Schedule for 2011 - 2012
Professor
Division of Environmental & Biomolecular Systems
Oregon Health & Science University
Title: Activation of transcription by Spx and its role in the bacterial stress response
Abstract: Bacteria encounter harsh environmental conditions, to which they must respond appropriately to ensure survival. The transcriptional regulator, Spx, is essential for survival of Bacillus subtilis under oxidative stress and encounters with toxic agents. Spx is highly conserved in low-GC-content Gram-positive bacteria, including some pathogens in which it serves as a virulence determinant. The N-terminus of Spx contains a CXXC motif that acts as a thiol-based redox switch that affects Spx-dependent transcriptional control. Under oxidative stress, the amount of Spx protein increases due to the de-repression of the spx gene and reduced proteolysis of Spx protein. Meanwhile, the intra-molecular disulfide bond forms between the cysteine residues in CXXC motif, and the oxidized form of Spx activates transcription initiation of genes such as trxA (thioredoxin) and trxB (thioredoxin reductase) and over 120 other genes. However, the detailed mechanism by which Spx activates gene transcription is still unknown. Structurally, Spx resembles the enzyme arsenate reductase, but it regulates gene transcription through the interaction with C-terminal domain of the RNA polymerase (RNAP) α subunit. It shows no DNA-binding activity of its own, however. The seminar will present our studies of Spx-dependent transcription activation, proteolytic control of Spx, and the role of Spx in the stress response.
Host: Jose Lemos
Sponsored by the Immunology Training Grant.
Member
Trudeau Institute
Title: Dissecting Cytokine Responses in vivo
Seminar Abstract: Cytokines are soluble messenger molecules that mediate the communication between the diverse immune cell subsets in health and disease. The production and functional potential of cytokines are regulated at multiple levels in both the producing cell as well as the responding populations. Due to their rapid secretion it is inherently difficult to identify cytokine-expressing cells, particularly in vivo. To overcome this obstacle we have in recent years engineered various cytokine reporter mice that enable us to directly visualize cytokine-expressing cells. One focus of our research are T helper (Th2) 2-polarized CD4 T cell responses which are generated in response to infection with gastrointestinal helminth parasites but are also associated with allergic and asthmatic disorders. Interleukin (IL)-4 is the signature cytokine of Th2 cells and we explore the basic cellular and molecular mechanisms governing the immune regulation of and by IL-4. Using IL-4 dual reporter mice we have revealed an intriguing choreography underlying the induction and maintenance of Th2 responses
Host: Deborah Fowell
Professor of Biochemistry and Molecular Biology,
Affiliate, , Division of Immunology & Pathogenesis
University of California at Berkeley
Title: Forward genetics to identify microbial components that activate host cytosolic surveillance pathways
Seminar Abstract: How does the innate immune system discriminate between pathogenic and non-pathogenic microbes? One hypothesis is that host cells do so by monitoring their cytosol for microbial products. To identify bacterial products that stimulate host cytosolic surveillance pathways, we screened for Listeria monocytogenes mutants that caused enhanced or diminished host cell responses. We screened for two distinct responses; induction of type 1 interferon and for inflammasome activation. Most of the mutants that led to altered IFN responses mapped to genes encoding multidrug efflux pumps or their cognate receptors. These data were consistent with a model in which a small molecule is either actively or inadvertently being pumped from cells, and that the host can recognize and respond. Using conventional biochemistry and mass spectrometry, we identified the L. monocytogenes molecule as cyclic-di-AMP and identified the di-adenylate cyclase (DacA) and showed that it was essential and a c-di-AMP phosphodiesterase (Pde) which was not essential. Thus, c-di-AMP represents an essential and conserved bacterial signaling molecule and a new PAMP that activates the IRF3/Sting-dependent pathway.
Wild-type L. monocytogenes activates low levels of inflammasome activation. Most of the mutants that led to enhanced inflammasome activation were shown to undergo bacteriolysis in the host cell cytosol and activate an AIM2, DNA-dependent, pathway of inflammasome activation. We next addressed the role of inflammasome activation during infection and immunity. In summary, we found that strains engineered to activate the inflammasome were severely attenuated and were poor inducers of protective immunity.
Host: Jim Miller & Michelle Dziejman
Co-Sponsored by the HIV Training Grant and the
Developmental Center for AIDS Research (DCFAR)
James Arthos, Ph.D.
Laboratory of Immunoregulation
NIAID
Title: Mucosal Transmission of HIV and the Role of the a4b7+ Subset of CD4+ T cells
Research Interests: Role of HIV gp120 Signal Transduction in Viral Replication and Immune Dysfunction. The goal of this project is to characterize the interaction between the HIV envelope and its cellular receptors. This characterization will provide information fundamental to the basic pathogenic mechanisms that underlie HIV disease. The HIV envelope is remarkable in its ability to interact with at least three different cell surface receptors, and it is this unique property that has led us to undertake this project. Our approach involves combining biochemical characterization of envelope proteins with the responses of cells involved in immune responses to envelope treatment. We have recently developed a recombinant envelope expression system to produce and evaluate over a dozen different recombinant envelopes. These recombinants will be used to fully characterize the effects of HIV envelope proteins on the functionality of CD4+ T cells, CD8+ T cells, NK cells, dendritic cells, and B cells. HIV-1 gp120 transduces near-simultaneous signals through CD4 and a chemokine receptor (CCR5 and/or CXCR4). Recent findings involve HIV-1 envelope protein gp120 binding to an activated form of α4β7 on CD4+ T cells, NK cells, and CD8+ T cells. Understanding the complexities and significance of the signaling processes that gp120 mediates will enhance our understanding of HIV-1 pathogenesis and may facilitate the discovery of new strategies for the treatment and prevention of HIV-1 disease.
Host: Stephen Dewhurst
Co-Sponsored by the Allergy/Rheumatology Division
Associate Member
Trudeau Institute
Title: How aging impacts CD4 T cell function
Research Interest : The Impact of Aging on Immune Responses; Examination of Vaccine Efficacy and Protection from Infection
Host: Fran Lund
Associate Professor of Biochemistry
Witebsky Center for Microbial
Pathogenesis & Immunology
School of Medicine & Biomedical Sciences
State University of New York at Buffalo
Title: Pathways underlying mutagenesis and pathoadaptation in bacteria
Research Interest : Regulation and coordination of DNA replication, DNA repair and DNA damage tolerance; Mechanisms underlying clonal expansion and pathoadaptation in Pseudomonas aeruginosa
Host: Steven Gill
Professor and Chair Department of Biology
University of Rochester
Title: "Biogenesis of Bacterial Ribosomes"
Research Interest : Assembly of the E. coli 30S ribosomal subunit
Host: Martin Pavelka
Craig T. Jordan, Ph.D.
Professor of Medicine in the
Hematology/Oncology Division;
Philip and Marilyn Wehrheim Professor
University of Rochester
Title: Characterization and targeting of leukemia stem cells
Host: Fran Lund
Founder, President & Chief Executive Officer
Vaccinex, Inc.
Seminar Abstract: Semaphorin 4D (SEMA4D/CD100) signals through the Plexin-B1 receptor to regulate cell migration in multiple tissues including activation of endothelial cells for neo-vascularization and of epithelial cells to promote tumor invasion. In neuronal tissues, SEMA4D negatively regulates the survival and migration of neuronal precursors and differentiation of pre-myelinating oligodendrocytes while also promoting activation of neuroinflammatory microglia. Vaccinex is developing an antibody to SEMA4D as a therapeutic for cancer and multiple sclerosis.
Host: Brian Ward
Sponsored by the Immunology Training Grant
Professor of Biochemistry & Molecular Biology
SUNY Upstate Medical University
Research Abstract : Our philosophy is to test central hypotheses regarding the kinetic mechanism and thermodynamics of protein folding, while at the same time improving properties of existing proteins and creating novel proteins with completely new functions. To achieve this goal we employ a variety of structural, biophysical, biochemical, and molecular biological approaches including: Nuclear magnetic resonance and X-ray crystallography; Optical spectroscopy (fluorescence, circular dichroism); Thermodynamic and kinetic analysis of protein folding; Hydrogen and thiol-disulfide exchange mechanisms' Protein functional assays
Host: Minsoo Kim
Associate Professor of Virology
Cornell University College of Veterinary Medicine,
Baker Institute for Animal Health
Research Interest : Study of Feline Caliciviruses and Mammalian Orthoreoviruses
Research Abstract: Research in the Parker lab focuses on two aspects of reovirus biology. Firstly, the role of reovirus factories in assembly of new virions, where they seek to define mechanism(s) by which viral and host factors are recruited to viral “factories” (VFs) – the cytoplasmic sites of reovirus replication and assembly, and also study how those factors interact to promote the efficient assembly of new viral particles. A second project concerns the role of the reovirus outer capsid protein μ1 in apoptosis induction. Reoviruses are currently in phase I/II clinical trials as viral oncolytic agents, and the Parker laboratory has shown that μ1 is the primary determinant of apoptosis induction. Current work focuses on the role of μ1 in viral pathogenesis and the regulation of virus-induced apoptosis. In a third, unrelated project, Dr. Parker’s lab studies the capsid structure, receptor-interactions and receptor-mediated virus entry of feline calicivirus. The functional receptor molecule FCV is feline Junctional Adhesion Molecule A. FCV is the only member of the Caliciviridae for which a functional receptor has been identified and thus serves as a model for human norovirus receptor-interactions and entry, which cannot be studied because of the lack of a suitable in vitro tissue culture system. These studies seek to define the molecular and cellular controls of calicivirus infections by examining differences in virulence between viral strains that infect cats.
Host: Toru Takimoto
Co-Sponsored by the HIV Training Grant and the Developmental Center for AIDS Research (DCFAR)
Head - Virus-Cell Interaction Section,
HIV Drug Resistance Program
NCI
Title: HIV Assembly, Release, and Maturation
Seminar Abstract : The overall goal of the Virus-Cell Interaction Section is to understand basic mechanisms of retroviral replication at the molecular level, with an emphasis on the late stages of the HIV-1 replication cycle. Specifically, much of our current effort is aimed at understanding HIV-1 Gag trafficking, Env incorporation, virus assembly, budding, release, and maturation. We have a special interest in the complex relationship between viral proteins and cellular factors and pathways. We believe that the elucidation of fundamental aspects of the retrovirus replication cycle will suggest novel targets for the development of antiretroviral therapies.
Host: Luis Martinez-Sobrido
Co-Sponsored by the Pathogenesis Training Grant
Associate Professor of Microbiology & Immunology
Dartmouth Medical School
Title: Molecular interactions between Candida albicans and Pseudomonas aeruginosa and their relevance in disease
Research Interests: Bacterial-fungal interactions; Pseudomonas aeruginosa virulence; Candida albicans signaling
Host: Melanie Wellington
Co-Sponsored by the Pathogenesis Training Grant
Assistant Professor of Microbiology
Biological Sciences Division,
University of Chicago
Title: "Home remodeling : hepatitis C and dengue virus-host interactions"
Seminar Abstract: As simple genetic viruses, hepatitis C virus and dengue virus depend extensively on the host cell for their replication. We have identified ~75 host cofactors of viral replication using RNA interference analysis. This data was combined with the development of live cell imaging approaches to visualize viral infection at the single cell level in real time. A dynamic, single particle analysis of HCV entry and release pathways will be presented. Additionally, diverse mechanisms by which HCV and dengue virus physically and metabolically remodel the host cell to create an optimal environment for replication will be proposed.
Host: Joshua Munger
Co-Sponsored by the HIV Training Grant and the Developmental Center for AIDS Research (DCFAR)
Assistant Professor of Medicine
Pulmonary and Critical Care Unit
Massachusetts General Hospital,
Harvard Medical School
Research Interests: Role of Leukotriene B4 in Inflammatory and Immune Responses; Mechanisms of Fibroblast Migration and Recruitment in Pulmonary Fibrosis; Regulation of Cytolytic T Cell (CTL) Trafficking in HIV Infection; Lymphocyte Trafficking in Cerebral Malaria
Host: Stephen Dewhurst
Microbiology Graduate Student Hosted Seminar
Associate Professor of Microbiology
School of Molecular and Cellular Biology
University of Illinois at Urbana-Champaign
Research Interests: Host-Pathogen Interactions, Signal Transduction, Toxins
Host: Kelly Miller
Co-Sponsored by the Pathogenesis Training Grant
Stacey L. Schultz-Cherry, Ph.D.
Associate Member of St. Jude Faculty
Department of Infectious Diseases
St. Jude Children's Research Hospital
Title: Pathogenesis of RNA Viruses : Influenza and Astroviruses
Research Abstract: The goal of this seminar is to present our recent data on influenza virus and astrovirus pathogenesis. Outbreaks of influenza continue to cause morbidity and mortality worldwide. Epidemiological data during the 2009 pandemic suggested for the first time that obesity is a risk factor for developing severe influenza virus infection. Our studies in obese animals confirm this and provide a mechanistic explanation for the finding. Astroviruses are a leading cause of childhood gastroenteritis. We developed the only small animal model for astrovirus infection and demonstrate that the viral capsid protein is a unique enterotoxin that increases intestinal permeability by disrupting tight junctions. We’ll discuss the mechanism(s) underlying this finding.
Host: Toru Takimoto
Co-Sponsored by the Pathogenesis Training Grant
James B. Duke Professor and Chair;
Director - Center for Microbial Pathogenesis
Duke University Medical Center
Title: "Sexual reproduction and evolution of eukaryotic microbial pathogens"
Seminar Abstract: How microbial pathogens evolve, develop drug resistance, and interact with the host involves both genetic change and exchange. In bacteria, genetic exchange occurs largely via horizontal gene transfer whereas in fungi genetic exchange is driven by sexual reproduction. We focus on how sexual identity is defined and the modes and roles of sexual reproduction in virulence, production of infectious propagules, and the generation of diversity. Many fungi once thought to be asexual have been revealed by genomics to retain the machinery for sex, and laboratory studies are uncovering extant sexual cycles that enable but limit genetic exchange, generating populations with clonal features. Studies on the pathogens Cryptococcus neoformans and Cryptococcus gattii have defined the structure and evolution of an unusually large, complex mating type locus with links to sexual identity and virulence, shown that sex occurs in environmental niches (pigeon guano, plants), documented that spores produced by sex serve as infectious propagules, and revealed an unusual type of sex involving only one mating type (same-sex mating) that generates infectious spores and diversity within unisexual populations. Studies on closely aligned saprobic species (Cryptococcus amylolentus and Cryptococcus heveanensis) reveal extant tetrapolar sexual cycles, and support the proposed evolutionary model for the transition from tetrapolar to bipolar sex determination in the pathogenic species complex. Studies on the Candida pathogenic species complex illustrate plasticity in the mating type locus, in the modes of parasexual/sexual reproduction involving partners of opposite or the same mating type, and in the parameiotic/meiotic machinery leading to generation of recombinant progeny with frequent aneuploidy. Studies on the mating type locus and sexual reproduction of the dimorphic fungal pathogens and the dermatophytes contribute both experimental advances and provide examples in which mating may occur on the host. And studies of the sex locus of model and pathogenic zygomycete fungi (Phycomyces, Mucor, Rhizopus) reveal divergent HMG domain proteins govern sexual identity, with implications for how sex and sex determination evolve, and a novel example of size dimorphism linked to virulence. Taken together, these studies of sexual reproduction and its evolution and impact throughout the fungal kingdom illustrate general principles by which genetic diversity is generated and maintained in microbial pathogens, with implications for both other pathogens and multicellular eukaryotes.
Host: Damian Krysan
Sponsored by the Immunology Training Grant
Sealy and Smith Professor of Pediatrics
Vice Chair for Research
Director
Division of Clinical and Experimental Immunology & Infectious Diseases (CEIID)
Department of Pediatrics
University of Texas Medical Branch at Galveston
Research Interest: The Macrophage Inflammatory Protein (MIP-1a) is a chemokine produced by viral infected lungs. MIP-1a has potent activities on natural killer (NK) cells and cytotoxic T lymphocytes (CTL) that may function as a bridge between innate and adaptive immune responses to RSV infection.
Host: Paige Lawrence
Co-sponsored by the DCFAR (Developmental Center for AIDS Research)
Professor of Pathology
University of Utah
Research Interest: HIV-1 VPR in lymphocytes and macrophages
Research Abstract: HIV-1 encodes four accessory proteins, Vif, Vpr, Vpu and Nef. These are small proteins with multiple functions, and regulate various aspects of the virus-host cell relationship. My laboratory has primarily focused on Vpr. Vpr induces cell cycle arrest in the G2 phase. The immediate consequence of this activity of Vpr is that infected cells do not enter mitosis and, therefore, do not divide. A later consequence of the cell cycle disturbance is that the infected cell commits to apoptosis or programmed cell death. We hypothesize that this chain of events explains, at least in part, the severe depletion in CD4-positive lymphocytes observed during the acquired immunodeficiency syndrome.
A major research objective of my laboratory is to understand, at a molecular level, the succession of signaling events that ultimately lead to the induction of apoptosis. We have found that Vpr interferes with the normal DNA replication of dividing cells. This interference, in turn activates a cellular system that monitors the integrity of DNA as well as the processivity of DNA replication. This system is known as the ATR serine-threonine kinase.
Through activation of the ATR kinase, Vpr accomplishes the activation of two different, but interdependent signaling cascades, leading to cell cycle disruption and apoptosis.
Host: Stephen Dewhurst
Virology Student Hosted Seminar
Professor of Medicine and
Microbiology & Immunology
Director - Institute of Human Virology
University of Maryland
Research Interest: Dr. Gallo’s research interests currently focus on the development of an effective HIV preventive vaccine and the development of innovative HIV therapies.
Personal History :Robert C. Gallo, M.D., became world famous in 1984 when the U.S. government announced that he had co-discovered the human immunodeficiency virus (HIV) to be the cause of AIDS. Little was known then of the mysterious illness that was fast becoming the deadliest epidemic in medical history. Dr. Gallo has spent the past two decades trying to solve one of humanity’s greatest scientific challenges.
Though best known for his co-discovery of HIV, Gallo and his team in the early 1980s also pioneered the development of the HIV blood test, which enabled health care workers for the first time to screen for the AIDS virus - leading to a more rapid diagnosis while simultaneously protecting patients receiving blood transfusions. His research also helped physicians develop HIV therapies to prolong the lives of those infected with the virus. His discovery in 1996 that a natural compound known as chemokines can block the HIV virus and halt the progression of AIDS was hailed by Science magazine as one of that year's most important scientific breakthroughs.
Before the AIDS epidemic, Gallo was the first to identify a human retrovirus and the only known human leukemia virus - HTLV - one of few known viruses shown to cause a human cancer. In 1976, he and his colleagues discovered Interleukin-2, which is a growth-regulating substance now used as therapy in some cancers and sometimes AIDS. And in 1986, he and his group discovered the first new human herpes virus in more than 25 years (HHV-6), which was later shown to cause an infantile disease known as Roseola.
Today, Dr. Gallo's work continues at the Institute of Human Virology (IHV), an institute of the University of Maryland School of Medicine that Dr. Gallo helped found in 1996. IHV is a first-of-its-kind virology center that combines the disciplines of research, patient care and prevention programs in a concerted effort to speed the pace of progress.
Prior to becoming IHV director in 1996, Gallo spent 30 years at the National Institutes of Health's National Cancer Institute, where he was head of its Laboratory of Tumor Cell Biology. A Connecticut native, his interest in science and medicine was first stirred by the loss of his 6-year-old sister to leukemia when he was 13 years old. The physicians who cared for her made a lasting impression and helped Gallo decide to make scientific research - and the opportunity to help put an end to deadly diseases - his life's work.
Host: Kristy Bialas
Warner-Lambert Parke-Davis
Professor of Molecular Biology
Princeton University
Research Interest: Protein targeting and signal transduction; Outer membrane biogenesis
Host: Martin Pavelka
Professor, Immunology
Adjunct Professor, Microbiology &
Global Health Affiliate Investigator
Clinical Research Division, Fred Hutchinson Cancer Research Center, Department of Immunology, University of Washington
Research Interest: Research in the Gale laboratory is focused on understanding innate immunity to virus infection, and the intracellular immune processes and virus-host interactions that govern viral replication and infection outcome. The laboratory is a component of the Hepatitis C virus Cooperative Research Centers supported by the NIH. Additionally, the Gale laboratory has research programs focused on understanding immune control of West Nile virus infection, HIV infection, and the immunomodulatory/antiviral actions of interferons and small molecule inhibitors of virus replication.
Host: Luis Martinez-Sobrido
Professor of Microbiology and Immunology
Harvard Medical School
Title: "Exploring Bacterial Communication Through Chemical Ecology"
Seminar Abstract: Chemical signaling is basic to all of life, shaping how organisms develop, thrive, and interact with other living systems. Bacteria are ideal for studying such chemical communication systems, since they are both easy to manipulate genetically and prolific producers of compounds. I will focus the presentation on studies of intraspecies and interspecies signaling events that affect the outcome of microbial differentiation.
Host: Steven Gill
Annual Melville A. Hare Memorial Lecture -
Hosted by Immunology Students
Professor of Pathology & Co-Director
Mouse Pathology Core
Co-Leader
Cancer, Immunity, and Microenvironment Program Pathology and Cancer Research Institute
University of California - San Francisco
Research and Clinical Interests: Inflammation, Proteolysis, Tissue Remodeling and Cancer Development
Student Contact: Sesquile Ramon
Professor of Microbiology & Immunology
and of Orthopaedics
University of Arkansas for Medical Sciences
Research Interest: Molecular Pathogenesis of Staphylococcus aureus infections
Host: Paul Dunman
Professor and Director of RNA Biology
Research Interests: RNA Rregulation of Development and Disease
Host: Sanjay Maggirwar
This listing includes selected seminars sponsored by other Departments/Centers which may be of interest to Microbiology students and faculty. Seminars hosted by the Department of Microbiology and Immunology are supported in part by a generous donation from Lederle-Praxis Biologicals, as well as by the indicated additional sources.
Events Calendar
To view upcoming events on the URMC Scientific Events Calendar, please click here.
