Monday 9 and Tuesday 10 June 2008
Organised by Dr Patricia Gearhart, Dr Tomas Lindahl FRS and Dr Michael Neuberger FRS
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Professor Fred Alt (speaker)
Frederick Alt received his Ph.D. in Biology from Stanford in 1977 where he worked with Robert Schimke and discovered gene amplification in anti-cancer drug-resistant mammalian cells. Alt moved to MIT for postdoctoral work with David Baltimore, where elucidated basic principles of recombination events in the immune system. In 1982, Dr. Alt moved to Columbia University as an Assistant Professor of Biochemistry and became Professor of Biochemistry and Molecular Biophysics in 1985 and a Howard Hughes Medical Institute Investigator in 1987. At Columbia he continued his work on genomic instability and cancer and also on B cell development. In 1991, Dr. Alt moved to Harvard Medical School as a Professor of Genetics and Pediatrics, an HHMI Investigator at Boston's Children's Hospital and a Senior Investigator at the Immune Disease Institute (formerly known as CBR Institute for Biomedical Research). He was appointed Charles A. Janeway Professor of Pediatrics in 1993 and Scientific Director of the Immune Disease Institute in 2005. In Boston, his group played an major role in elucidating the non-homologous DNA end-joining (NHEJ) pathway of DNA double strand break repair and he has continued his work on V(D)J recombination and IgH Class Switch Recombination. In 1994, Dr. Alt was elected to the U.S. National Academy of Sciences, the American Academy of Arts and Sciences, and the American Academy of Microbiology; in 1999 he was elected to EMBO as a foreign associate. In 2004, Alt received the Clowes Memorial Award from the American Association of Cancer Research; in 2005 he received the Rabbi Shai Shacknai Prize from The Hebrew University, the Pasarow Foundation Prize in Cancer Research, the Leukemia & Lymphoma Society de Villiers International Achievement Award, and the Irvington Institute Immunology Award. In 2007, Alt received the National Cancer Institute Alfred K. Knudson Award; the American Association of Immunologists AAI-Huang Meritorious Career Award, and the Novartis Prize in Basic Immunology. Dr. Alt has mentored over 100 students and research fellows and he received the 2003 American Association of Immunologists Excellence in Mentoring Award.
Professor Jean-Marie Buerstedde (speaker)
Jean-Marie Buerstedde studied medicine in Kiel, Madrid and Göttingen and received his M. D. in 1985. He completed his postdoctoral studies at the Department of Immunolgy at the Mayo Clinic in Rochester, MN in the group of David McKean. He then worked as a member of the Basel Institute for Immunology from 1988 until 1998. Since 2002 he is head of the Institute of Molecular Radiation Biology at the Helmholtz Center Munich. His main interest is the mechanism of immunoglobulin gene diversification in B cells. In 1991 he reported in collaboration with Shunichi Takeda that the chicken B cell line DT40 integrates transfected DNA constructs by homologous recombination into its genome leading to the widespread use of this cell line for gene function analysis. In 2001 the laboratory demonstrated that immunoglobulin gene conversion is dependent on the expression of the activation induced cytidine deaminase AID which was previously shown to be required for immunoglobulin hypermutation and switch recombination. Research in the laboratory currently focuses on the mechanism that limits AID mediated gene diversification to the immunoglobulin loci of B cells.
Dr Anne Durandy (speaker)
I was born in Verdun, France 12/13/1948. I begun medical studies in Paris at University Paris V and obtained my M.D in 1974. Thereafter I joined the lab created by Pr. C. Griscelli at Hopital Necker and devoted to the study of lymphocyte development in normal and pathological conditions. I got a permanent research position at INSERM in 1978 and obtained my Ph.D in 1984. My main interest was the study of immune response in fetal life and the description of new inherited immunodeficiencies. From 1993, in the lab then directed by Pr. A. Fischer, I have been essentially interested in Ig-class switch recombination (CSR) defects. I participated to the description of CD40L and CD40-deficiencies. I described that the activation-induced cytidine deaminase and the uracil-N glycosylase are essential for CSR in humans. I am still involved in CSR mechanisms through the study of patients affected by CSR-defects.
