WEDNESDAY OCTOBER 8, 2008

    MORNING SESSION: 09:30 - 12:30
    Host-pathogen and immunity: a tripartite adventure
09:30   Chairperson: Pascale Cossart (Paris)

Philippe J. SANSONETTI


Professor and Head of the Unité de Pathogénie Microbienne Moléculaire at the Pasteur Institute of Paris, Professor of Microbiology of Infectious Diseases at the Collège de France

Professor Sansonetti received his M.D. in 1979 from the University of Paris. From 1979 to 1981, he conducted research in the Department of Enteric Infections at the Walter Reed Army Institute of Research in the United States. He is a Chevalier de la Légion d'Honneur and received the Prix d'Excellence Jacques Monod en Biologie Moléculaire, the Prix AGIR du Conseil Pasteur-Weitzmann, the Grand Prix de l'Académie de Médecine, the Louis-Jeantet Prize for Medicine, and the Robert Koch Prize and Medal. He is a member of the French Academy of Sciences and a corresponding member of the French Academy of Medicine. In 2007, he was elected to the American Academy of Arts and Sciences.

Philippe Sansonetti studies Shigella, Gram-negative bacteria that cause dysentery. His goal is to decipher the molecular and cellular bases of Shigella's rupture, invasion and inflammatory destruction of the intestinal lining. He also is analysing the mechanisms of immunity against Shigella, hoping to use his findings to develop vaccine candidates.
Philippe J. SANSONETTI
(Institut Pasteur, Paris)
Bacterial pathogens: tool box to tinker the immune system, suggestion box to understand the immune system

Beyond the generic innate immune response elicited in tissues by infecting pathogens upon host perception of their prokaryotic-specific motifs (i.e. LPS, lipoproteins, flagellin, peptidoglycan) by specific sensors (i.e. TLRs, NLRs, C-type lectins), it clearly appears that these pathogens have often evolved elegant strategies to subvert this response. Upon long co-evolution with their hosts, they have accumulated genes encoding effectors capable to hit straight at the heart of signalling cascades that are essential to elicit both innate and adaptive responses, thereby reaching a compromise that may be beneficial for both 'partners'. By collaboratively studying these regulatory mechanisms, and by letting bacteria 'educate' them through their efforts to decipher these strategies, microbiologists and immunologists can hope to unravel new paradigms and to capitalize on them to foster the development of novel control strategies.
Bacterial pathogens: tool box to tinker the immune system, suggestion box to understand the immune system
10:15   Discussion
10:25   Chairperson: Jürg Tschopp (Lausanne)

Jules A. HOFFMANN


Professor and Director at the CNRS Institute of Molecular and Cellular Biology (IBMC) at Strasbourg, President of the French Academy of Sciences

Jules Hoffmann was born in Luxembourg and moved to Strasbourg, France, in 1960 to study biology and chemistry. He received his Ph.D. in 1969 at the Department of General Biology at Strasbourg University. From 1993 to 2005, he was the Director of the IBMC at Strasbourg, an Institute of 200 persons, of which the Hoffmann Research group comprises one-third.

Dr. Hoffmann holds the position of Distinguished Class Research Director with the French National Research Agency CNRS and is a Member of the Board of Administration of this agency. He is also a Member of the German Academy of Sciences Leopoldina, of the European Molecular Biology Organization, of the Academia Europaea, of the American Academy of Arts and Sciences, and of the Russian Academy of Sciences. He is a recipient of several international awards, namely the 2003 William B. Coley Award for Distinguished Research in Basic and Tumor Immunology, the 2004 Robert Koch Prize for Immunology, and the 2007 Balzan Prize for Innate Immunity.
Jules A. HOFFMANN
(Institut de Biologie Moléculaire et Cellulaire, Strasbourg)
The antimicrobial host defence of Drosophila: a paradigm for innate immunity

The fruitfly Drosophila mounts a potent defence reaction during fungal, bacterial and viral infections. We have investigated this defence and have asked three types of questions: (1) how does Drosophila recognize the invading micro-organisms; (2) how does recognition lead to activation of intracellular signalling cascades and gene reprogramming; (3) which effector molecules are produced to oppose the micro-organisms. Our results point to a sophisticated defence mechanism which is based on several circulating, transmembrane or cytosolic receptors of microbial ligands. Bound receptors trigger several distinct signalling cascades which culminate in the activation of NF-κB family members, which in turn control the expression of hundreds of immune-response genes, some of which have potent antimicrobial activities. Stringent parallels with innate immune mechanisms of mammals point to a common ancestry of this defence and will be discussed in the presentation.
The antimicrobial host defence of Drosophila: a paradigm for innate immunity
11:10   Discussion
11:20   Break
11:35   Chairperson: Richard N. Perham (Cambridge)

