Select a year 2001 2002 2003    Select a researcher Alan G. Barbour, M.D. William Bishai, M.D., Ph.D. Martin J. Blaser, M.D. John C. Boothroyd, Ph.D. Jon Clardy, Ph.D. Peter Cresswell, Ph.D. Roy Curtiss, III, Ph.D. Ronald W. Davis, Ph.D. Jack E. Dixon, Ph.D. Stanley Falkow, Ph.D. Gerald R. Fink, Ph.D. Richard A. Flavell, Ph.D. Lee Gehrke, Ph.D. Laurie H. Glimcher, M.D. Jeffrey I Gordon, M.D. Daniel L. Hartl, Ph.D. William R. Jacobs, Jr., Ph.D. Keith A. Joiner, M.D., co-PI Karla Kirkegaard, Ph.D. Roberto G. Kolter, Ph.D. W. Ian Lipkin, M.D. Richard M. Locksley, M.D. Carl Nathan, M.D. Peter Palese, Ph.D. Pradipsinh K. Rathod, Ph.D. David A. Relman, M.D. Charles M. Rice, Ph.D. Alexander Rich, M.D. Lee W. Riley, M.D. David S. Roos, Ph.D. Abigail A. Salyers, Ph.D. Gary K. Schoolnik, M.D. Iwona Stroynowski, Ph.D. Ronald P. Taylor, Ph.D. Elisabetta Ullu, Ph.D. John Waitumbi, D.V.M., Ph.D Select a project A Gnotobiotic Zebrafish Model for Analyzing Symbiotic Host...Antiviral Effects of Interferon-Inducible Cytosolic ProteinsArming the Immune System against Pathogens with Selective ...Bacterial Pathogen Families that Function in Both the Anim...Cellular Genes and Viruses: Who Wins The War?Conditional Targeted Deletions in Plasmodium falciparum...Designing and Mining Pathogen Genome Databases: The Apicop...Development of Genetic Systems for Genetically Intractable...Development of New Genetic Tools to Identify Nutrient Upta...Ecological Influences on Pathogen Genome EvolutionEvolution of Virulence in Eukaryotic PathogensExploiting an Evolutionary Omission in Pathogenic RNA Viru...Exploring Novel Pathways of Immune Defenses Against Orally...Genomic Approach to Improved Immunogenicity of M. tuber...Genomic tools to characterize hypermutating Plasmodium fal...Investigation of Mechanisms Leading to Anemia at Low Paras...Molecular definition of the bacterial population of human ...Mycobacterium Tuberculosis Latency and Reactivation Tuberc...New Antibiotics from Environmental DNAOptimizing Immunity to Complex Pathogens In VivoPandora's Box ProjectProviding an Economic Benefit to Using a Vaccine to Enhanc...Resistance Gene Flow in the Human Colonic MicrofloraRole of Nucleotide Binding Domain-Leucine Rich Repeat Prot...Sexually Transmitted Disease Agents in the “Healthy” Human...Systematic Analysis of Positive-strand RNA Viral Transmiss...The Human Intestinal Microbiome: Community Analysis, Host ...The Molecular Ecology of Vibrio cholerae in the Gangetic D...The Natural History of Typhoid Infection in VietnamThe Role of Quorum Sensing in Fungal DiseaseTowards Broad-spectrum Antivirals: Functional Screens for ...Transmission Blocking Vaccines for TuberculosisTransmission-blocking Vaccines Against Arthropod VectorsViral Pathogenic Mechanisms Involving Z-DNA Binding Proteins Select an institution Albert Einstein College of Medicine of Yeshiva University Columbia University Harvard Medical School Harvard School of Public Health Harvard University Johns Hopkins School of Public Health Massachusetts Institute of Technology Mount Sinai School of Medicine New York University School of Medicine Rockefeller University Stanford University School of Medicine Stanford University School of Medicine, VA Palo Alto Health Care System University of California - Berkeley University of California - Irvine University of California - San Diego University of California - San Francisco University of Illinois - Urbana-Champaign University of Pennsylvania University of Texas Southwest Medical Center University of Virginia University of Washington Washington University Washington University School of Medicine Weill Medical College of Cornell University Whitehead Institute for Biomedical Research Yale University School of Medicine

Alexander Rich, M.D. Massachusetts Institute of Technology

Recently, this laboratory has uncovered a new mechanism that is used by poxviruses such as vaccinia or its cousin variola, the agent of smallpox. This mechanism is used by the virus to disarm the host cell. When the host cell manufactures proteins used for fighting the infection, it turns on genes that are found in its DNA. When genes express proteins, a segment of the DNA is often twisted into a left-handed fold, as opposed to normal, relaxed DNA which twists in a right-handed manner. The segments of DNA that twist left-handed are often near the beginnings of genes. These viruses have discovered that if they make proteins that bind to these left-handed-twisting segments, they can block the host cell from synthesizing some of the proteins used to fight infection.

The question we are asking in this research is whether this mechanism, which was identified in poxviruses, is also found in other viral systems. We will analyze other viruses to see if they make some proteins that bind to left-handed-twisting DNA since they may also act to prevent the host from responding to the infection. Uncovering these proteins will be of great value as they can then be used as targets, that is, drugs can then be developed that attach to the proteins, preventing them from binding to the left-handed DNA molecules. In this way the host defense machinery is not blocked, and it can then mount an effective response against the virus. This may result in the development of new therapies for viral diseases.