Dr Patricia Gearhart (organiser)
Dr. Patricia J. Gearhart received her Ph.D. in immunology from the University of Pennsylvania in 1974, where she studied antibody repertoires with Norman Klinman. She performed postdoctoral training at the Johns Hopkins University with John Cebra, and examined IgA responses in secretory tissues. Dr. Gearhart was a staff associate at the Carnegie Institution of Washington in Baltimore until 1982, where she showed that amino acid substitutions in antibodies were caused by somatic hypermutation of DNA. She then became a faculty member at the Johns Hopkins University, and demonstrated that the mutations were localized to a small region around rearranged variable genes. In 1995, she joined the Laboratory of Molecular Gerontology at the National Institute of Aging, and has shown that mismatch repair proteins and low-fidelity DNA polymerases participate in the hypermutation pathway.
Professor Myron Goodman (speaker)
Myron F. Goodman performed graduate studies at Johns Hopkins University and received a Ph.D. in Electrical Engineering in 1968. His thesis investigated a theory of laser interactions with complex polyatomic molecules with an eye toward achieving non-thermal laser-induced bond selective chemistry. Instead of starting a career at Bell Laboratories, he made the somewhat peculiar choice of switching gears to study the biochemistry of DNA polymerases as a postdoctoral associate with Maurice J. Bessman at Johns Hopkins. In 1973, he joined the faculty at the University of Southern California, in the Department of Biological Sciences, and divided efforts between developing a theory of laser stimulated decomposition of molecules, which led to infrared laser-driven separation and enrichment of isotopes of uranium, and studies on the fidelity of DNA polymerases and SOS mutagenesis. A study to model SOS mutagenesis in vitro, which involved an exceptionally pleasant and fruitful collaboration with Hatch Echols at Berkeley, resulted in the discovery of the "sloppier copier" E. coli DNA polymerase V. His current research is focused on the role of activation-induced cytidine deaminase in somatic hypermutation of immunoglobulin genes, the biochemical basis of SOS mutagenesis involving pol V and RecA protein, and the "inner workings" of DNA polymerases that determine their fidelity.
Professor Warner Greene (speaker)
Warner C. Greene, MD, PhD is Director, and Nick and Sue Hellmann Distinguished Professor of Translational Medicine of the Gladstone Institute of Virology and Immunology (GIVI) and is Professor of Medicine, Microbiology and Immunology at the University of California, San Francisco (UCSF). Dr. Greene also serves as co-director of the UCSF-GIVI Center for AIDS Research. His research focuses on studies of the molecular basis for HIV and HTLV-I retroviral pathogenesis and the biochemical mechanisms underlying the regulation and action of the NF-B/Rel family of eukaryotic transcription factors. The author of more than 300 scientific papers, Dr. Greene has been honored by outstanding investigator awards from the American Federation for Clinical Research and the American College of Rheumatology and has been recognized as one of the 100 most-cited scientists in the world. He is a fellow of the American Academy for the Advancement of Science, a Councilor of the Association of American Physicians, and a member of the Institute of Medicine of the National Academies. In 2007 he became President of the Accordia Global Health Foundation, whose mission is to build alliances to fight infectious disease in Africa.
Professor Tasuku Honjo (speaker)
Tasuku Honjo graduated from Kyoto University Faculty of Medicine in 1966 (M.D.). After postdoctoral training in U.S., he took position in Tokyo, Osaka, and Kyoto. Currently, he is Professor of Department of Immunology and Genomic Medicine, Kyoto University and also Executive Member of Council for Science and Technology Policy, Cabinet Office.
Dr. Honjo is well known for his discovery of activation-induced cytidine deaminase that is essential for class switch recombination and somatic hypermutation. He has established the basic conceptual framework of class switch recombination starting from discovery of DNA deletion (1978) and S regions (1980), followed by elucidation of the whole mouse immunoglobulin heavy-chain locus. His contribution further extended to cDNA cloning of IL-4 and IL-5 cytokines and PD-1 (program cell death 1), a negative coreceptor at the effector phase of immune response.
Honored by the Japanese Government as a person of cultural merits (2000). Elected as a foreign associate of National Academy of Sciences, USA in 2001, as a member of Leopoldina, the German Academy of Natural Scientists in 2003, and also as a member of Japan Academy in 2005.
Professor Joseph Jiricny (chair)
Josef Jiricny was born in Prague in 1951. He emigrated to England in 1969, where he studied chemistry, first in Birmingham, then in London. He obtained his PhD in 1977. His postdoctoral studies were devoted to studying the chemical synthesis of DNA at London's King's College. As a research fellow at the Imperial Cancer Research Fund laboratories in London, he began to study repair mechanisms of damaged DNA. In 1983 he joined the Friedrich Miescher Institute in Basel, where he was the first to identify human mismatch repair proteins. In 1990 he became director of biochemistry at the Istituto di Ricerche di Biologia Molecolare in Rome, where he helped elucidate the mechanistic basis of Hereditary Non-Polyposis Colon Cancer. In 1996 he became director of the Institute of Molecular Cancer Research of the University of Zürich. He is also a Bonizzi-Theler professor at the Swiss Institutes of Science and Technology (ETH).