Wolfgang BAUMEISTER


Director and Head of the Department of Structural Biology at the Max-Planck-Institute of Biochemistry in Martinsried

Wolfgang Baumeister studied biology, chemistry and physics at the Universities of Münster and Bonn, Germany, and he obtained his Ph.D. from the University of Düsseldorf in 1973. He spent time at the Cavendish Laboratory in Cambridge, England, and in 1978 became lecturer in biophysics in Düsseldorf. In 1983, he moved to the Max-Planck-Institute of Biochemistry in Martinsried, Germany. He is also a Honorary Professor of physics at the Technical University of Münich. Wolfgang Baumeister is the recipient of numerous prizes including the Otto Warburg Medal, the Schleiden-Medal, the Louis-Jeantet Prize for Medicine, the Stein and Moore Award, and the Harvey-Prize in Science and Technology.

Wolfgang Baumeister’s research interests are in the field of cellular protein quality control. He has discovered and characterized several novel complexes which play key roles in protein folding and degradation and he made seminal contributions to our understanding of the structure and function of the proteasome. Moreover, he has pioneered the development of cryoelectron tomography, an emerging imaging technique with unique potential for bridging the divide between molecular and cellular structural biology.
Wolfgang BAUMEISTER
(Max-Planck-Institut für Biochemie, Martinsried)
From words to literature in structural biology

With the advent of computer-controlled electron microscopes and the automation of data acquisition, it became possible to obtain molecular-resolution tomograms of structures as large as whole cells. Noninvasive three-dimensional (3-D) imaging of vitrified cells is where cryoelectron tomography promises to make unique contributions by closing the gap between the cellular and the molecular worlds. Tomograms of cells at molecular resolution are essentially 3-D images of the cell’s entire proteome, and they reveal the spatial relationships of macromolecules in the cytoplasm, the 'interactome'. To exploit the imposing amount of information contained in a cellular tomogram, pattern recognition techniques must be used that are capable of detecting and identifying molecules in tomograms with a low signal-to-noise ratio through their structural signature.
From words to literature in structural biology
12:20   Discussion
12:30   Lunch
 

 

    AFTERNOON SESSION: 13:30 - 16:30
    Cardiovascular and metabolism: when metabolic alterations meet cardiovascular disorders
13:30   Chairperson: Jean-Louis Carpentier (Geneva)

C. Ronald KAHN


Professor of Medicine at the Harvard Medical School and President of the Joslin Diabetes Center at Boston

Dr. C. Ronald Kahn received his B.S. and M.D. at the University of Louisville. After training in internal medicine at Washington University's Barnes Hospital, he went to the NIH for 11 years, where he rose to head the Section on Cellular and Molecular Physiology of the Diabetes Branch of NIDDK. In 1981, he became the Research Director of the Joslin Diabetes Center. Since 1986, he has been the Mary K. Iacocca Professor of Medicine at Harvard Medical School. In 1997, he was named Executive Vice-President and Director of Joslin. In 2000, he was named Joslin's President.

Dr. C. Ronald Kahn has received the major research awards of the American Federation of Clinical Research, ADA, JDF and IDF, and holds honorary D.Sc. degrees from the University of Paris and the University of Geneva. He is a member of the U.S. National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences.
C. Ronald KAHN
(Joslin Diabetes Center, Harvard Medical School, Boston)
Central role of insulin resistance in cardiovascular disease and the metabolic syndrome

The metabolic syndrome includes obesity, glucose intolerance, abnormalities in lipid metabolism, hypertension, hepatic steatosis and gallstones. The incidence of the metabolic syndrome and its various components is rising at epidemic rates. Using genetic and acquired animal models, we show that insulin resistance is central to the pathophysiology of metabolic syndrome. For example, a mouse with pure hepatic insulin resistance created by knockout of the insulin receptor in liver develops hyperglycemia due to increased hepatic glucose output and a dyslipidemia characterized by low HDL cholesterol, small dense LDL cholesterol, and marked sensitivity to diet induced hypercholestero-
lemia with severe atherosclerosis. Insulin resistance in other tissues, like the beta cell and brain, also contribute to the syndrome, with decreased insulin secretion, increased appetite leading to obesity, and other disorders. Thus, insulin resistance is sufficient to produce most of the features of the metabolic syndrome and serves as the best site for therapy of this disorder.
Central role of insulin resistance in cardiovascular disease and the metabolic syndrome
14:15   Discussion
14:25   Chairperson: Göran K. Hansson (Stockholm)

