s efforts regarding Pd- or Ni-catalyzed cross coupling continue, in 1978 he began publishing in his second major area of research – carbometallation of alkynes and alkenes. The following five represent his major contributions in this area:

1. Zirconium-catalyzed carboalumination of alkynes (since 1978),
2. Zirconium-catalyzed enantioselective carboalumination of alkenes (since 1995),
3. Zirconium-promoted cyclization reac- tions of alkenes and alkynes (since 1985),
4. Palladium-catalyzed cyclic cascade carbopalladation (since 1988), and
5. Palladium-catalyzed cyclic acylpalladation (since 1983).

In the Zr-catalyzed carboalumination and related reactions, a potentially general and synthetically important principle of activation of electrophiles by electrophiles through dimeric association (two is better than one) has emerged. This concept has not only promoted the discovery and development of catalytic bimetallic reactions but also helped delineate mechanisms of zirconium- and titanium-catalyzed processes. Negishi’s contributions in the area of carbometallation are easily as important as those on reductive elimination, and their widespread applications by others similar to the case of palladium-catalyzed cross coupling appear to be imrninent.

More recently, Negishi and his research group are discovering and developing novel migratory insertion reactions of organozirconium and other organometallic species other than widely known carbonylation. This is one area of research Negishi hopes to pursue over the next several years.

Biography

The recipient of the Herbert Newby McCoy Award for 1997 is Gregory B. Martin, Associate Professor of Agronomy. Professor Martin was born in East Lansing, Michigan, where he later attended Michigan State University, obtaining a B.S. in crop science and a Ph.D. in genetics at the MSU/DOE ” Plant Research Laboratory. Martin held an NSF plant biology fellowship to conduct postdoctoral research at Cornell University. He joined the Purdue agronomy department in 1992, where he teaches Introduction to Genetics, AGRY 320. Martin was awarded a David and Lucile Packard fellowship in 1995. In addition to the Packard fellowship, Professor Martin’s research is supported by the NSF, USDA, USDA-BARD, and Monsanto. His research on plant disease resistance is described in over 25 publications and he has presented more than 50 lectures at universities and various national and international meetings over the past five years.

Abstract

Diseases caused by bacteria, fungi, viruses, and nematodes cause major economic losses to crops throughout the world. Research in Professor Martin’s laboratory focuses on understanding the molecular basis of pathogen recognition and subsequent signal transduction events that are involved in plant disease resistance. The work focuses on resistance to bacterial speck disease in tomato that is governed by a “gene-for-gene” interaction in which the Pto resistance gene in the plant recognizes the expression of the avrPto avirulence gene in the pathogen. Pto encodes a protein kinase and avrPto encodes a small hydrophilic protein. Martin’s research team investigated the role of Pto and AvrPto in plant-pathogen recognition and found that the two proteins physically interact in the plant cell. The team currently is determining the recognition specificity domains of both AvrPto and Pto and is testing specific models to understand how the physical interaction of these two proteins initiates disease resistance. To understand the role of the Pto kinase in signal transduction, researchers in Professor Martin’s laboratory isolated genes from tomato that encode Pto-interacting (Pti) proteins. Pti proteins include a protein kinase (Pti1) and a class of DNA-binding proteins (Pti4/5/6). Martin will discuss these data and present a model for the molecular basis of Pto- mediated disease resistance.

Research Accomplishments

Professor Martin’s work focuses on understanding the molecular basis of disease resistance in plants, Most of his work has been with tomato bacterial speck disease, which is caused by the organism Pseudomoeas syringae pv. tomato. Resistance to bacterial speck is typical of many “gene-for-gene” interactions, in which a single resistance (R) gene in the plant responds to the expression of a single “avirulence” (avr) gene in the pathogen. In the case of bacterial speck disease, the Pto resistance gene in tomato responds to the expression of the avrPto gene in the bacterium. Disease susceptibility results if either Pto or avrPto is absent in the corresponding organisms. Martin applied a new gene isolation strategy termed “map-based” cloning to isolate the Pto resistance gene. Pto was the first gene to be isolated from a crop plant species using map-based cloning and was the first plant disease resistance gene that participates in a gene-for-gene interaction to be molecularly characterized. Pto proved to encode a serine-threonine protein kinase that has roles in both recognition of the pathogen and in signal transduction leading to the activation of plant defense responses. Since the early 1980s, it had been proposed that the molecular basis of gene-for-gene interactions might be the physical interaction of a signal molecule produced by the pathogen and a receptor produced by the plant R gene. However, it had been unclear how such an interaction could occur in bacterial speck resistance since Pto is probably a cytoplasmic protein and there was no evidence that the AvrPto protein is secreted from the bacterial cell. Martin’s team recently showed that the bacterial AvrPto protein functions directly in plant cells and physically interacts with the Pto kinase. These observations provided the first explanation of the molecular basis of a recognition process that occurs between plants and their bacterial pathogens. To understand the steps in the Pto signaling pathway, Martin’s laboratory used the yeast two-hybrid system to identify several Pto-interacting (Pti) proteins. One of these, Ptil, encodes a protein kinase that appears to lie downstream of Pto in a pathway leading to the localized cell death termed the “hypersensitive response.” Another series of proteins, Pti4, Pti5, and Pti6, encode putative transcription factors that are implicated in the activation of a large family of “pathogenesis-related” (PR) genes. Professor Martin’s research over the past five years at Purdue permitted the development of a comprehensive model to explain the molecular basis of bacterial speck disease resistance. In this model, it is proposed that the AvrPto protein is secreted by Pseudomonas directly into plant cells where it physically interacts with the cytoplasmic kinase Pto. The physical interaction of Pto and AvrPto determines the specific recognition between plants with the Pto gene and Pseudomonas bacteria carrying avrPto. This recognition event, which also may involve the Prf protein (known to be required for Pto-mediated resistance), activates the Pto kinase. In response, the Pto kinase phosphorylates and activates diverse downstream target proteins, each of which plays a unique role in signaling the resistance response. Ultimately, disease resistance is determined by the activation of a variety of defense responses including the oxidative burst, defense gene expression, and the hypersensitive response. In the course of his research at Purdue, Gregory Martin has worked with Professors Ray Bressan, Alan Friedman, Phil Low, Sally MacKenzie, Randy Woodson, and many outstanding graduate students and postdoctoral scientists.

