PRESENTATION OF SPEAKERS

David Botstein is Stanford W. Ascherman Professor and Chairman of the Department of Genetics, Stanford University School of Medicine. Botstein's research has centered on genetics, especially the use of genetic methods to understand biological functions. His earliest research focused on bacteriophage genetics, DNA replication and assembly. In the early 1970s, Botstein turned to budding yeast and devised novel genetic methods to study the functions of the actin and tubulin cytoskeletons. He began his theoretical contributions on linkage mapping of the human genome in 1980 by suggesting that restriction fragment length polymorphisms (RFLPs) could be used to produce a linkage map of the human genome and to map the genes that cause disease in humans. Recent research activities include studies of yeast genetics, genomics and cell biology including the development of the Saccharomyces Genome Database, and the development of DNA microarray technology and analysis methods, and their application to classifying and understanding human cancers. Botstein was elected to the U.S. National Academy of Sciences in 1981 and to the Institute of Medicine in 1993. He has won several awards, notably the Eli Lilly Award in Microbiology and the Genetics Society of America Medal.

Michael Brown is Paul J. Thomas Professor of Medicine and Genetics at the University of Texas Southwestern Medical Center at Dallas, and since 1985 Regental Professor at the University of Texas. Born in New York 1941, he completed his MD at the University of Pennsylvania and his recidency at Massachusetts General Hospital. That was where he met his long-term co-star/companion, Joseph L. Goldstein. They both went on to be clinical associates at the National Institute of Health and later at the University of Texas Southwestern Medical School. Through their intense collaboration, the molecular regulation of cholesterol metabolism has been revealed in meticulous detail. The discovery that human cells have low-density lipoprotein (LDL) receptors which extract cholesterol from the blood stream, and that these receptors are efficient in the important human disease familial hypercholesterolemia has been of paramount importance in the treatment and prevention of coronary heart disease, the major cause of premature death in the western world. They have recently revealed new intricate mechanisms of regulation of lipid metabolism on the molecular level. For their discoveries, Michael S. Brown and Joseph L. Goldstein were awarded the Nobel Prize in Physiology or Medicine in1985. 

Linda Buck is Professor of Neurobiology at the Howard Hughes Medical Institute at Harvard Medical School. She studies the mechanisms underlying smell and taste perception. Buck and her colleagues discovered the olfactory receptor family, which detects odorants in the nose.  They also discovered receptors in the mouth for bitter and sweet taste compounds as well as a family of potential pheromone receptors. Buck and her coworkers found that olfactory receptors are used in a combinatorial fashion to detect, and encode the identities of, a vast number of odor chemicals.  Their experiments have also revealed how the combinatorial receptor codes are represented in different parts of the nervous system, where they are ultimately translated into diverse odor perceptions.

Mark M. Davis is currently The Burt and Marion Avery Professor of Immunology and an Investigator of the Howard Hughes Medical Institute, at Stanford University. Davis is known for his pioneering work on T cell recognition.  T cells are a major component of the body’s immune system and vital to our defenses against viruses and other pathogenic organisms.  In the 1980s he identified the first T cell receptor gene, and subsequently two others, which allow T cells to “see” foreign or abnormal entities.  He and his colleagues have made a number of important contributions regarding the gene organization, specificity determination and biochemistry of these molecules. He also helped to invent a technique - known as tetramer analysis - that quickly identifies, counts, and isolates T cells that recognize a particular antigen.  This technique is now widely used to monitor T cell responses to vaccinations, infections and cancer.  Recent work has focused on integrating the individual molecular interactions that underlie T cell recognition of ligands on other cells with an overall picture of the cell-cell dynamic that results, particularly the formation of what has been called “The Immunological Synapse”. 

Denis Duboule is Professor of Genetics at the University of Geneva, Switzerland. His expertise is in molecular genetics of vertebrate development. After cloning several vertebrate Hox genes and showing that they were in genomic clusters, he reported in 1988 that vertebrates, hence most animals, had conserved the colinear relationship between gene order and morphologies. Later, he showed that the same genetic system was used in both vertebrates and insects as well as in different places within one animal during development, two observations which became paradigmatic of  the  universality of developmental processes. Since more than ten years, his laboratory studies the molecular mecanisms underlying colinearity using mammalian experimental genetics, as well as their implications in an evolutionary context. 