Professor Hans Krokan (speaker)
Hans E. Krokan is MD from University of Oslo and PhD in biochemistry from University of Tromsø, Norway. His early work concentrated on mechanisms of DNA replication. Later he has concentrated on mechanisms of DNA repair in mammalian cells. He joined Norwegian University of Science and Technology as a professor in1988 and is chairman of Department of Cancer Research and Molecular Medicine. His most important contributions are within repair of uracil-containing DNA and repair of methylation lesions. His group has carried the research all the way from protein purification to human disease. In addition, the laboratory has a strong and growing activity within association between common single nucleotide polymorphisms and human cancer. Dr. Krokan is an honorary member of The Norwegian Biochemical Society, member of EMBO and member of The Norwegian Academy of Science and Letters. In 2004 he received The Anders Jahre Prize for Medical Research.
Professor Alan Lehmann (chair)
Alan Lehmann has carried out research for many years into the mechanisms of DNA repair and its relationship to human genetic disorders. His most significant contribution has been the insights he has provided into the way in which cells are able to replicate damaged DNA. He showed that xeroderma pigmentosum variant patients were defective in this ability, he characterised numerous aspects of this process and showed how a specialised DNA polymerase is employed to replace the replicative polymerase blocked at DNA damage. His work also revealed DNA repair defects in Cockayne Syndrome, trichothiodystrophy and a form of immunodeficiency. In addition he has elucidated the molecular architecture and functions of the Smc5-6 DNA repair complex. He is a Fellow of the Academy of Medical Sciences.
Dr Michael Malim FRS (speaker)
Michael Malim is Professor and Head of the Department of Infectious Diseases at the King's College London School of Medicine. His laboratory utilises molecular genetic, cultured cell, biochemical and structural methods to study the biological principles that underpin HIV replication and pathogenesis (AIDS). Current areas of focus include host-virus interactions, natural mechanisms of anti-viral resistance and virus particle assembly.
Dr Malim received his DPhil from Oxford University in 1987, and was then a post-doctoral fellow at Duke University before joining the faculty at the University of Pennsylvania in 1992. After nine years in Philadelphia, Dr Malim returned to his native U.K. to assume his current positions.
Dr Malim's research has spanned multiple facets of the HIV replication cycle, including viral RNA processing and nuclear export, virus particle assembly, infection of non-proliferating cells and the role(s) played by the regulatory/accessory proteins of HIV. In recent years, much of his group's work has been devoted to the viral protein Vif; and it was through these efforts that the human anti-HIV gene APOBEC3G was identified. This protein exhibits a novel and potent antiviral effect that is associated with the destructive mutation of HIV DNA by a process called cytidine deamination. Though Vif is an effective antagonist of APOBEC3G function, it is hoped that perturbation of this regulatory interface can be exploited for the development of future anti-HIV/AIDS therapeutics.
Dr Michael Neuberger FRS (organiser)
Michael Neuberger is Joint Head of the Protein and Nucleic Acid Chemistry Division at the Medical Research Council Laboratory of Molecular Biology in Cambridge. He graduated in biochemistry from the University of Cambridge in 1974, carried out a PhD with Brian Hartley at Imperial college, London in the area of bacterial genetics, spent a postdoctoral year supported by an EMBO fellowship with Klaus Rajewsky in Cologne where he learned immunology and then returned to Cambridge to work at LMB, since when he has continued to carry out research into various aspects of antibody gene expression, diversification, signaling and engineering.
Professor Laurence Pearl FRS (speaker)
Laurence Pearl is Professor of Crystallography and Chairman of the Section of Structural Biology at the Institute of Cancer Research, Chester Beatty Laboratories in Chelsea. He began his research career at Birkbeck College working with Tom Blundell, and after Postdoc research at ICR Sutton, started his own laboratory at UCL in 1989 as a Lecturer in Biochemistry, becoming Professor of Structural Biology in 1996. He joined ICR in 1999, where his laboratory studies the structural biology of DNA repair, signal transduction and molecular chaperones. he is a member of EMBO, a Fellow of the Academy of Medical Sciences, and was elected Fellow of the Royal Society this year.