Biography

Professor Agronomy

Ben S. Freiser was born in Pittsburgh, Pennsylvania. He obtained his B.S. in chemistry from the University of California in 1971 and his Ph.D. from the California Institute of Technology in 1977. While at Caltech, Freiser studied the photochemistry of ions in the gas phase, and in 1976 won the Herbert Newby McCoy Award for the “most outstanding student in chemistry.” Freiser joined the Purdue chemistry department in 1976. He was head of the analytical division from 1984 to 1988. Freiser has won the Frank Martin Award for teaching excellence in chemistry and has been named one of the 10 most outstanding teachers in the School of Science six times. His research has earned him several prestigious awards, including the ACS Pure Chemistry Award, the Fresenius Award, the Akron ACS Section Award, the Baekeland Award, the Purdue Sigma Xi Award, and the Anachem Award.

Abstract

The study of transition-metal containing ions in the gas phase offers the opportunity to probe the intrinsic chemical and physical properties of these species in the absence of complicating factors such as solvation and ion-pairing effects. The chemistry of these highly electronically and coordinatively unsaturated species is not only inherently interesting, but can provide important clues as to mechanisms occurring on surfaces and in condensed phases by yielding a better understanding of key steps and potential intermediates. Furthermore, obtaining quantitative data on metal ion-ligand bond energies and studying the periodic properties of metal ions as a function of their ground and electronic state structures are important in rendering the outcome of an organometallic reaction predictable.

Developments in Professor Freiser’s group involving Fourier transform ion cyclotron resonance (FTICR) mass spectrometry have greatly enabled the study of gas-phase ion-molecule reactions in an unprecedented multistep fashion. These developments, together with the group’s introduction of laser desorption for generating metal ions, have permitted a rapid advancement in the understanding of gas-phase transition metal ion chemistry. Recent highlights from this work will be discussed, including: (1) the chemistry and structure of metallo-carbohedrenes (met-cars); (2) metal-assisted derivatizations of Buckminsterfullerene; and (3) the photochemistry of metal-containing cations.

Research Accomplishments

A major breakthrough in Professor Freiser’s research came in 1980 with the marriage of a laser ionization source to an ion cyclotron resonance (ICR) spectrometer to generate and study the gas-phase chemistry of simple metal ions. This has been and continues to be a major thrust of his work. With this technique, metal ions are generated directly by focusing a high-powered pulsed laser onto the pure metal. This method is so superior to those used previously that this finding has materially accelerated the study of metal ions in the gas phase. In fact, laser ionization is now commonly used by most workers in the field. Another milestone in Freiser’s career was his initiation of studies of a wide variety of chemical systems with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. Freiser was in the forefront in recognizing and exploiting the potential of FTICR for fundamental chemical studies, and his group has published over 160 papers utilizing the instrument. During the past five years, Freiser’s group has been active both in the development of new methodology for FTICR mass spectrometry and in the exploitation of laser desorption-FT1CR to open up exciting new areas in metal ion chemistry. A few of the many highlights are summarized here. Freiser’s group has made outstanding contributions to the “Buckyball Story.” In 1991 the group gained attention by generating and studying exohedral complexes of MC60+ (M = transition metal) and demonstrating unequivocally that these complexes exhibit different physical and chemical properties from the then-proposed endohedral C60 complexes reported by Smalley. This put to rest a five-year-old controversy over whether Smalley was really generating endohedral complexes in his supersonic source. This project now has evolved into a study of metal-assisted derivatization of fullerenes which has, thus far, been successful in uncovering several new com- pounds including a family of bis-Bucky complexes, M(C60)2+and C60(CH2)2,3 involving 4- and 5-membered ring structures on Buckyball (dubbed Buckybaskets). These studies also reveal fundamental structural and thermochemical properties of these new materials. The study of small metal clusters has, for some time, been the focus of intense investigation. One of the driving forces for these studies is their significance in understanding the nature of the reactive sites in heterogeneous catalysis. This connection is especially clear if one considers that, to a first approximation, the surface of a bulk structure is an assembly of clusters of various sizes and isomers. Freiser and his group recently have adapted a Smalley supersonic source to the FTICR (the second such system in the world) to study metal cluster ions, Mn + (n = 2-200). The first series of papers from Freiser’s group report the most detailed product distribution and kinetic data yet obtained, yielding new structure-reactivity relationships. A new class of transition metal-carhon clusters named “metallo-carbohedrenes” or “met-cars” with the stoichiometry M8C12 has become the focus of intense investigation. The species, discovered by Castleman and coworkers, have been mainly observed as “supermagic” peaks in mass spectra obtained from supersonic metal cluster sources in which the He expansion gas is seeded with a hydrocarbon. Like the fullerenes, the metallo-carbohedrenes are of fundamental interest and also hold promise as important new materials. Investigations by Freiser’s group have provided striking experimental evidence for corroborating the theoretically most stable structure of the met-cars. Lastly, Freiser’s group pioneered the study of the photochemistry of metal-containing ions in the gas phase. In the past five years, Freiser has exploited the methodology developed in his laboratory to obtain critical metal-ligand bond energies. His group recently demonstrated the first examples of photoinduced ion-molecule reactions. This work not only yields absorption information in the near IR on ions at 10 ‘” M, but also yields fundamental mechanistic information on photocatalysis and analogous reactions in solution.