Riitta Hari is Professor of the Academy of Finland and Head of the Brain Research Unit (BRU) at the Low Temperature Laboratory, Helsinki University of Technology, Finland. Hari coordinates since 1994 the EU's Large-Scale Facility Neuro-BIRCH (Biomagnetic Research Center in Helsinki) in the BRU. Her group has since the early 1980s been developing magneto-encephalography (MEG) with a broad scope. Whereas her physicist collegues have designed and constructed instruments and developed sophisticated signal analysis methods, Hari has focused on studies of sensory and cognitive brain functions of healthy subjects, as well as development of clinical routines for the evaluation of neurological and neurosurgical patients. Hari is especially interested in temporal aspects of signal processing in the human brain. Hari received the Award for the Advancement of European Science in 1987 (for the development of MEG), and in 2001 the Matti Äyräpää Prize by the Finnish Medical Association Duodecim. She is a Member of Academia Europaea since 1993 and of the Finnish Academy of Sciences and Letters since 1994.

H. Robert Horvitz is Professor of Biology, a Howard Hughes Investigator and a Member of the McGovern Institute for Brain Research at MIT. After having received his PhD from Harvard in 1974 with James Watson and Walter Gilbert he spent his postdoc with Sydney Brenner and his colleagues at the MRC laboratory in Cambridge, England, where he started his work on C. elegans genetics and cell and organ development. He returned to the United States in 1978 and has since pioneered the elucidation of the genetic control of programmed cell death in C. elegans by the discovery and cloning of a number of death and engulfment genes and the characterization of the gene products and their interactions. The identification of mammalian homologs has demonstrated that this process has been evolutionarily conserved and provided critical insight regarding the regulation of apoptotic cell death in vertebrates and in human disease. Horvitz has been elected member of the U.S National Academy of Sciences and of the American Academy of Arts and Sciences. He is also a recipient of a number of scientific prizes, including the Gairdner Award and the General Motors Prize for Cancer Research.

Tony Hunter is Professor in the Molecular and Cell Biology Laboratory at the Salk Institute and an Adjunct Professor in the Department of Biology at the University of California at San Diego. Hunter is a world-leading expert in cell signaling. In 1979 he made the seminal discovery of a new class of eukaryotic protein kinases that phosphorylates tyrosine residues in proteins. This led to his discovery that the oncogene product of the Rous Sarcoma Virus directly phosphorylates cellular proteins on tyrosine residues. Based on this work it was soon realized that tyrosine phosphorylation and protein tyrosine kinases make up one of the corner stones in signal transduction in eukaryotic cells, regulating cellular fate and cellular behavior. Hunter has ever since been in the forefront of cell signaling, particularly concerning the roles of protein kinases and phosphatases. Among the more recent contributions one can mention his work on the inactivation of signaling proteins through ubiquitin-mediated proteolysis. Hunter is a Member of the US National Academy of Science, and has won several prestigious scientific prizes, including General Motors Cancer Research Foundation Mott Prize and the Keio Medical Science Prize.

Eric R. Kandel is a University Professor at Columbia and a Senior Investigator at the Howard Hughes Medical Institute. A graduate of Harvard College and New York University School of Medicine, Kandel trained in Neurobiology at the National Institutes of Health and in Psychiatry at Harvard Medical School. He joined the faculty of the College of Physician and Surgeons at Columbia University in 1974 as the founding director of the Center for Neurobiology and Behavior. Kandel's research has been concerned with the molecular mechanisms of memory storage in Aplysia and mice. Recently, he has focused on the genetic switch for converting short-term to long-term memory and on how long term memory can be restricted to be synapse-specific. Kandel is a Member of the U.S. National Academy of Sciences as well as the National Science Academies of Germany and France. He has been recognized with the Albert Lasker Award, the Wolf Prize of Israel, the National Medal of Science and the Nobel Prize in Physiology or Medicine.

Roger Kornberg is a Professor of Structural Biology at Stanford. His early work encompasses the discovery and structural organization of the nucleosome.  More recent studies have shed light on the function of the nucleosome and chromatin-remodeling complexes in gene regulation.  The development of a yeast RNA polymerase II transcription system in Kornberg's laboratory, together with parallel studies in rat and human systems, led to the definition of the complete set of RNA polymerase II general transcription factors.  In 1990, Kornberg's group reported the existence of a "Mediator" that goes between gene activator proteins and RNA polymerase II.  Kornberg subsequently isolated yeast Mediator as a 20-subunit, one million molecular weight complex, and counterparts of this complex have been shown to transmit regulatory information from enhancers to promoters in all organisms from yeast to humans. The most recent work from the Kornberg laboratory centers around the determination of the 3-D atomic structure of RNA polymerase II, both in a resting condition and as an actively transcribing complex with template DNA and product RNA.