Dr Svend Peterson-Marht (speaker)
Dr Petersen-Mahrt received his PhD from Boston University in 1996, for his work on chimerae-antibody engineering. He then moved to Uppsala, Sweden joining the lab of Dr. Göran Akusjärvi as a Wenner-Grenska research fellow, to study the regulatory mechanisms of alternative mRNA splicing. In 1999, with an EMBO fellowship, he returned to the studies of immunoglobulins, and began research to elucidate the molecular aspects of somatic hypermutation in the lab of Dr. Michael Neuberger at the MRC-LMB in Cambridge. While in the lab, he co-identified the mechanism of protein derived DNA deamination, and has continued working in this area ever since. In late 2003 he became an independent group-leader at the Cancer Research UK core funded Clare Hall Laboratories north of London, working on the the function of DNA deaminases within and outside the immune system.
Dr Claude-Agnès Reynaud (speaker)
Claude-Agnès Reynaud is Director of Research at CNRS, head of INSERM unit "Développement du système immunitaire" at the Faculté de Médecine Necker-Enfants Malades, Université Paris Descartes. After finishing her PhD on the processing of avian globin pre-mRNA, she and Jean-Claude Weill joined in 1981 to study immunoglobulin gene diversification, describing gene conversion in chickens and somatic mutation in sheep as mechanisms generating the pre-immune repertoire in these species, first at the Institut Jacques Monod (Université Paris Diderot), then at the Basel Institute for Immunology. They are now involved in studying the role of non-replicative polymerases in immune diversification processes, as well as B cell diversification pathways in humans.
Dr Julian Sale (speaker)
Dr Sale reads medicine at the University of Cambridge, qualifying in 1991 after which he practised in East Anglia and Nottingham, gaining Membership of the Royal College of Physicians in 1994. He undertook a PhD at the Laboratory of Molecular Biology in Cambridge working on immunoglobulin somatic hypermutation under the supervision of Michael Neuberger. Dr Sale was subsequently awarded an MRC Clinician Scientist Fellowship, the latter part of which he used to start his own group at LMB in 2001 working on mechanisms of DNA damage tolerance and mutagenesis in vertebrates. He teaches Pathology at Gonville & Caius College having won a College Research Fellowship in 1999, and was appointed Director of Studies in Medicine in 2001.
Professor Janet Stavnezer (speaker)
Professor Janet Stavnezer received her Ph.D. in Biochemistry in Dr Ru-Chih Huang's laboratory at Johns Hopkins University in Maryland, and did postdoctoral research in Dr J.Michael Bishop's laboratory at the Univ of California Medical School in San Francisco. She moved to Memorial-Sloan-Kettering Institute in New York for her first faculty position, and then to the University of Massachusetts Medical School in 1985. Since the beginning of her research career she has been investigating how antibodies are encoded in the genome, first
identifying and characterizing the mRNA for immunoglobulin light chain during her training years, and then she began the studies which engage her still today, to investigate the regulation and mechanism of immunoglobulin class switch recombination.
Professor Simon Wain-Hobson (speaker)
Head of Molecular Retroviral Unit at Institut Pasteur. EMBO 1997; Academia Europaea 2007; André Lwoff Prize 1997; Athena Prize, French Academy of Sciences 2006. I started in undergraduate chemistry because of a good school teacher. However, I soon realized that biology was far more interesting. An Oxford DPhil in biochemistry and an immunology post doc at the Weizmann Institute got me into the exploding field of molecular biology. A second post doc at the Pasteur Institute saw the shift to HBV. The timing was perfect for the Barré-Sinoussi et al. paper describing the isolation of HIV in 1983. The past 24 years have been devoted to the genetics of HIV starting with the molecular cloning of the virus back in 1984 and subsequent sequencing of a full-length clone. The inherent variation and the ability of the virus to absorb so much change while remaining devastating functional never ceases to amaze.
Professor Robin Weiss FRS (chair)
Robin Weiss is Professor of Viral Oncology at University College London. He gained a BSc and PhD at UCL. He has spent most of his career studying retroviruses, contributing to the discovery of viral genomes inherited as Mendelian traits in host DNA. In the 1970s, he worked with Peter K Vogt in USA and at the Imperial Cancer Research Fund, London. From 1980-1989 he was Director of the Institute of Cancer Research, Royal Marsden Hospital, and he returned to UCL in 1999. Robin has pioneered aspects of our understanding of HIV and AIDS, particularly the identification of CD4 as the HIV receptor and the analysis of neutralizing antibodies. He has also conducted research on AIDS-associated malignancies, and on pig viruses in relation to xenotransplantation. He is currently President of the Society for General Microbiology.