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Speakers









-> Stephan Beck

Department:

Medical Genomics

Email:

Web Page:

http://www.ucl.ac.uk/cancer/research-groups/medical-genomics/

Institute:

UCL Cancer Institute



Research title:

Medical Genomics

In addition to polymorphisms and mutations, we study epigenetic changes such as DNA methylation and histone modifications that can modulate genome function under exogenous influence. Central to our research is the development an integrated systems approach - termed 'reverse phenotyping' - to screen genomes of common diseases as well as cancer for genetic, epigenetic and combinatorial variations. The ability to distinguish causal from consequential variations is one of the key challenges in biomedical research. Once fully established, 'reverse phenotyping' can be expected to significantly increase our ability to identify novel and, in particular, combinatorial variations causing or contributing to phenotypic plasticity and thus will provide new targets for translation into diagnostics and therapeutics. The laboratory offers state-of-the-art facilities and a stimulating environment for graduate and post-doctoral training.

For publications, please see:

www.ucl.ac.uk/cancer/research-groups/medical-genomics/publications/



-> Wolfgang Hammerschmidt

Department:

Department of Gene Vectors

Email:

/

Web Page:

http://www3.gsf.de/GENV/

Institute:

Helmholtz Zentrum München-Haematologikum



Research title:

EBV Genetics & Vectors

Epstein-Barr virus (EBV) is an outstanding human herpes virus that readily infects human B-lymphocytes in vitro and in vivo. Epstein-Barr virus was the first human tumor virus to be discovered and is classified as a group 1 carcinogen by the World Health Organization (WHO). This virus is strongly associated with a number of human tumors such as nasopharyngeal carcinoma, gastric cancer, Burkitt’s lymphoma, immunosuppression-related lymphomas, Hodgkin’s disease, and others. Upon infection of normal resting human B-lymphocytes the virus establishes a latent (i.e. non-productive) infection and induces the indefinite proliferation of the infected cells. These biological characteristics are reminiscent of some (but not all) aspects of tumor etiology in man and serve as a tractable model system for human tumors in vitro.

 

 









-> Matthew Weitzman

Department:

Laboratory of Genetics

Email:

Web Page:

http://www.salk.edu/faculty/weitzman.html

Institute:

The Salk Institute for Biological Studies



Research title:

Virus Interactions with the Cellular DNA Repair Machinery

Our lab studies the interactions between viruses and their host cells. Viruses try to hijack cellular machinery to aid their own replication, but the host cell often responds with defense systems that can create obstacles for the virus. Watching these battles unfold has contributed significantly to our understanding of fundamental cellular mechanisms and has established viruses as powerful model systems to study cell biology. We have a particular interest in the interactions between viruses and the DNA repair pathways of the host cell. Cells have complex machineries in place to monitor and repair damage to their own genomes. We recently discovered that the cell often recognizes the foreign viral genome as damaged DNA. This results in the cell mounting a cascade of signaling events in an attempt to “repair” the viral DNA. This can have a deleterious outcome for some viruses while others can counterattack by dismantling the cellular DNA repair machinery or even exploiting it to aid their own replication. Knowledge from viral systems can also be harnessed to alter the genetic makeup of cells.

 

 









-> Charles R. Bangham

Department:

Faculty of Medicine Immunology

Email:

Web Page:

Prof Charles R M Bangham

Institute:

Imperial College London


Research title:

The cellular immune response to infection with the human

leukaemia virus HTLV-1

 

 









- > Jeremy Luban

Department:

Department of Microbiology and Molecular Medicine

Email:

Web Page:

http://www.mimo.unige.ch/luban_lab/

Institute:

http://www.unige.ch/



Research title:

Viral replication, pathogenesis and immunity

The simplicity of the HIV-1 genome renders replication of this virus dependent upon host cell machinery. Similarly, pathology associated with HIV-1 infection results from interactions among cellular factors and the nine HIV-1 genes. Using genetic and biochemical techniques we identify host cell factors that contribute to viral replication, pathogenesis, and immunity. In the process we exploit HIV-1, using the virus as a probe of basic cellular functions including cytokinesis, protein-folding, genetic recombination, recognition of non-self, signal transduction, and cytokine expression. Our research is basic in nature but by shedding light on mechanisms of HIV-1 replication and immune system evasion we hope to contribute to the development of drugs and vaccines that target this virus, as well as other disease states.

 

 









- > Sigrun Smola

Department:

Institute of Virology

Email:

Web Page:

Institute of Virology

Institute:

Saarland University Hospital



Research title:

In the field of clinical virology, the Institute of Virology provides diagnostic services for all relevant virus infections to the university hospital. We are also concerned with problems in immunology and latency and reactivation of persistent herpes infections of herpes group viruses (HSV, VZV, CMV, EBV, HHV6, 7, 8) in immunosuppressed patients. National and international recognition of the institute’s work on lymphotropic herpes viruses has led to the Federal Ministry of Health designating the institute as a “National Advisory Laboratory for EBV and HHV6, 7 and 8”. Our institute, together with the Institute of Microbiology and Hygiene, also acts as the “Centre for Medical Analysis” for the state of Saarland, whose key tasks include the prevention of contagious diseases and biological weapons and diagnostic procedures for pathogens that pose a risk to public health.




 

 









- > Judy Breuer

Department:

Centre for Infectious Disease

Email:


Web Page:

click here

Institute:

Barts and The London School of Medicine and Dentistry, London. UK



Research title:

A human approach to understanding VZV disease

Varicella zoster virus  (VZV), a member of the alphaherpesviridae subfamily is the cause of two diseases, chickenpox and shingles.  A live attenuated vaccine is to prevent chickenpox licensed for use in many countries.  VZV is almost exclusively a human pathogen and no good animal model of VZV disease exists.  This presents challenges to the study of its pathogenesis, which can only be partially overcome by in vitro and SCID-hu mouse models. We have made use of VZV genetic variation in both wild type and vaccine strains of VZV together with molecular epidemiological tools, to characterise spread of VZV and to try to  identify genetic determinants of infection particularly in skin.  The work has led to a better understanding of the diverse global epidemiology of chickenpox and has allowed us to develop molecular tools with which to explore VZV pathology.




 

 

 







- > Felix Rey






Department:

Virology Department


Email:



Web Page:

click here


Institute:

Institut Pasteur, Paris, France





Research title:

3D structures of viral envelope proteins and insights into their role as membrane fusogens.









The surface glycoproteins of enveloped viruses carry essential functions during the virus cycle. They are the main targets of the humoral immune response and thus carry the principal antigenic determinants of the virus. The envelope proteins also display important activities during budding of newly formed particles, and during the process of entry of the virus into a new cell. For virus entry, they interact both with attachment and entry receptors. The former leads to concentration of virus particles at the cell surface, often via low-affinity interactions and in a non-specific manner. In contrast, binding to entry receptors usually involves a specific, high-affinity interaction, which results in endocytosis or in a direct fusogenic conformational change in the envelope protein. Membrane fusion - the second function of the envelope proteins – which occurs downstream in the sequence of events during entry - is needed to allow the virus genomic information to be released into the cytoplasm of the target cell. It involves an important conformational change of the envelope protein, such that it exposes a previously buried segment of the polypeptide chain, termed “fusion peptide” or “fusion loop”, which interacts with the target membrane. Structural studies of viral envelope proteins have revealed that they can be classified into three structural “classes”, and that these classes appear to operate by essentially the same molecular mechanism. All of the fusion proteins characterized structurally are type I membrane proteins, with a large ectodomain containing the N-terminus, and are attached to the viral membrane via a C-terminal segment, which is loosely connected to the rest of the protein. Interactions with the target cell – either entry receptor binding, or proton binding upon endocytosis into endosomes at acidic pH – disturb the pre-fusion oligomer such that it undergoes a fusogenic conformational change. This change first leads to exposure of the fusion loop away from the virion, such that it can bind to the target cell membrane. This step is followed by an important refolding of the protein, such that the fusion loop is brought into juxtaposition with the C-terminal membrane anchor of the protein, thus forcing the target and viral membrane to come very close to each other. Furthermore, lateral contacts between fusogenic proteins induce strong curvature changes in destabilization of the target membrane, thus catalysing fusion of the two bilayers. The refolding energy released during the fusogenic conformational change is used to drive lipid merging. My talk will summarize the major mechanistic insights into the membrane fusion reaction induced by enveloped viruses provided by structural studies.