Helen H. HOBBS


Investigator of the Howard Hughes Medical Institute, Professor of Internal Medicine and Molecular Genetics at the University of Texas (UT) Southwestern Medical Center at Dallas

Helen Hobbs received her undergraduate degree from Stanford University and her medical degree from Case Western Reserve University. She trained in internal medicine and endocrinology at the UT Southwestern where she is now Director of the McDermott Center of Human Growth and Development. She is a member of the Institute of Medicine, of the American Academy of Arts and Sciences, and of the U.S. National Academy of Sciences. She received the Heinrich Wieland Prize and the 2007 Distinguished Scientist Award from the Heart Association.

She has used human genetics to elucidate key pathways in cholesterol and triglyceride trafficking and provided evidence that sequence variations with major effects collectively contribute significantly to common traits and diseases.
Helen H. HOBBS
(McDermott Center for Human Growth & Development, Dallas)
Rare mutations in complex diseases: not so rare and not so complex

Helen H. Hobbs and Jonathan C. Cohen. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas

Coronary atherosclerosis is a complex disease that results from multiple factors, both genetic and non genetic. We have taken a variety of approaches to test the hypothesis that rare sequence variations cumulatively contribute to complex traits and diseases in the general population. We have found rare and low frequency DNA sequence variations that impact on multiple traits that confer susceptibility (and resistance) to coronary atherosclerosis, including plasma levels of HDL-cholesterol, LDL-cholesterol and triglycerides. Such sequence variations provide a particularly powerful handle with which to dissect the relationships between genes, risk factors, and disease.
Rare mutations in complex diseases: not so rare and not so complex
15:10   Discussion
15:20   Break
15:35   Chairperson: Phillip Gorden (Bethesda)

Richard P. LIFTON


Investigator of the Howard Hughes Medical Institute, Sterling Professor of Internal Medicine, and Molecular Biophysics and Biochemistry at Yale University School of Medicine in New Haven

Richard Lifton received his B.A. from Dartmouth College, his M.D. and Ph.D. degrees from Stanford University, and was resident and chief resident in internal medicine at Brigham and Women’s Hospital. He has served as Chair of the NIH Advisory Committee for Large Scale Genomic Sequencing, a member of the Public Policy Committee of the American Society for Cell Biology and the U.S. National Advisory Council for the National Human Genome Research Institute. He is currently Chairman of the Department of Genetics at Yale University School of Medicine, Director of the Yale Center for Human Genetics and Genomics and Director of the Yale Specialized Center of Research in Hypertension. His awards include the Basic Science Prize of the American Heart Association, the Homer Smith Award of the American Society of Nephrology, the Novartis Award for Hypertension Research of the American Heart Association Council for High Blood Pressure Research, and the Medical Research Award of the Pasarow Foundation. He is a member of the U.S. National Academy of Sciences and the Institute of Medicine.

Dr. Lifton's laboratory has used molecular genetic analysis to dissect physiologic processes that regulate cardiovascular function in humans, with an emphasis on blood pressure regulation. By coupling characterization of hundreds of families from around the world with human genetic studies, his group has mapped over 30 human disease genes and has identified functional mutations underlying 22 of these. These have provided new insight into the mechanisms underlying hypertension, stroke, osteoporosis, and renal diseases including disorders of electrolyte and pH homeostasis.
Richard P. LIFTON
(Yale University School of Medicine, New Haven)
Genes, genomes and the future of cardiovascular diseases

Hypertension affects 1 billion people and is a major risk factor for stroke, myocardial infarction, congestive heart failure and kidney failure. By investigation of families with extreme forms of high or low blood pressure we have identified mutations in 10 genes that cause very high blood pressure and 10 that cause life-threatening low blood pressure. Most interestingly, the genes at both ends of the distribution are involved in renal salt handling - mutations that increase net renal salt re-absorption raise blood pressure, while those that reduce salt re-absorption lower blood pressure. Investigations of these same genes in the general population have shown that rare mutations have substantial effect on blood pressure and that these collectively are present in at least 2% of the population. Finally, these studies have identified a novel family of protein kinases, the WNK kinases, that are involved in regulating the balance between salt re-absorption and potassium secretion. These findings support early combination therapies that target the salt handling pathway and secondary compensatory mechanisms, and identify new therapeutic targets likely to be of high efficacy.
Genes, genomes and the future of cardiovascular diseases
16:20   Discussion
  
   

THURSDAY OCTOBER 9, 2008

    MORNING SESSION: 09:30 - 13:30
    Neuroscience: from patch clamp to cognitive functions
09:30   Chairperson: Michel Lazdunski (Valbonne Sophia Antipolis)

Bert SAKMANN




Photo: Svein Erik Dahl/Samfoto.
Emeritus Professor and Group Leader at the Max-Planck-Institute of Neurobiology in Martinsried

Dr. Bert Sakmann studied medicine in Tübingen, Paris, Berlin and Münich, and biophysics at University College London. He received is M.D. at the Medical Faculty of the University of Göttingen. In 1983, he rose to head the Membrane Physiology Unit and became Director of the Department of Cell Physiology at the Max-Planck-Institute for Biophysical Chemistry in Göttingen. In 1987, he was named a Professor at the Medical Faculty of the University of Göttingen. In 1989, he became Director of the Department of Cell Physiology at the Max-Planck-Institute for Medical Research in Heidelberg. In 1990, he was named a Professor at the Medical Faculty of the University of Heidelberg, and in 1991 a Professor at the Biological Faculty of this University. From 1999 to 2005, he was Laureate Professor under the Eminent Scholars Programme of the University of Melbourne (Australia).

Dr. Bert Sakmann is the recipient of numerous prizes namely the Louis-Jeantet Prize for Medicine (1988), the Gairdner Prize (1989), the Ernst Hellmut Vits Prize (1990), the Carus Medal (1991), the Harvey Prize (1991), the Gerard Prize (1991), the Landesforschungspreis Baden-Württemberg (1991), the Nobel Prize in Physiology or Medicine (1991) - most prizes jointly with Prof. Dr. Erwin Neher.
Bert SAKMANN
(Max-Planck-Institut für Neurobiologie, Martinsried)
Neurophysiology of decision making in the rodent brain

Decision making relies on sensory input, comparison with previous experience and motor action. A simple rodent behaviour is reward driven gap crossing. It can rely on the sensory input from a single vibrissa and exciting a single column in the barrel cortex. The major output emitted by a single column is by the thick-tufted pyramids in the infragranular layer that project to the pons. Possibly these pyramids establish the link between sensory input and motor action.
Neurophysiology of decision making in the rodent brain
10:15   Discussion
10:25   Chairperson: Christine Petit (Paris)

Thomas J. JENTSCH


Group Leader at the Max-Delbrück-Center for Molecular Medicine (MDC) and the Leibniz-Institute for Molecular Pharmacology (FMP) in Berlin

Thomas J. Jentsch received his Ph.D. in physics (1982) and his M.D. (1994) from the Free University Berlin. After investigating epithelial ion transport with Michael Wiederholt in Berlin, he joined the laboratory of H.F. Lodish at the Whitehead Institute (MIT) in Cambridge, where he began his work on the molecular biology of anion transport.
He cloned the first voltage-gated chloride channel in his own laboratory at the University of Hamburg in 1990 and unravelled the function of most members of this newly discovered gene family, using a combination of molecular cell biology, biophysics, knock-out mice, and human genetics.
Other areas of research include KCNQ potassium channels and KCC potassium-chloride cotransporters, again focusing on physiology, mouse pathologies, and human diseases. In 2006, he moved to Berlin and established his laboratory at the Max-Delbrück-Center for Molecular Medicine (MDC) and the Leibniz Institute for Molecular Pharmacology (FMP).

Thomas J. Jentsch is the recipient of numerous prizes including the Wilhelm-Vaillant Prize (1992), the Leibniz Prize (1995), the Alfred Hauptmann Prize and the Franz Volhard Prize (1998), the Zülch Prize (1999), the family Hansen Prize and the Louis-Jeantet Prize for Medicine (2000).
Thomas J. JENTSCH
(Max-Delbrück-Center for Molecular Medicine, Berlin)
Acid and chloride in endosomes and lysosomes: surprising insights from sick mice and men and from biophysics

Several CLC chloride transport proteins reside in membranes of endosomes and lysosomes. They are thought to facilitate their luminal acidification by neutralizing currents of the electrogenic proton pump. Loss-of-function mutations of vesicular CLC genes lead to diseases like kidney stones, osteopetrosis, and lysosomal storage disease in both men and mice. Whereas all CLC proteins were thought to be chloride channels like the founding member ClC-0 from the electric fish Torpedo, it is now clear that several, if not all vesicular CLCs are chloride/proton exchangers. These surprising new findings point to a previously unsuspected role of chloride in endosomes/lysosomes.
Acid and chloride in endosomes and lysosomes: surprising insights from sick mice and men, and from biophysics
11:10   Discussion
11:20   Break
11:40   Chairperson: Jean-Pierre Changeux (Paris)

Riitta HARI


Group Leader at the Helsinki University of Technology, Espoo, Finland

Professor Riitta Hari, M.D., Ph.D., was trained as a clinical neurophysiologist and received her degrees from Helsinki University. Since 1982, she leads the Brain Research Unit (BRU) of the Low Temperature Laboratory and since 2003 the Advanced Magnetic Imaging Centre at the Helsinki University of Technology. She currently directs the National Centre of Excellence on Systems Neuroscience and Neuro-imaging, appointed by the Academy of Finland. She is a member of the U.S. National Academy of Sciences, of the Academia Europaea, and of the Finnish Academy of Sciences and Letters. She received the Louis-Jeantet Prize for Medicine in 2003.

Since the early 1980s, Professor Hari’s research team has been developing magneto-encephalography (MEG) with a broad scope, including new instruments, sophisticated signal analysis methods, with a special focus on studies of all sensory systems and of various cognitive brain functions of healthy subjects and of various patient groups. Professor Hari’s main interest is in temporal dynamics of human cortical functions, most recently related to the brain basis of social interaction.
Riitta HARI
(Helsinki University of Technology, Espoo)
Do we need two-person neuroscience?

We are born into a social world constructed and interpreted by others. During our whole life, we interact with other people, constantly trying to figure out their intentions and actions. In this lecture I will argue that to properly study the social shaping of the human brain (and mind), we should progress from one-person neuroscience to two-person neuroscience. A great challenge is to build a new conceptual framework that incorporates neuroscience, psychophysiology, and social sciences. Novel methods are needed for online and time-synchronized monitoring of two individuals during real-life-like social interaction. To appreciate the bridge between brain and body, both brain signals and autonomic nervous activity should be recorded from the interacting partners.
The two-person neuroscience will have applications in characterizing and treating disorders of social interaction, as well as in monitoring and improving master-apprentice and patient–therapist relationships. It can also contribute to old philosophical questions, such as intersubjective understanding.
Do we need two-person neuroscience?
12:25   Discussion
12:35   Closing conference
Chairperson: Piet Borst (Amsterdam)

Paul NURSE


President of The Rockefeller University in New York

Paul Nurse, FRS, who shared the 2001 Nobel Prize in Physiology or Medicine, became President of The Rockefeller University in September 2003. He had previously served as Chief Executive of Cancer Research UK, the largest cancer research organization in the world outside the United States. Dr. Nurse is noted for his discoveries about the molecular machinery that regulates the cell cycle, the process by which a cell copies its genetic material and then divides to form two cells.
In addition to the Nobel Prize, Dr. Nurse has received the Albert Lasker Award for Basic Medical Research, the Gairdner Foundation International Award, the Louis-Jeantet Prize for Medicine, the Royal Society’s Wellcome and the Royal and Copley medals, amongst other scientific awards. A fellow of the Royal Society, he is a founding member of the U.K. Academy of Medical Sciences, a member of the American Academy of Arts and Sciences, and a foreign member of the U.S. National Academy of Sciences. He was knighted in 1999 and received France’s Légion d’Honneur in 2002.
Dr. Nurse plays an active role in science and society issues and makes regular TV appearances including as a co-host for a science series on PBS.
Paul NURSE
(The Rockefeller University, New York)
Controlling the cell cycle

The growth and reproduction of all living organisms are dependent on the cell cycle, the process which leads to cell division. Uncontrolled division of cells is important for disease particularly cancer. Two events, S-phase and mitosis, are common to all cell cycles and are necessary for the two newly divided cells to receive a full complement of genes. The onset of S-phase and mitosis are controlled by cyclin dependent kinases in all eukaryotes studied from yeast to human beings. Checkpoints controls working through the CDKs block cell cycle progression if cells are too small or DNA incompletely replicated.
Controlling the cell cycle
13:30   Lunch
 

 

14:30   2008 Louis-Jeantet Awards Ceremony
16:30   Refreshments