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APPENDIX A S^˘ ~ ~~= =~^ A the r =~n~ - or ~~ RUED} AEBERSOLD is a founding member of the Institute for Systems Biology in Seattle, Washington, where he leads the proteomics program of the Institute. The program is focused on developing new methods and technologies for quantitative proteomics and for applying this emerging technology to enhance our understanding of the structure, function, and control of complex biological systems. Current applications of quantitative proteomics technology at the Institute for Systems Biology are directed towards the discovery of proteins markers that differentiate cancer cells from their normal counterparts, to the investigation of the mechanisms of fundamental cellular processes by the comparative analysis of the gene and protein expression profiles in cells at different states, and to studies in the area of medical microbiology. Dr. Aebersold completed his undergraduate studies in biology at the University of Basel, Switzerland in 1979 and received a Ph.D. in cell biology at the Biocenter of the University of Basel in 1984. Holding fellowships from the Swiss National Science Foundation and EMBO he joined the California Institute of Technology as a postdoctoral fellow (1984-86) and remained at Caltech as a senior research fellow (1986-~. In 1988 he joined the University of British Columbia in Vancouver as an assistant professor in the Department of Biochemistry and Molecular Biology and as a senior investigator at the Biomedical Research Centre. In 1993, he moved to the University of Washington as an Associate Professor in Molecular Biotechnology and was promoted to full Professor in 1998. He served as the Associate Director for the Science and Technology Center for Molecular Biotechnology from 1994-2000. In 2000, he left the University of Washington and joined the Institute for Systems Biology as co-founder and full faculty member. Dr. Aebersold is a consulting editor for the journal Physiological Genomics, has been a member of the Editorial Advisory Boards of Protein Science (1992-'989, Functional Proteomics (1999- presents, Analytical Biochemistry (1991-present) Functional and Integrative Genomics (1999- present) and Electrophoresis (1989-1993J Journal of Proteome Research (2001-present) and an Associate Editor for Molecular and Cellular Proteomics (200 ~-present). CHERYL ARROWSMITH is a Senior Scientist at the Ontario Cancer Institute and Professor in the Department of Medical Biophysics at the University of Toronto. She received her B.Sc. degree in chemistry from Allegheny College and Ph.D. in chemistry from the University of Toronto. She carried out postdoctoral research at Stanford University where she applied NMR spectroscopic methods toward understanding protein structure and function. Dr. Arrowsmith's current research focuses on the use of NMR and biochemical methods for understanding the structure-function relationships of proteins. Most recently she has been involved in applying structural biology methods on a genome-wide scale and is co- founder of Integrative Proteomics Tnc., a company that integrates multiple technology platforms in protein structure and function for use in pharmaceutical discovery. MARv~N CASSMAN is the Director of the National Institute of General Medical Sciences at the National Institutes of Health. After serving as a NIH postdoctoral fellow at the University of California, Berkeley for two years and as an assistant professor at the University of California, Santa Barbara for seven years, Dr. Cassman joined the NIGMS in 1975. There, he has held several different positions, including chief of the Cellular and Molecular Basis of Disease Program and Director of the Biophysics and Physiological Sciences Program. Prior to becoming the director of NIGMS, he served as deputy director from ~ 989 to ~ 996 and acting director from ~ 993 to 1996. Dr. Cassman served on the staff of the House Subcommittee in Science, Research and Technology from 1982 to 1983. He also was a senior policy analyst at the Office of Science and Technology Policy from 1985 to 1986. Dr. Cassman received a B.A. in 1954, a B.Sc. in 1957, and a M.S. in 1959, all from the University of Chicago. He received his Ph.D. from Albert Einstein School of Medicine in 1965. A-1
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JULIO CELIS is the Scientific Director of the Institute of Cancer Biology and Danish Centre for Human Genome Research, Danish Cancer Society, Copenhagen, Denmark. Dr. Celis is also the Secretary General of Federation of European Biochemical Societies (FEBS). He is on the council of the European Molecular Biology Organization (EMBO) and President of the E-BioSci Committee of EMBO, which is creating a new database network involving seven European partners from four countries with expertise in providing access to and retrieval of information in the life sciences in digital form. BRIAN T. CHAIT is the Camille and Henry Dreyfus Professor at Rockefeller and Head of the Laboratory for Mass Spectrometry and Gaseous Ton Chemistry. He is director of the NTH-funded National Resource for the Mass Spectrometric Analysis of Biological Macromolecules. His current research focuses on investigations of new techniques for volatilizing and ionizing proteins, designing and constructing novel mass spectrometers, and developing mass spectroscopic-based methodology to assist in the solution of