Biography

Professor Biological Sciences

Timothy S. Baker was born in Hackensack, New Jersey. He obtained a B.S. in chemistry from Duke University and a Ph.D. in biochemistry from the University of California, Los Angeles. Baker did postdoctoral research at Cambridge and Brandeis universities. He joined the Purdue biological sciences department in 1983. Baker has chaired Gordon Conferences on “Three Dimensional Electron Microscopy of Macromolecules” and has served on the editorial boards of the Journal of Ultrastructure Research and the Journal of Structural8iology. He is a member of the Advisory Committee for the National Scanning Transmission Electron Microscope Facility at Brookhaven National Laboratory. Baker’s research on structural studies of biological macromolecules is described in more than 125 publications.

Abstract

Viruses are among the most widely known and studied pathogens. They infect virtually every living organism, including bacteria, plants, insects, and mammals. Hundreds of different viruses have been identified, and while some are deadly, many cause mild symptoms or no disease at all. Everyone knows of the AIDS virus and of other viruses such as rhino (common cold), herpes, and papilloma (warts). Hence, it is no surprise that viruses are the subject of intense biochemical, genetic, and structural investigations aimed at understanding the molecular basis of viral function.

This presentation will summarize several studies in the past decade aimed at getting close-up views of these beautiful beasts with the underlying goal of trying to better understand how viruses function. Cryo-electron microscopy (cryoEM) and image reconstruction procedures allow us to obtain highly magnified images and three-dimensional structures of spherical viruses Representative examples of recent studies will highlighted to illustrate the types of information that can be obtained with current technology. For example, an infectious virus must be able to recognize and attach to a specific host cell in spite of the body’s defensive attempt (the immune response) to block or limit infection. Recent collaborative cryoEM and x-ray crystallographic studies of human rhinoviruses have revealed details of how these viruses interact both with anti bodies and with cellular receptors.

Research Accomplishments

Professor Baker’s research involves the coordinated application of high resolution cryo-electron microscopy (cryoEM) and three-dimensional (3D) image reconstruction techniques to study virus structure and to answer questions about how viruses infect a wide range of hosts including animals, plants, fungi, and bacteria.

Recent results have been obtained with several viruses in which structural information from cryoEM has been combined with biochemical and structural information obtained in collaboration with x-ray crystallographers and molecular virologists at Purdue. These studies provide the first detailed views of molecular interactions between viruses and antibodies and cellular receptor molecules, and have provided new insights about how the immune system recognizes viruses and how viruses recognize and attach to host cells. CryoEM: Highly magnified images (30,000- 50,000X) of frozen-hydrated viruses are obtained in a transmission electron microscope (TEM). The cryoEM technique requires that a very thin sample of purified virus in a buffer solution be rapidly frozen to -160 degrees Centigrade (-256 degrees Fahrenheit) or below and transferred into the microscope where images are recorded. Because the electrons used to image the virus sample also quickly damage the sample, the images must be recorded with very few electrons. CryoEM techniques are popular since they provide an objective and direct approach to both preserve and observe the “native,” hydrated structure of biological specimens. The resulting low-dose TEM images have extremely low contrast and computer analysis and processing thus become essential. 3D Image Reconstruction: TEM images (micrographs) often include a field of view containing 100 or more virus particles. The image of a single virus particle is a 2D picture or representation of the 3D virus sample, and hence generally does not contain enough information to reconstruct the 3D structure of the virus. The micrograph is digitized to enter the image data into a computer where a battery of image processing programs are used to combine data from many virus particles in order to reconstruct the 3D structure of each type of virus studied. Virus Structure/Function: The structure of a virus (or any molecule) and the nature of its environment dictate the way the molecule functions. Knowledge of structure is therefore essential to understanding how viruses work. Most viruses are large and often quite complex biological macromolecules. The simplest viruses consist of a highly symmetric coat of 60 identical protein subunits that encapsidate the genetic information (DNA or RNA) needed for the replication of progeny viruses. Complex viruses such as HIV contain thousands of protein subunits (not all identical) and also a lipid membrane and glycoproteins (proteins with sugar groups attached). Viral Life Cycle: Though there is no norm, each virus participates in a series of well- coordinated events during its life cycle. To initiate infection, viruses must first recognize and bind to the appropriate target (host) cell. Rhino-viruses, for example, only infect cells in the upper respiratory tract. Once attached to the cell, viruses deliver their nucleic acid genome (the ‘genetic payload’) to the interior of the cell via a variety of mechanisms. The host cell is then ‘tricked’ into producing up to thousands of new viruses through steps of replication, translation, and assembly. In a lytic infection progeny viruses exit the cell and infect neighboring cells or spread (e.g. by sneezing) to a new host. Fortunately, hosts with a functioning immune defense system can overcome most infections or circumvent future infections. The first line of defense often involves recognition of and binding to viruses by antibodies.

Biography

Professor of Agronomy

The recipient of the Herbert Newby McCoy Award for 1995 is John H. Cushman, Professor of Agronomy. Professor Cushman was born in Ames, Iowa, where he later attended Iowa State University, obtaining a B.S. in mathematics and then a Ph.D. jointly in mathematics and agronomy. He joined the Purdue agronomy department in 1978, served as director of the Indiana Water Resources Research Center 1984-1988, and became professor of mathematics in 1995. Cushman was twice appointed to the Office of Health and Environmental Research Advisory Committee, a committee that oversees environmental and human health research at the Department of Energy. Professor Cushman is editor in chief of the International Journal of Stochastic Hydrology and Hydraulics. His research on the physics of fluids in porous media is described in more than 120 refereed publications and one book. Cushman has given approximately 75 lectures at national and international meetings in such diverse fields as mathematics, chemistry, physics, engineering, and agriculture.

Research Accomplishments

The focus of Professor Cushman’s research is the physics of fluids in porous media. His work is unique in that it spans time/ space scales ranging from picoseconds/angstroms to years/miles. Cushman’s research contributes significantly to problems involving (i) species separation and phase change in micropores, (ii) dispersion in media with continuously evolving heterogeneity, (iii) swelling colloidal systems, and (iv) reservoir-scale dispersion of environ- mental contaminants in natural geologic media.

Species separation and phase change in micropores: Consider a fluid contained in a pore when that pore is only a few fluid-molecular diameters wide in at least one dimension. Such fluids are of importance in condensed matter physics (model systems for the study of critical phenomena), in biology (protein folding and transport through membranes), in engineering and materials science (nanotechnologies), and in environmental science (chemical ad- sorption on soil colloids). Computational statistical mechanical experiments carried out by Cushman’s group significantly enhance our understanding of such fluids. Even a fluid as simple as a rare gas mixture displays an extremely rich and anomalous behavior when confined to a structured planar system of width on the order of a few fluid-molecular diameters. The fluid’s phase diagram is changed, its transport coefficients are radically altered from those in the fluids bulk phase, and it becomes inhomogeneous and an- isotropic. The properties of the fluid depend in a complex way on the initial structure of the liquid, the structure and commensurability of the confining walls, the wall-fluid interaction, the separation of the walls, asperities within the pore walls, and, if the pore-fluid is in equilibrium with its bulk-phase, then the pore-fluid depends strongly on the bulk-phase composition.

Dispersion in media with continuously evolving heterogeneity: If a porous medium looks inhomogeneous at every scale on which it can be viewed, then it is said to have continuously evolving heterogeneity. Many natural geologic media, and more generally fractal porous media, are of this category. By using nonequilibrium statistical mechanics, Cushman’s group was first to develop general theories of conservative chemical transport in this type of system. The theories are non-Markovian, but they reduce to their appropriate Fickian counterparts in the asymptotic limits. Interestingly, these theories can be applied to turbulent bulk-phase dispersion as well as to fluids in porous media.

Swelling colloidal systems: Swelling porous media include many natural soils, baked foodstuffs (chips, cookies, pasta, breads), many drug delivery substrates, and living organisms such as sponges. Cushman’s group provided the first correct derivations and statements of Darcy’s and Fick’s laws for such systems. The group showed that contrary to classical belief, flow in swelling systems is not driven by gradients in pressure and external fields (e.g. gravity) alone, but is also driven by changes in Helmholz free energy with volume fraction (the “interaction” potential). This result is of major significance in problems of drying that involve crust formation in soils and food polymers. The Cushman group also pro- vided rational definitions for the nonequilibrium capillary and swelling (disjoining) pressures in such systems. Nonequilibrium swelling pressure gives rise to the well-known exponential swelling law when applied at equilibrium. Prior to the efforts of Cushman’s group, the exponential law had only an empirical basis.

Reservoir-scale dispersion of environmental contaminants in natural geologic media: Large-scale heterogeneities in an aquifers hydraulic and chemical character play a fundamental role in the evolution of contaminants in the environment. The work of Cushman’s group shows that uncertainty in the parameters that characterize an aquifer give rise to spatially and temporally nonlocal constitutive laws for chemical transport. When computationally implemented, these laws often lead to different conclusions regarding groundwater contamination scenarios than those commonly employed by litigators and by the Environmental Protection Agency when enforcing environmental regulations.

Biographies

Anant K. Ramdas and Sergio Rodriguez, both professors of physics, are condensed matter physicists. Their research interests are directed toward the discovery, delineation, and understanding of solid state phenomena using optical – in particular spectroscopic – techniques. Their research has focused on the physics of semiconductors and their heterostructures. While Anant Ramdas is an experimenter who employs a wide range of spectroscopic techniques, Sergio Rodriguez is a theoretical physicist who uses quantum mechanics, symmetry principles, and other theoretical techniques to obtain insights into physical phenomena. Anant Ramdas and Sergio Rodriguez have collaborated extensively over the years on a wide range of research topics in semiconductor physics. Anant Ramdas received his undergraduate and graduate education in India, obtaining his Ph.D. in 1956 from the Raman Research Institute as a student of Professor C.V. Raman; he joined Purdue the same year. In 1977, he received the Alexander von Humboldt Senior U.S. Scientist Award. In 1994, the American Physical Society awarded him the Frank Isakson Prize and in 1993 the Indian Academy of Sciences appointed him to the Raman Professorship. Sergio Rodriguez received his undergraduate and graduate education from the University of California, Berkeley, where he obtained his Ph.D. in 1958 working with Professor Charles Kittel. He joined Purdue in 1960. In 1967 he received a John Simon Guggenheim Fellowship and in 1974 the Alexander von Humboldt Senior U.S. Scientist Award. He was awarded Fulbright Fellowships in 1978 and 1990.

Research Accomplishments

Semiconductors such as elemental silicon and germanium are prototypes of crystals grown with unprecedented perfection, whose properties can be impressively manipulated in a flexible manner by the deliberate introduction of specific impurities. They are model systems in which many fundamental issues in condensed matter physics can be addressed under well-characterized conditions: How are electronic levels modified when atoms condense to form crystals? How do the atoms of a crystal vibrate? What is the nature of an imperfection – a chemical impurity – in an otherwise perfect crystal? What is the nature of the localized and collective excitations of the atoms, magnetic ions, and electrons in such crystals? These questions have led to numerous novel physical phenomena discovered through the application of spectroscopic techniques. Theoretical formulation of the physical principles underlying these phenomena have provided deep insights into concepts unique to condensed matter. Applications in solid state electronics, infrared sensors, and optoelectronics have originated in the basic understanding of semiconductors and constitute major factors in their appeal for current research. In recent years, ultrahigh vacuum techniques have been ingeniously employed in the fabrication of submicron layers of semiconductors deposited on substrates. A juxtaposition of such layers of different semiconductors leads to semiconductor, heterostructures that possess novel properties without counterparts in their bulk form. These structures are called ‘quantum well structures’ or ‘superlattices.’ A new generation of optoelectronic applications based on such structures has transformed solid state electronics. Ramdas and Rodriguez have investigated how charge carriers are bound to chemical impurities in semiconductors. Spectroscopic studies demonstrate that the charges thus bound to Coulomb centers are solid state analogs of the hydrogen atom, amenable to rigorous theoretical analysis and precise experimental investigations. Novel effects of reduced dimensionality in quantum well structures and superlattices as reflected in their electronic and vibrational excitations have been discovered by Ramdas and Rodriguez. The introduction of magnetic ions in semiconductors results in the formation of diluted magnetic semiconductors; their experimental and theoretical investigations form a major focus of the joint research of Ramdas and Rodriguez. Novel isotope related phenomena in semiconductors discovered by Ramdas and Rodriguez in recent years form the subject of their McCoy Lecture.

Biography

The recipient of the Herbert Newby McCoy Award for 1993 is Philip S. Low, Professor of Chemistry. Professor Low grew up in West Lafayette and is the son of Philip F. Low, Professor Emeritus of Agronomy and 1980 recipient of the McCoy Award. The younger Low received his B.S. from Brigham Young University in 1971 and his Ph.D. from the University of California, San Diego, in 1975. After one year as a postdoctoral research associate at the University of Massachusetts, he joined the Purdue chemistry faculty in 1976. His research on the structure and functions of cell membranes is described in more than 120 publications from his laboratory. He is a past fellow of the International Union Against Cancer, a recipient of the Purdue Cancer Research Award, and a member of an NIH Study Section. In addition to biochemistry, his interests include sports, backpacking, and music.

Research Accomplishments

The cell membrane serves as a barrier to prevent loss of needed cellular components and to protect against entry of unwanted foreign substances. While exclusion of toxins, pathogens, genes, antibodies, exogenous enzymes, and drugs, etc., is normally essential for cell survival, the same beneAcial barrier also can prohibit administration of desired exogenous molecules that repair diseased cells or exterminate cancer cells. To circumvent this barrier, Philip S. Low and colleagues have conjugated otherwise impermeable molecules to vitamins that enter cells by receptor-mediated endocytosis. In this process, the vitamin is chemically attached to the desired therapeutic agent at a site on the vitamin that doesn’t interfere with its capture by a cell surface vitamin receptor. After the vitamin-drug conjugate diffuses to the cell, it docks with the above receptor, invaginates with the receptor and surrounding membrane to form an endosome inside the cell, traffics to the Golgi apparatus and endoplasmic reticulum, and then escapes into the cytoplasm by a process not yet fully understood. By this method, molecules of diverse chemical composition, different electrostatic charge, and varied size, with no natural ability to penetrate cell membranes, all have been success- fully delivered into vitamin receptor-bearing cells. Because specific vitamin receptors are highly enriched on certain cells, the vitamin conjugation technology also has been exploited to target attached drugs to speci6c cells in live animals and other heterogeneous cell systems. The most striking example of this selectivity involves folic acid whose receptor is found almost exclusively on cancer cells. By linking impermeable toxins to this vitamin, it has been possible to exterminate cancer cells without harming or modifying adjacent normal cells. Aside from the application to cancer therapy, uses in other areas of human medicine also have been explored or envisioned. These include:

• gene therapy for inherited disorders
• antisense DNA treatment to inhibit expression of unwanted genes
• oral or pulmonary delivery of hormones, drugs, and vaccines
• targeting of radio pharmaceuticals for imaging purposes
• delivery of therapeutic enzymes and other proteins into malfunctioning cells

Applications in basic science also are being developed for laboratory uses.

Biography

The recipient of the Herbert Newby McCoy Award for 1992 is Nicholas J. Giordano, professor of physics. Professor Giordano is a condensed matter physicist whose interests include the behavior of electrons in ultra-small structures and statistical mechanics. He was an undergraduate at Purdue and did his graduate work at Yale, where he obtained his Ph.D. in 1977. After a brief stint on the faculty at Yale, he returned to Purdue in 1979. He was an Alfred P. Sloan Foundation Fellow from 1979 to 1983 and is a Fellow of the American Physical Society. In addition to physics, his interests include running and music.

Abstract

The technology that has brought digital watches to your wrist and powerful computers into your home has been powered in large part by advances in the fabrication of small electronic circuits. Current technology routinely produces transistors and other components with sizes of a few micrometers (about one-tenth of the diameter of a human hair). This technology has been fueled in part by more advanced techniques that now are capable of producing structures nearly a factor of 1,000 smaller than those found in present-day integrated circuits. These state-of-the-art techniques are of practical interest, since they likely will form the basis for future generations of microelectronics. They are also of interest from a fundamental point of view, since they make possible the fabrication and study of physical systems whose sizes are intermediate between microscopic (i.e., atomic) and macroscopic; this regime has become known in recent years as “mesoscopic.” Experiments over the past decade have shown that these systems exhibit a variety of novel properties. 1VIany of these properties illustrate (and depend on) the quantum mechanical behavior of electrons; in this sense, the ability to assemble structures whose behavior is closely dependent on quantum mechanics makes it fair to refer to a worker in this field as a “quantum mechanic.” This talk will be a description of some of the ultra-small structures that have been studied in recent years, and will include discussion of a few of the fundamental physical phenomena that they have been used to explore. The emphasis will be on work being done at Purdue and on prospects for the future.