Eric S. Lander is Professor of Biology at Massachusetts Institute of Technology, and Director of the Whitehead/MIT Center for Genome Research. His research has focused on understanding the content and structure of mammalian genomes, and applying genome-scale approaches to elucidate the basis of diseases. Lander’s research group participated in creating the first genetic, physical and sequence maps of the human and mouse genomes. He developed many of the mathematical and computational tools that were used in the planning and analysis of the human genome project. His group has extensively characterized the nature of human genetic variation; these studies launched a successful international effort to create a map of human genetic variation (SNPs). His group has discovered and characterized the underlying structure of common ancestral segments in the human population. These findings have been used to identify disease genes in isolated populations and polygenic susceptibility factors for such diseases as inflammatory bowel disease and diabetes in general populations. Lander has developed and applied genome-wide analysis of gene expression to cancers, including identifying cancer subclasses and creating predictors of patient response to therapy. 

Kim Nasmyth is currently the Director of the Research Institute of Molecular Pathology (I.M.P.) in Vienna, Austria. His work has addressed the mechanisms by which genes are turned on and off during development, how DNA replication is controlled and how chromosomes ensure their segregation during mitosis and meiosis. He demonstrated the role of transcription factors in initiating the cell cycle and showed that the initiation of DNA replication depends on destruction of a CDK inhibitor (CKI) by a ubiquitin protein ligase. He discovered that sister chromatid separation depends on the same ubiquitin protein ligase responsible for cyclin proteolysis, namely the APC, and showed that its role is to activate a cysteine protease called separase. He was the first to identify the chromosomal proteins responsible for sister chromatid cohesion and demonstrated that sister chromatid segregation at the metaphase to anaphase transition is trigged by cleavage on one of them by separase. His latest work concerns the processes by which cells ensure that sister kinetochores are pulled in opposite directions during mitosis (bi-orientation) and how this is replaced during the first meiotic division by a mechanism ensuring that maternal and paternal kinetochores are instead pulled in opposite directions.

Svante Pääbo is Director of the Max-Planck Institute for Evolutionary Anthropology in Leipzig, Germany. He is one of the founding Directors of this Institute that studies the origins and history of humans from linguistic, cognitive and genetic perspectives. Born in Stockholm, Dr. Pääbo received his PhD degree from the University of Uppsala in 1986. Following postdoctoral periods in Switzerland, the UK, and USA, he became Professor of General Biology at the University in Munich in 1990, and moved to his current position in 1997. Dr. Pääbo is interested in the patterns and processes of molecular evolution and particularly the insights that can be gained into the origin and history of humans. He has pioneered the study of ancient DNA, and continues to lead in the development of procedures for analysis of DNA from archaeological and paleontological remains. Among his achievements is the reconstruction of DNA sequences from the Neanderthal type specimen in 1997, which showed that the Neanderthals did not contribute mitochondrial DNA to contemporary humans. He and his coworkers are currently investigating the genetic differences distinguishing humans from our nearest relatives, the African apes, by means of intensive study of genome structure and function. 

Elizabeth Robertson is Professor of Molecular and Cellular Biology at Harvard University. She was one of a small group of people who pioneered the use of mouse embryonic stem (ES) cells as powerful tools for genetic analysis of complex processes in the living organism.  In the early 1980s, working with Allan Bradley in Martin Evans' laboratory at the University of Cambridge, she established methods for the isolation of pluripotent ES cells from normal mouse embryos and demonstrated their ability to reproducibly colonize the germ line of chimeric mice. This finding set the stage for subsequent work by her and others who developed techniques currently in widespread use for genome modification of the mouse. Since 1992, her research has focused on signals patterning the early mouse embryo. She has shown that a single TGFb family member, nodal, acting through a variety of novel mechanisms, establishes the body plan of the mouse embryo, and determines how the embryo becomes organized along the anterior-posterior and left-right axes.

Bert Sakmann is currently Director of the Cell Physiology Department at the Max-Planck-Institut für Medizinische Forschung in Heidelberg, Germany. He received his M.D. from the Medical Faculty at the Ludwigs-Maximilian-Universität in Munich. His research interests have focussed on structure and function of ion channels in nerve and muscle and on the mechanisms underlying developmental changes in structure and function of the neuromuscular synapse. More recently his interest is on cellular and molecular mechanisms that modify, on the short and long term, synapses in the mammalian central nervous system. He was awarded the 1991 Nobel Prize in Physiology or Medicine for his discoveries concerning single ion channels in cells, together with Erwin Neher. 

Philippe Sansonetti is Professor and Head of "Unité de Pathogénie Microbienne Moléculaire" at Institut Pasteur. His major scientific contributions concern the mechanisms for rupture, invasion and inflammatory destruction of the intestinal barrier by the Gram negative pathogen Shigella. He established that the invasive potential of Shigella was encoded by a large extrachromosomal element, and subsequently identified the major virulence factors implicated in the invasive process, particularly the operons encoding the type III secretion and its dedicated effector proteins that interact with target eucaryotic cells. He further analysed in vitro bacterial entry into epithelial cells, actin-mediated intracellular motility, adherence-junction mediated cell to cell spread and macrophage apoptosis. This in vitro cell approach was subsequently followed by the in vitro reconstitution of some compartments of the epithelial barrier as well as in vivo adaptation of animal models. These approaches in combination with studies on innate and adaptive host responses has established Shigella as a model system for understanding invasive infectious disease at the molecular and cellular level. Dr. Sansonetti is the recipient of several international awards including the Robert-Koch award in1997.

Roger Y. Tsien is an Investigator of the Howard Hughes Medical Institute and Professor in the Depts. of Pharmacology and of Chemistry & Biochemistry at the University of California, San Diego. Tsien's research has been at the interfaces between organic chemistry, cell biology, and neurobiology, starting long before such interdisciplinary efforts became fashionable. He is best known for designing and building molecules that either report or perturb signal transduction inside living cells. These molecules have enabled many laboratories including his own to gain new insights into signaling via calcium, sodium, pH, cyclic nucleotides, nitric oxide, inositol polyphosphates, membrane potential changes, active export of proteins from the nucleus, and gene transcription. The optical reporter molecules are also valuable in miniaturized high-throughput screening of candidate drugs in the pharmaceutical industry. His current research goals are to understand how the spatial and temporal dynamics of signal transduction orchestrate complex cellular responses such as gene expression and synaptic plasticity.

Harold Varmus, former Director of the National Institutes of Health, has served as the President and Chief Executive Officer of Memorial Sloan-Kettering Cancer Center in New York City since January 2000. He is a graduate of Columbia University’s College of Physicians and Surgeons. Much of Varmus’ scientific work was conducted during twenty-three years as a faculty member at the University of California, San Francisco, where he and Michael Bishop and their co-workers demonstrated the cellular origins of the oncogene of a chicken retrovirus.  This discovery led to the isolation of many cellular genes that normally control growth and development and are frequently mutated in human cancer.  For this work, Bishop and Varmus received many awards, including the 1989 Nobel Prize in Physiology or Medicine.  Varmus is also widely recognized for his studies of the replication cycles of retroviruses and hepatitis B viruses, the functions of genes implicated in cancer, and the development of mouse models for human cancer. He has been a Member of the U.S. National Academy of Sciences since 1984 and of the Institute of Medicine since 1991.

James D. Watson was Director of the Cold Spring Harbor Laboratory for more than twenty-five years, and is presently President of the Laboratory. In 1953 James D. Watson, with Francis Crick, successfully proposed the double helical structure for DNA, a feat described by Sir Peter Medawar as "the greatest achievement of science in the twentieth century."  For this work, he and Crick, together with Maurice Wilkins, were awarded the Nobel Prize in Physiology or Medicine in 1962.  While a Professor at Harvard, Watson commenced a writing career that generated the seminal text, Molecular Biology of the Gene, and the best-selling autobiographical volume, The Double Helix.  Later, while leading the Cold Spring Harbor Laboratory, he was a driving force behind setting up the Human Genome Project, a major factor in his receipt in 1993 of the Copley Medal from the Royal Society that elected him a member in 1981.  Among other honors, Watson was elected in 1962 to the National Academy of Sciences and has received the Medal of Freedom, the National Medal of Science, and the Benjamin Franklin Medal. He has received honorary degrees from many universities including the University of Cambridge (1993) and the University of Oxford (1995).