challenging biological problems. Dr. Chait and his colleagues are applying these tools to the solution of biological problems that involve the rapid identification of proteins, the elucidation of posttransTational modifications that regulate the function of proteins, and the definition of sites of functional interaction between biomolecules. Dr. Chait received his B. Sc. (1969) and B. Sc. (Hons) (1970) from the University of Cape Town and D.Phil. (1976) in experimental nuclear physics from Oxford University. He carried out postdoctoral research at the University of Manitoba, where together with Professor Kenneth G. Standing, he constructed the first pulsed ion bombardment time-of-flight mass spectrometer. Subsequently, Dr. Chait moved to the United States where he joined the laboratory of Professor Frank H. Field, and constructed a number of mass spectrometers designed to measure biological macromolecules. FRANCIS S. COLLINS is the Director of the National Human Genome Research Institute at the National Institutes of Health. He oversees the human genome project, a complex multidisciplinary scientific enterprise directed at mapping and sequencing the entire human DNA, and determining aspects of its function. A working draft of the human genome sequence was announced in June of 2000, an initial analysis was published in February of 2001, and the completed sequence is anticipated in the spring of 2003. From the outset, the project has run ahead of schedule and under budget, and all data has been made immediately available to the scientific community, without restrictions on access or use. Dr. Collins received a B.S. from the University of Virginia, a Ph.D. in Physical Chemistry from Yale, and an M.D. from the University of North Carolina. Following a fellowship in Human Genetics at Yale, he joined the faculty at the University of Michigan, where he remained until moving to NIH in 1993. His research led to the identification of genes responsible for cystic fibrosis, neurofibromatosis, and Huntington's disease. He is a member of the Institute of Medicine and the National Academy of Sciences. DENIS HOCHSTRASSER is the director of the Clinical Pathology Depa~l~ent of the Geneva University Hospital, and President, Clinical Medicine, University of Geneva, Switzerland (www.hcuge.ch). He is also Head of the Central Clinical Chemistry Laboratory of the Geneva University Hospital. He is full Professor both to Geneva's Department of Pathology, Medicine Faculty and to the School of Pharmacy, Sciences Faculty. He was one of the founders of the Swiss Institute for Bioinformatics (www.expasy.org) and he is a scientific founder of GeneProt Inc (www.geneprot.com). Dr. Hochstrasser obtained his M.D. at Geneva Medical School, and after a visiting year at Duke, did a two-year residency and internship at UNC Chapel Hill. Dr. Hochstrasser oversees all computing activities in Geneva's Faculty of Medicine, as well as running an internationally renowned proteomics research group. Dr. Hochstrasser is known for his pioneering developments of what is now called proteomics. Dr. Hochstrasser's innovations in the methodology of two-dimensional gel electrophoresis, and his perception of the need for integration of the methodology with electronic data processing, have contributed decisively to the technique's becoming one of the main protein separation methods used in proteomics. In his own group, Dr. Hochstrasser had the foresight more than 15 years ago to initiate work on software development for what is now called proteomics. He put together a world class group, including Dr. Ron Appel, which produced the leading A-2
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2D gel analysis software package Melanie, widely used in both academic and commercial laboratories, and the standard database Swiss 2D-PAGE. Among other major developments, he was instrumental in bringing Ron Appel and Amos Bairoch together, which led to the creation of one of the first few web sites in the world, ExPASy, and the very first to be devoted to the life sciences. Most recently he and his team have been responsible for the Molecular Scanner, a technique that promises to enhance proteomic analysis in the future. JOSHUA LABAER iS the Director of the Institute of Proteomics at Harvard Medical School. He attended the University of California at Berkeley as an undergraduate where he was awarded the University Medal. His studies continued at the University of California, San Francisco where he attended medical and graduate school and where he studied steroid regulation of DNA transcription and protein-DNA interactions with Dr. Keith Yamamoto. Dr. LaBaer completed his clinical training at the Brigham and Women's Hospital in Boston, where he specialized in internal medicine and the Dana-Farber Cancer Institute in Boston, where he studied medical oncology. He also pursued research interests at the Massachusetts General Hospital in Boston in the areas of breast cancer, mammalian cell cycle regulation and cell cycle checkpoint genes. He is currently an Attending Physician at the Dana-Farber Cancer Institute and holds an academic appointment through the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. Together with Dr. Ed Hariow, Dr. LaBaer founded the Harvard Institute of Proteomics in the spring of 1999. The mission of the Institute is to use the information arising from the genome projects to revolutionize the study of proteins and their