Research Accomplishments

Most physical phenomena possess a characteristic length scale. For example, water droplets that fall from a faucet all have the size of a few millimeters, which is determined by properties of water, such as surface tension. Likewise, many phenomena found in condensed matter have their own characteristic lengths. These length scales often are not apparent when one considers the properties of a “bulk” (i.e., large-scale) system. However, if one makes the size of the system comparable to the characteristic length scale of a particular phenomenon, then it is often the case that the phenomenon will be strongly modified, and the behavior will be very different from that found in a corresponding bulk system. For processes involving electron motion (i.e., electrical conduction), the characteristic length scales are commonly in the range of 10-1,000 nanometers (1 nm = 10-9 m). Hence, for the size of the system to have an effect on the electrical properties it requires the fabrication of systems in this size range. Nicholas Giordano has spent the past decade studying conduction processes in ultra-small metallic structures. This work has been made possible by the development of several methods for fabricating structures with one or more lateral dimensions of 10-1,000 nanometers. In his first work within this area, Giordano studied the influence of quantum mechanical interference effects on the electrical conductivity of one- dimensional metals. These effects cause the conductivity to exhibit interesting dependences on temperature and magnetic field. These effects also make the conductance extremely sensitive to the location of every impurity in the system. The motion of only a single impurity can yield a sizable change in the conductance, and Giordano’s group was the first to observe this effect in metallic structures. In more recent work, Giordano and co-workers have examined a number of other problems. Topics that have been studied include superconductivity in one dimension, the effect of microwave fields on electron coherence, and the behavior of magnetic impurities in one- and two-dimensional metals. In all of these cases, the behavior is affected greatly by making the system size comparable to the relevant characteristic length scales. This has led to new insight into these fundamental problems.

Biography

The recipient of the Herbert Newby McCoy Award for 1991 is William J. Ray, Jr., Professor of Biological Sciences. William Ray is a biochemist whose early interest was in chemical catalysis. After obtaining a Ph.D. degree in organic chemistry in 1957 at Purdue University, he did postdoctoral work at the Brookhaven National Laboratory. After two years as an assistant professor at Rockefeller University, he joined the faculty of the Biological Sciences Department at Purdue, where he won successive National Institutes of Health Career Development Awards. In 1988 he served as co-chair for the Gordon Conference on Enzymes, Coenzymes and Metabolic Pathways. Professor Ray is married and has two children and two grandsons. He spends part of his leisure time camping and in ecological management at home with his wife. He also regularly plays squash and has won the Purdue Squash Club title on several occasions.

Abstract

Life is a continual trade-off between stability and instability. Without stability there would be no lasting structure. Without instability there would be no immediate response to stimuli. The chemical instability that characterizes living systems and that drives growth, adaptation, and reproduction involves a host of chemical reactions that, from an energetic stand- point, are “downhill.” Such reactions would proceed in the absence of catalysts, but would proceed slowly and in a haphazard manner. But living systems utilize catalysts, many of which can be regulated, to facilitate arrays of downhill reactions, selected according to need. These catalysts are specialized proteins called enzymes. The reactions they facilitate involve the making and breaking of chemical bonds that convert one metabolite into another. This talk will focus on one such catalyst; what we know about its structure, how it facilitates the bond making/breaking that interconverts two specific metabolites, and how it fits into the general biochemical scheme. The enzyme is phosphoglucomutase. It is a ubiquitous enzyme, and likely is present in all living systems. It is involved with the metabolism of glucose, where it functions to interconvert glucose 1-phosphate and glucose 6-phosphate so that regulation of those enzymes involved with the subsequent degradation of glucose 6-phosphate or the storage of glucose 1-phosphate can be used to control the relative importance of immediately-usable versus stored energy. While catalysis by some enzymes is relatively nonspecific, catalysis by phosphoglucomutase is exquisitely selective and amazingly efficient. Thus, the enzyme is able to convert a molecule of glucose 1-phosphate to glucose 6-phosphate even in the presence of other sugar phosphates at a ratio of 1:50,000, without disturbing the surrounding population, and it accomplishes with 0.001 sec what would require hundreds of years in the absence of a catalyst. While most enzymes simply accelerate the normal solution process of bond breaking/making, phosphoglucomutase appears to utilize a reaction mechanism that never occurs in the absence of the enzyme. The three dimensional structure of phosphoglucomutase also is unusual. Together, these observations suggest an intriguing scenario for its evolutionary development that will be considered in this talk.

Research Accomplishments

William J. Ray studied the mechanism of the butyl lithium catalyzed rearrangement of methyldiaryl sulfones during his graduate work at Purdue. His study of enzymes began during his postdoctoral training with the development of a procedure for analyzing the results obtained during chemical modification of enzymes. His “all-or none”, which was part of that procedure, was among the first of the many stoichiometric assays that now are used to distinguish between completely active and partially active enzymes. During this time, when almost nothing was known about structure/function relationships in enzymes, Ray began working with phosphoglucomutase. Rather than specialize in the application of a single technique to the study of various enzymes to which that technique is suited, Ray’s interest has been in the application of a variety of techniques to phosphoglucomutase – techniques selected for their ability to illuminate specific aspects of its structure-function relationship. However, early on he collaborated in the first study demonstrating that the identity of the aminoacyl-RNA was the critical factor in determining where an amino acid was incorporated into the polypeptide chain of a protein. Ray’s initial studies with phosphoglucomutase defined the reaction pathway of the enzyme and were the first to define the order of substrate-metal ion binding in a metal-ion activated enzymic reaction. He then assessed the thermodynamic stability of the active-site phosphate group and was the first to obtain a nuclear magnetic resonance spectrum of such a group in an enzyme. He subsequently studied the structural change that metal ion-binding produces in the enzyme during the activation step, and obtained the first electron paramagnetic resonance spectrum of a protein containing bound Mn. His use of the electronic spectrum ofbound Ni2+ and Co2+ bound to specify the coordination geometry of a metal ion-activated enzyme also represented a first. He later employed nuclear magnetic resonance techniques to show that the bound metal ion interacts directly with the enzymic phosphate group in the resting enzyme and that the phosphate group was dianionic. Recently he showed that this phosphate-metal ion interaction is maintained in the enzyme-substrate complex, and increases markedly in the transition state. Ray also was among the first to measure the internal equilibria involving substrate/intermediate/product complexes in an enzymic system and to provide evidence that the structure of the enzyme changes during catalysis. His treatment of the quantitative relationship between the rate-limiting step in an enzymic reaction and the isotopic sensitivity of that step provided a general and definitive quantitative description of rate limitations in multi-step enzymic reactions. By taking advantage of the metal ion-binding properties of phosphoglucomutase, Ray devised the only currently available assay with sufficient sensitivity to measure the blood-plasma concentration of free Zn2+, an essential metal ion. After devising a procedure to isolate gram quantities of the enzyme, he determined its amino acid sequence, crystallized it, and studied aspects of the crystal growth process. He then began an ongoing X-ray crystallographic study of the enzyme that has produced an intermediate-resolution atomic model. Recent work has involved enzyme chemistry in the crystal phase. This has led to the development of systematic procedures that hold promise for improving the informational content of protein crystals. Another current project represents the first use of Raman spectroscopy to study chemical bonding within an enzymic phosphate group in the ground-state and in the transition state for the catalytic process. In the course of his research, Ray worked with Seymour Benzer; Jeffrey T. Bolin; Robert Callender; Mark A. Hermodson; Daniel F.. Koshland, Jr.; John L. Markley; Albert S. Mildvan; Carol B. Post; George H. Reed; Michael G. Rossmann; and William E. Truce. Because of his many significant contributions to modern enzymology, Purdue University awarded Professor Ray the Herbert Newby McCoy Award in 1991.

Biography

The recipient of the Herbert Newby McCoy Award for 1990 is R. Graham Cooks, Henry Bohn Hass Distinguished Professor of Chemistry. Graham Cooks is an analytical chemist whose research interests cover instrument development, fundamentals, and practical applications of mass spectrometers. He was born in South Africa, educated at Cambridge, and entered the United States through Kansas. He has Ph.D.s from the University of Natal and Cambridge University in organic chemistry. He taught at Kansas State University from 1968 to 1971 and since then has been at Purdue University. Apart from research, his main enthusiasms are gardening and poetry. Professor Cooks’ work has earned him the Thomas medal for contributions to international mass spectrometry and the Instrumentation Award of the Analytical Division of the American Chemical Society.

Abstract

Miniscule amounts of particular organic compounds can be detected in the Wabash River, the smoke emitted by the North Power Plant, and the soil around the Entomology Building. Methods for making these measurements are detailed in the Federal Register, and results of these analyses are the frequent subject of litigation. How- ever, even an avid listener to WBAA could be excused for being ignorant of the principal scientific instrument used to make these measurements: this instrument is the mass spectrometer. This talk will describe its remarkable evolution, from its invention by J. J. Thomson for the measurement of the mass of the electron and its contribution to the discovery of isotopes and the mass defects of atoms, to its large scale use in isotope separation during the Manhattan Project. Particular emphasis will go to chemical applications of the device which began in the 1940s with the quantitation of hydrocarbon mixtures during petroleum refining and grew to include molecular weight, molecular formula, and structural characterization of organic, inorganic, and, most recently, biological compounds. Special attention will go to current capabilities of mass spectrometry, including on-line analysis of bioreactors, biopolymer sequencing, and the ability to contain gaseous ions in miniature ion traps where their reactions can be followed and their chemical structures determined. Problems studied in collaboration with other Purdue scientists, such as cactus taxonomy, drug metabolism, chemical carcinogenesis, catalyst characterization, the chemical structure of coal, and the nature of the active principles in traditional herbal remedies will be described.

Research Accomplishments

Graham Cooks studied natural products – including the isolation and structural characterization of alkaloids from mangrove species – for his graduate work. He spent two years on the project before a two-day stint on a mass spectrometer yielded the correct answer. Not quite convinced, he studied organic mechanisms at Cambridge, but simultaneously began a second, largely nocturnal career, examining reactions in the mass spectrometer. Over the past 10 years his group has built eight new mass spectrometers. Several of the instruments have been developed in collaboration with manufacturers and have served as prototypes of commercial instruments. There is a revolution underway in/mass spectrometry, and Cooks and his group are proud to be a part of it. Cooks pioneered the use of tandem mass spectrometers (MS/MS) for the analysis of complex mixtures, recognizing the capabilities of such instruments for rapid isolation of compounds of interest and their molecular characterization through reassembly of the fragments yielded upon collision with gas molecules. The method was developed in 1975 and is now widely used, hundreds of instruments being applied in pharmacological, environmental, and chemical laboratories world-wide. Hand in hand with this applied work, Cooks has studied fundamental aspects of ion chemistry. Of particular interest was the conversion of translational energy of a polyatomic ion into internal energy during a collision. Out of these experiments grew the technique of angle resolved mass spectrometry (ARMS) in which the scattering angle was selected as a route to selecting more or less energetic ions. Other work of fundamental interest concerned the consequences of collisions of polyatomic ions with surfaces in the 10-10,000 eV energy range. Cooks and his group have worked almost alone on this topic over the past five years, delineating the phenomena which occur. They have demonstrated its potential applicability in both surface and molecular characterization. A related topic concerns the characterization of organic compounds on surfaces. Cooks was one of the pioneers of secondary ion mass spectrometry (SIMS), a technique which allows the analysis of thermally labile, non-volatile compounds by mass spectrometry. One result of this work was the extension of mass spectrometry from organic to biological compounds. For mass spectrometry to develop into a major tool in the biological sciences it is necessary that the mass range of mass spectrometers be extended. Working with a new ion trap instrument, the Cooks group recently extended the mass range 100-fold, demonstrating the ability to record mass spectra to about 105 Dalton. The consequences of these capabilities are expect d to include biopolymer and especially peptide and modified DNA sequencing strategies which improve on present methods. Recent work in Cooks’ laboratory focused on the ion trap mass spectrometer which uses electric fields to contain about 108 ions in a small volume. The ions trapped can be selected by their mass-to-charge ratios, irradiated with laser beams to study their photochemistry, translationally excited and dissociated and then re- analyzed in an MS/MS experiment. Recently a total sample of 2 attomoles (2 x 10-18 moles) of a small peptide has been shown to be sufficient to perform molecular weight measurements. Professor Cooks has significantly contributed in making mass spectrometry one of the pre-eminent methods of chemical analysis. It is for this contribution that Purdue University awarded Professor Cooks the Herbert Newby McCoy Award in 1990.

Biography

The recipient of the Herbert Newby McCoy Award for 1989 is Thomas K. Hodges, Joseph C. Arthur Distinguished Professor of Plant Physiology. Professor Hodges received a B.S. in Agronomy from Purdue University in 1958 and a Ph.D. in plant physiology from the University of California at Davis in 1962. After receiving that degree he worked as a Research Associate in Agronomy at the University of Illinois before joining the Horticulture faculty at the University of Illinois in 1963. In 1971, Professor Hodges came to Purdue as a Professor of Botany and Plant Pathology. He served as head of the department from 1977 to 1982. He was named the Joseph C. Arthur Distinguished Professor of Plant Physiology in 1989. Professor Hodges has received many awards for his research including the Charles Albert Shull Award from the American Society of Plant Physiologists.

Abstract

Crop plants have been improved systematically through plant breeding for nearly a century, and the remarkable increases in yield have been dubbed the green revolution in agriculture. We are now in the beginning stages of a gene revolution in plant biology that will extend conventional plant breeding, and it is anticipated that these new genetic technologies will provide the required boost in food production needed to feed a growing world population. The seminar will discuss the current status of genetic engineering of plants with special emphasis on transformation and regeneration of rice, maize, and other plants from single protoplasts (cells that have had the outer cell wall removed). Progress and problems in identifying genes of importance, the methods for insertion of genes into the DNA of the host plant cell, and in regrowth of the plant following insertion of the gene into an individual protoplast will be presented.

Research Accomplishments

Professor Hodges’ research in the last five years has concentrated on three problem areas: ion transport into plant cells, regenerating whole corn plants from naked (wall-less) cells, and regenerating rice plants from single cells. The first area is concerned with a better understanding of basic processes in plant nutrition. The other two are part of the world-wide effort in biotechnology to genetically engineer plants. Professor Hodges gained prominence in the 1970’s for his landmark studies on plant plasma membranes and the biochemical apparatus responsible for moving ions across the membrane from the external environment to the cell’s interior. He was the first to develop procedures for purifying plant plasma membranes; and he showed that an enzyme, ATPase, was involved in transporting ions across the membrane. In 1982, Hodges embarked on a new line of research devoted to developing the technology necessary for transforming the genetic character of plants. He focused on the major staple crops of the world that had been recalcitrant in adapting to emerging biotechnology. Regeneration of whole, reproductive plants from single naked cells called protoplasts was the goal because protoplasts are capable of receiving new genetic information. Regeneration of the cereals (corn, rice, wheat, barley) into whole fertile plants was an important undertaking because this was the major obstacle to the genetic engineering of these plants. He built a new program in plant cell and tissue culture with initial efforts focusing on corn. The overall approach was a systematic evaluation of the conditions and procedures required for regenerating plants. At this time there had been little success in regenerating corn from even large pieces of tissue. Hodges began with large pieces of somatic (body) tissue and then proceeded to smaller tissue pieces until single cells, and then protoplasts, were being investigated. Hodges recognized that the genotype as well as the nutrient environment were critical variables in determining whether or not the cells would grow. Only a few genotypes were capable of regeneration, and this led to the discovery that when a regenerable inbred plant was crossed with a recalcitrant inbred, the resulting hybrid would regenerate whole plants from single cells. This in turn led to the discovery that only two or three genes controlled somatic embryogenesis and plant regeneration. Hodges and his colleagues report the efficient transformation of corn protoplasts with two bacterial genes, simultaneously one gene makes cells resistant to an antibiotic, the other controls synthesis of a protein that is easy to measure. Thus, it is now possible to readily produce transgenic maize callus. Because of his tremendous success with the corn regeneration project, the Rockefeller Foundation asked Hodges in 1985 to develop a project on regeneration of indica rice, another major crop in the world. As with corn, indica rice regeneration was found to be under genetic control. During 1988, Hodges’ group succeeded in regenerating indica rice plants from protoplasts. This is especially important because there is a great deal of interest in genetically engineering indica rice since the indica varieties are used in most of the developing countries of the world. Thus, with the development of the techniques for regenerating these rice cells, genetic transformation of rice plants is now possible. Throughout his career Professor Hodges has shown the ability to select important research problems and pursue them with systematic and innovative vigor. He is one of the best known and most respected plant physiologists in the country. Through his research he has made his mark not only in the advancement of basic plant physiology but now in the adaptation of plant biotechnology that will lead to improved crop plants for a hungry world. It is for his recent breakthrough in this universally respected research that Purdue University awarded Professor Hodges the Herbert Newby McCoy Award in 1989.