functions by enabling scientists to produce and study proteins hundreds or thousands at a time. The Institute has started an ambitious project to build a complete genome-wide collection of full-length genes in a recombinational cloning vector. The output wall be a large repository of verified cloned genes that will allow the entire proteome to be used for any experimental needs. The recombinational cloning system allows genes to be transferred en masse into any expression vector essentially overnight. The goal of the Institute is to create the human repository first and then other appropriate mode] organisms. A fundamental principle underlying the repository is that the full-length clones in the repository, along with the technology to use them, will be broadly available without restriction to all scientists academic, governmental or commercial—and will likely become a universal research standard. In this way, scientists everywhere will be able to obtain large collections of genes that can be transferred easily into the most relevant experimental systems. Since the Institute started in the spring of 1999, it has been developing the informatics and automation to begin constructing this large repository. The Institute now has a fully functional tracking database and workstation automation with the capacity to process >400 clones per week. At present, the Institute has completed a first pass of the budding yeast genome with ~95% success and there are over 3000 clones in the human repository. The Institute is now organizing a consortium of public and private entities to fund the completion of this important resource. SCOTT PATTERSON is Vice President, Proteomics at Celera Genomics Corporation in Rockville, Maryland. He has been at Celera Genomics since November 2000 establishing an industrial-scale Proteomics facility for diagnostic marker and therapeutic target discovery and development as part of the evolution of Celera into a next-generation biopharmaceutical company. The Proteomics approach r ~ ~ rat employs advanced chromatography-mass spectrometry based analyses he pioneered for therapeutic protein drug discovery at Amgen Inc. (Thousand Oaks, California) where he was from ~ 993 . When he left Amgen Inc. he was Head of the Biochemistry and Genetics department and Proteomics Team Leader. During that time he developed methods for the identification of low-level quantities of gel-separated proteins by PSD-MALDI-MS, and complex peptide mixtures by LC-MS/MS (chromatography-based Proteomics) and has published papers on these topics including a number of review articles. The Proteomics Team at Amgen Inc. was formed in 1997. Dr. Patterson came to Arngen Inc. from Cold Spring Harbor Laboratory, New York (1991-1993) where he was a faculty member. At CSHL he supervised the 2-D Gel Laboratory Core Facility in addition to his own laboratory. His research interests included protein identification technology development and investigation of the molecular mechanisms of A-3
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apoptosis. Prior to moving to CSHL, Dr. Patterson held various positions (finally as Superv~s or) in the Australian Equine Blood Typing Research Laboratory at The University of Queensland (1980-1990) in Australia where he obtained his B.Sc, and subsequently his Ph.D. in Physiology and Pharmacology. JOHN WALKER has been engaged in structural studies of the ATP syntheses from bovine heart mitochondria and eubacteria for more than 20 years. These studies resulted in a complete sequence analysis of the complex from several species and in the atomic resolution structure of the Fat catalytic domain of the enzyme from bovine mitochondria. This structure suggested that ATP is made by a rotary mechanism and provided the means for direct demonstration of rotation. Recently, he and his colleagues have established the structure of part of the Fo motor domain, which generates rotation. He has also worked on other vital proteins in mammalian mitochondria. In the early 1990's his group established the sequences of 36 nuclear encoded subunits of complex ~ (NADH ubiquinone oxidoreductase). Recently they have taken steps towards unraveling its 3-dimensional structure. In addition, throughout the past 10 years he has collaborated with Professor Palmieri at the University of Bari in Italy to identify membrane proteins that transport a range of small molecules in and out of mitochon~ia. In 1998, Dr. Walker became the Director of the MRC's Dunn Human Nutntion Unit in Cambridge, with the aim of steering nutrition research towards the fundamental understanding of the processes involved in nutrition using molecular and genetic methods. Dr. Walker is a Fellow of the Royal Society, a Fellow of Sidney Sussex College, and an Honorary Fellow of St. Catherine's College, Oxford. Among his honors are the A. T. Clay Gold Medal (1959), the Johnson Foundation Prize by the University of Pennsylvania (1994), the CIBA Medal and Prize of the Biochemical Society (1996), the Peter Mitchell Medal of the European Bioenergetics Congress, and the Gaetano Quagliariello Prize for Research in Mitochondria by the University of Bari, Italy (1997~. In 1997, Dr. Walker was awarded the Nobel Prize in Chemistry jointly with Dr. Paul Boyer for their elucidation of the enzymatic mechanism underlying the synthesis of adenosinetriphosphate (ATP). He became a Knight Bachelor in 1999. A-4
Representative terms from entire chapter: