News Release

42 biomedical scientists worldwide named HHMI international research scholars

Grant and Award Announcement

Howard Hughes Medical Institute

Tuberculosis, malaria, hemorrhagic fevers, and anthrax all are infectious and parasitic diseases posing a global problem that calls for a global solution. So the Howard Hughes Medical Institute (HHMI) is awarding $17.5 million to 42 outstanding scientists in 20 countries to tackle the mysteries of the molecular and genetic mechanisms underlying infectious and parasitic disease. What they learn could help identify potential new drug targets and develop vaccines.

Nearly 500 scientists from 62 countries applied for the five-year awards. HHMI selected researchers from Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, Hungary, India, Israel, Mali, Mexico, Portugal, Russia, South Africa, Spain, Switzerland, Thailand, and Uruguay. Each will receive $350,000 to $500,000 U.S. dollars over five years.

"Through its international program, HHMI is supporting scientists of the highest quality in their home countries," said Institute President Thomas R. Cech, a Nobel prize-winning chemist. "We also bring these international scholars together with each other and with other scientists in the HHMI community to create an international network of scientific excellence."

Since HHMI awarded its first infectious diseases and parasitology grants in 2000, more than 50 transnational collaborations have sprung from annual science meetings where the international research scholars gather to present their research and learn what their colleagues from around the world are doing.

"HHMI's international program underscores a growing recognition of the international scope of science and of the way international cooperation invigorates research," said Peter J. Bruns, HHMI vice president for grants and special programs. "HHMI's support of these scientific leaders in their home countries encourages the most creative researchers, strengthens their research environments, and provides vital educational opportunities for upcoming scientists. Networking these scientists with each other and with our domestic investigators yields further unique opportunities for innovation."

For example:

  • Rajesh Gokhale is a talented young scientist who, despite attractive job offers in the United States, chose to return to his native India to study the unique mechanisms used by Mycobacterium tuberculosis, which causes TB, to modulate the proteins and lipids of its cell walls in response to changes in its environment. Understanding this "enzymatic crosstalk" in M. tuberculosis could help explain the subtle ways that the pathogen generates different reactions under varying circumstances.
  • Valerie Mizrahi of the University of the Witwatersrand in Johannesburg, South Africa, a recognized leader in tuberculosis research, recently was named co-director of the only medical Centre of Excellence established by the South African Department of Science and Technology. Mizrahi studies the mechanisms underlying TB's remarkable ability to adapt to adverse conditions and persist in a dormant state from which it can reactivate to cause disease. She also devotes considerable effort to mentoring young South African scientists. This is her second HHMI infectious diseases and parasitology research award.
  • Sumalee Kamchonwongpaisan from Bangkok, Thailand, will investigate how artemisinin, an effective antimalarial drug, clears parasites from infected red blood cells. Understanding the precise mechanisms of artemisinin action could lead to new targets for better drugs for treating malaria. Kamchonwongpaisan already is collaborating with two other HHMI international research scholars, Alan Cowman and Brendan Crabb, who do malaria research at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.

    Half of the new awardees are first-time HHMI grant recipients. The other 21 are current HHMI international research scholars.

    The Institute also supports the work of outstanding scientists in the Baltics, Central and Eastern Europe, Russia and Ukraine and of another group from Latin America and Canada. Competitions are currently under way for grants in both programs.

    2005 HHMI International Research Scholars in Infectious Diseases and Parasitology

    Alex Andrianopoulos, Ph.D.
    Associate Professor of Genetics
    University of Melbourne
    Melbourne, Australia
    Alex Andrianopoulos will research the human pathogen Penicillium marneffei, a fungus that can grow in either a unicellular or multicellular form, depending on the temperature surrounding it. Andrianopoulos will attempt to identify genes controlling this change in form at the molecular and cellular level. His findings will have both medical and scientific value, as well as important implications for biotechnology.

    Michele Marie Barry, Ph.D.
    Associate Professor of Medical Microbiology and Immunology
    University of Alberta
    Edmonton, Canada
    Michele Barry will study the proteins that interfere with cell death, focusing on the mechanisms human cells use to expel viruses and the ways that viruses fight back in the vaccinia virus. Her research could provide clues for the development of new therapeutic approaches for human diseases.

    Gabrielle T. Belz, Ph.D.
    Investigator
    The Walter and Eliza Hall Institute of Medical Research
    Melbourne, Australia
    Gabrielle T. Belz will investigate the processes that induce the body to produce elevated numbers of CD8+ memory cells, which are key to the function of the human immune system. This study could have significant impact on how vaccines are developed in the future.

    * Charles Boone, Ph.D.
    Professor
    Banting and Best Department of Medical Research
    University of Toronto
    Toronto, Canada
    Charles Boone will study the genes responsible for causing vegetative, yeast-like fungi to grow in a filamentous form, which can augment the fungus's virulence. A detailed understanding of the genes controlling these processes will provide new insights into fungal pathogenicity and should identify targets for the development of novel antifungal drugs. Boone plans to disseminate his findings to the research community through an open database.

    Jean-Laurent Casanova, M.D., Ph.D.
    Professor of Pediatrics
    Pediatric Immunology Unit
    Director
    Laboratory of Human Genetics of Infectious Diseases
    Necker Medical School and Hospital for Sick Children
    University of Paris René Descartes
    Director
    Inserm Unit 550
    Paris, France
    Jean-Laurent Casanova will conduct research on the potentially fatal condition known as herpes simplex encephalitis, which, for an unknown reason, develops from herpes simplex virus-1 (HSV-1) in a small percentage of infected children. His search for a candidate gene and an understanding of the underlying immunodeficiency of this disease in families may have important medical and biological implications.

    * Pascale Françoise Cossart, Ph.D.
    Professor and Head
    Unité des Interactions Bactéries-Cellules
    Institut Pasteur
    Director
    Inserm Unit 604
    Paris, France
    Pascale Cossart will study the infection by Listeria monocytogenes, a bacterium that is one of the best models of intracellular parasitism. She will characterize the processes by which Listeria infect cells, tissues and organs and succeed in breaching host barriers.

    * Alan F. Cowman, Ph.D.
    Researcher, Division of Infection and Immunity
    The Walter and Eliza Hall Institute of Medical Research
    Melbourne, Australia
    Alan Cowman wants to know how Plasmodium falciparum, which causes the most lethal form of human malaria, invades mature red blood cells. This information will be important in determining the potential of the proteins involved in the process as vaccine and drug candidates.

    * Brendan Crabb, Ph.D.
    Chief of Laboratory
    The Walter and Eliza Hall Institute of Medical Research
    Melbourne, Australia
    Brendan Crabb will study merozoite surface proteins, the prime targets of immune responses and the leading vaccine candidates for control of the deadly human malaria parasite Plasmodium falciparum. Specifically his group will use genetic technologies to study the relative importance of specific merozoite antigens.

    Christoph Georg Fritz Dehio, Ph.D.
    Associate Professor of Microbiology
    Researcher, the Biozentrum
    University of Basel
    Basel, Switzerland
    Christoph Dehio is conducting research on bacterial pathogens associated with the formation of tumors in humans. In particular, Dehio will study the bacterium Bartonella henselae to determine the factors that lead to the formation of a vascular tumor.

    Abdoulaye Djimde, Ph.D.
    Chief of Drug Resistance Laboratory,
    Malaria Research and Training Center
    University of Bamako
    Bamako, Mali
    Abdoulaye Djimde will conduct clinical, entomological, and molecular studies to improve understanding of resistance to current inexpensive and commonly prescribed antimalarial drugs. He will focus on improving the understanding of the mechanisms involved in the spread of Plasmodium falciparum resistance to quinine and sulfadoxine-pyrimethamine.

    Jean Dubuisson, D.V.M., Ph.D.
    Chief of Laboratory at Centre National de la Recherche Scientifique" (CNRS)
    Institute of Biology of Lille
    Institut Pasteur of Lille
    Lille, France
    Jean Dubuisson will study the hepatitis C virus (HCV), a major cause of chronic liver disease worldwide. Basic knowledge of the HCV life cycle is needed to better combat the deadly pathogen. Dubuisson is analyzing this life cycle during multiple stages of HCV development, which may speed the development of improved antiviral drugs targeting HCV entry.

    * B. Brett Finlay, Ph.D.
    Peter Wall Distinguished Professor
    University of British Columbia
    Vancouver, Canada
    B. Brett Finlay is studying the pathogenic strains of E. coli bacteria, which account for significant illness and death worldwide. He will investigate the specific mechanisms by which E. coli attaches to and interacts with host cells. Specifically, Finlay hopes to determine which E. coli genes are associated with pathogenicity, how E. coli interacts with host cells at the molecular level, and how E. coli disease mechanisms relate to animal colonization, shedding, and disease.

    * Simon James Foote, M.B.B.S., Ph.D.
    Director
    The Menzies Research Institute
    Research Professor
    The Walter and Eliza Hall Institute of Medical Research
    Hobart, Australia (Menzies)
    Melbourne, Australia (WEHI)
    Simon Foote is attempting to understand how the host defends itself against malaria resistance by infecting genetically similar mice carrying rare mutations with malaria and studying the mutations that allow animals to survive infection. This research should help scientists gain insight into host response to malaria, as well as develop new, more effective anti-malarial therapies.

    Andrea Vanesa Gamarnik, Ph.D.
    Head of Laboratory
    Fundación Instituto Leloir
    Buenos Aires, Argentina
    Andrea Gamarnik will study the molecular mechanisms of dengue virus replication. It is estimated that more than 50 million human dengue virus infections occur annually in the tropical and subtropical regions of the world. Currently, neither vaccines nor antiviral drugs exist to control dengue infections. Her work will facilitate identification of novel antiviral strategies against dengue virus.

    Rajesh S. Gokhale, Ph.D.
    Staff Scientist
    National Institute of Immunology
    New Delhi, India
    Rajesh S. Gokhale will investigate how molecular repertoire in nature is generated from a limited number of genes. His study of "enzymatic crosstalk" in M. tuberculosis will provide insight into mechanisms employed by pathogens to generate metabolite diversity.

    * H. Ulrich Göringer, Ph.D.
    Professor of Microbiology and Genetics
    Darmstadt Technical University
    Darmstadt, Germany
    Hans Goringer is working to develop tools that will be useful in identifying new drugs to combat trypanosome infections, caused by parasitic flagellate protozoa and widespread in the developing world. He will focus on drugs capable of crossing the blood-brain barrier.

    Emanuel Hanski, Ph.D.
    Professor of Clinical Microbiology
    Institute of Microbiology
    Hebrew University, Faculty of Medicine
    Jerusalem, Israel
    Emanuel Hanski will study invasive strains of group A streptococcus, bacteria that causes necrotizing fasciitis, also known as the flesh-eating disease. He will focus on the identification of factors related to bacterial virulence and their mode of regulation. Identification of these factors and learning how virulence is regulated may lead to better prevention and treatment of this life-threatening disease in humans.

    * William Ross Heath, Ph.D.
    Chief of Laboratory
    The Walter and Eliza Hall Institute of Medical Research
    Melbourne, Australia
    William Heath will investigate the effects of the interaction between malarial parasites and dendritic cells, which initiate immunity, on the disease's ability to overcome the efforts of a competent immune system. Heath will study which specific types of dendritic cells capture malaria and how these important immune cells are affected by a full-fledged infection by Plasmodium. His research could lay the groundwork for development of new and more effective treatments for human malarial infections.

    Anja Tatiana Ramstedt Jensen, Ph.D.
    Associate Professor
    Institute of Medical Microbiology and Immunology
    Faculty of Health Sciences
    University of Copenhagen
    Copenhagen, Denmark
    Anja T.R. Jensen will study molecular differences between malaria parasites causing severe and non-severe malaria in children. Antibody reactivity to the identified molecules will be analyzed in individuals showing different malaria symptoms and living in malaria endemic areas. Her work should help identify antigens for a malaria vaccine.

    Sumalee Kamchonwongpaisan, Ph.D.
    Researcher
    National Center for Genetic Engineering and Biotechnology
    National Science and Technology Development Agency
    Thailand Science Park
    Pathumthani, Thailand
    Sumalee Kamchonwongpaisan works on potential molecular targets of antimalarial drugs, with focus on derivatives of artemisinin, one of the most effective antimalarial drugs, and on antifolate drugs that interfere with synthesis of DNA and other essential components of the malaria parasite. Her study will lead to a better understanding of the modes of action of antimalarials, and hopefully to the development of effective new drugs.

    Elena A. Levashina, Ph.D.
    Researcher
    Institut de Biologie Moleculaire et Cellulaire
    Laureate
    Inserm Avenir program
    Strasbourg, France
    Elena A. Levashina will study the role of the insect immune system in the survival of malaria parasites in the Anopheles mosquito, the insect vector that transmits malaria to humans. Her work has implications for development of novel vector control strategies.

    Yuesheng Li, M.D., Ph.D.
    Chief of Laboratory
    Hunan Institute of Parasitic Diseases
    Yueyang, China
    Yuesheng Li's research consists of two linked projects designed to improve understanding of the immunobiology of infection and the pathology of schistosomiasis, a parasitic disease that is widespread in rural areas of Africa, Asia, and Latin America. One component will focus on susceptibility for infection. The other will investigate possible genetic control of susceptibility to advanced disease.

    * Susana Lopez, Ph.D.
    Professor of Genetics and Molecular Biology
    Institute of Biotechnology
    National Autonomous University of Mexico
    Cuernavaca, Mexico
    Susana Lopez will study several aspects of rotavirus-host cell interaction, including the virus's mechanism of entry into cells, transcription and replication of the viral genome, and the mechanism the virus uses to take over the cell's translation machinery. Rotaviruses are the most important cause of severe diarrhea in young children worldwide.

    * Hugo D. Lujan, Ph.D.
    Adjunct Professor
    Department of Biological Chemistry
    School of Medicine National University of Córdoba
    Scientist
    Mercedes and Martín Ferreyra Institute for Medical Research, CONICET
    Córdoba, Argentina
    Hugo D. Lujan studies Giardia, a parasitic protozoa that is a major source of water-borne diarrheal disease. His goal is to better understand the basic molecular mechanisms involved in intracellular protein trafficking and antigenic variation in Giardia, which enables the parasite to evade its host's immune responses.

    Vilma Regina Martins
    Researcher
    Ludwig Institute for Cancer Research
    Sao Paulo, Brazil
    Vilma Martins is studying the physiological mechanisms underlying cellular prion proteins' loss of function and their roles in prion disease. Prions are microscopic protein particles that are thought to cause certain neurodegenerative diseases, such as so-called mad cow disease. She will work with a group to establish systematic human prion disease screening in Brazil.

    * Geoff McFadden
    Professor
    School of Botany
    University of Melbourne
    Melbourne, Australia
    Geoff McFadden's work will focus on a tiny, vital organelle within the malaria parasite called an apicoplast. His goal is to understand how drugs that disrupt the apicoplast work and how the apicoplast is powered. The information gained could assist in malaria drug development.

    Grant McFadden
    Scientist
    Robarts Research Institute
    Professor
    University of Western Ontario
    London, Canada
    Grant McFadden will investigate the cellular components of two anti-viral pathways that his research team uncovered during earlier studies of poxvirus infection in mammalian cells. He hopes the studies will better define the molecular mechanisms that control the host-virus species barrier and provide insights into host pathways that viruses must circumvent when invading a new host species.

    * Robert Menard
    Chief of Laboratory
    Institut Pasteur
    Paris, France
    Robert Menard studies Plasmodium, the genus of parasites that cause malaria. He plans to identify and characterize the proteins produced by Plasmodium in two of its early stages, before it infects red blood cells and causes symptoms of malaria. What he learns may be useful in developing protection strategies against the early stages of malaria infection.

    * Shulamit Michaeli
    Professor
    Faculty of Life Sciences
    Bar-Ilan University
    Ramat-Gan, Israel
    Shulamit Michaeli will examine the regulation of gene expression at the RNA level in parasitic trypanosomes. These organisms are an excellent model for studying RNA processing mechanisms because they regulate their genes mainly at the post-transcriptional level and harbor unique mechanisms such as trans-splicing and editing. Better understanding of the complex RNA world of these parasites, which cause diseases such as Chagas and sleeping sickness, may lead to development of RNA-based therapies.

    * Valerie Mizrahi
    Professor
    School of Pathology
    University of the Witwatersrand, Johannesburg
    Alternate-Director
    DST-NRF Centre of Excellence for Biomedical TB Research
    Johannesburg, South Africa
    Valerie Mizrahi plans to study the mechanisms of DNA metabolism, culturability, and resuscitation in Mycobacteria tuberculosis, the organism that causes human tuberculosis. Development of more effective tools for TB control requires understanding the mechanisms underlying TB’s remarkable ability to adapt to adverse conditions and persist in a dormant state from which it can reactivate to cause disease.

    Maria Manuel Mota
    Group Leader
    Instituto de Medicina Molecular
    Faculty of Medicine
    University of Lisbon
    Lisbon, Portugal
    Maria Mota hopes to determine the host molecules and mechanisms required for development of the malaria parasite Plasmodium inside the liver cells of its host. She plans to apply a systematic RNA interference (RNAi) screen to determine which molecules are required for successful parasite development.

    * Laszlo Nagy
    Associate Professor
    Department of Biochemistry and Molecular Biology
    University of Debrecen Medical and Health Sciences Center
    Debrecen, Hungary
    Laszlo Nagy will use pharmacological and genetic approaches to delineate the pathways regulated by PPARg, a transcription factor that plays a key lipid-handling role in macrophages, immune-system cells that control inflammation. He plans to use targeted elimination of PPARg from mouse macrophages to determine its effect on infectious disease models.

    Miguel Navarro
    Chief of Laboratory
    Instituto de Parasitologia y Biomedicina Lopez-Neyra
    Consejo Superior de Investigaciones Cientificas
    Granada, Spain
    Miguel Navarro will examine the way parasites like Trypanosoma brucei, which causes African sleeping sickness, elude the host's immune response by changing their protein coatings. His research will use molecular and cell biology tools including nuclear architectural positional analysis, proteomics, and functional complementation of promoter activity.

    * Sergei A. Nedospasov
    Professor and Head
    Laboratory of Molecular Immunology
    Engelhardt Institute of Molecular Biology
    Russian Academy of Sciences and
    A.N. Belozersky Institute of Physico-Chemical Biology
    Moscow State University
    Moscow, Russia
    Sergei Nedospasov plans to use a mouse model to study the effects of a continuous blockade of TNF (tumor necrosis factor), a key factor in innate immunity. Similar blockades occur in arthritis. He hopes to define the parameters of the weakening of the host's defense, which could be useful in developing more effective therapeutic strategies.

    * Rafael Radi
    Professor of Biochemistry
    Facultad de Medicina, Universidad de la República
    Montevideo, Uruguay
    Rafael Radi will test the hypothesis that during mammalian infection with Trypanosoma cruzi, the parasite that causes Chagas disease, the interplay between the metabolism of the amino acid L-arginine and oxidation-reduction processes of both the parasite and host target cells determine cell survival or death. He will test the hypothesis using biochemical, cellular, and in vivo model systems. The finding may permit development of novel and effective infection control strategies.

    Isabel Roditi, D.Habil, Ph.D.
    Director
    University of Bern
    Bern, Switzerland
    Isabel Roditi wants to learn more about surface proteins that govern survival and transmission of Trypanosoma brucei, the parasite that causes sleeping sickness, by its insect host, the tsetse fly. Using a fully transmissible strain of T. brucei will enable her to monitor the parasite throughout its life cycle in the fly. The long-range goal of such studies is to find ways to interrupt transmission of the disease.

    * Philippe J. Sansonetti
    Professor and Head
    Unité de Pathogénie Microbienne Moléculaire
    Institut Pasteur
    Director
    Inserm Unit 389
    Paris, France
    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 plans to analyse the mechanisms of immunity against Shigella, hoping to use his findings to develop vaccine candidates.

    * D. Louis Schofield
    Chief
    Laboratory of Malaria Immunology
    The Walter and Eliza Hall Institute of Medical Research
    Melbourne, Australia
    Louis Schofield will investigate the role of innate immunity and the parasite toxin in susceptibility and resistance to severe malaria. He hopes that determining the role of the toxin and innate responses in disease and the role of anti-toxin antibodies and counter-regulatory mechanisms in clinical immunity to malaria will provide a rational basis for the development of interventions that prevent malaria fatalities.

    * Dominique Soldati-Favre
    Associate Professor
    Department of Microbiology and Molecular Medicine
    University of Geneva
    Geneva, Switzerland
    Dominique Soldati-Favre wants to identify and characterize the proteases that enable a family of parasitic protozoa called Apicomplexa to attach themselves to and actively invade host cells. Proteases are enzymes that break down proteins into peptides and amino acids. The parasite Toxoplasma gondii, which causes toxoplasmosis, will be used to do functional, biochemical and structural analyses of candidate proteases. Validation of the proteases as potential drug targets will be conducted in Plasmodium falciparum, the malaria parasite.

    * Natalie C.J. Strynadka
    Associate Professor
    Department of Biochemistry and Molecular Biology
    University of British Columbia
    Vancouver, Canada
    Natalie Strynadka will use X-ray crystallography and other biophysical analysis tools to study the structure and function of proteins that play key roles in antibiotic resistance and bacterial pathogenicity. The goal is design of novel antibiotics.

    Santuza M.R. Teixeira
    Associate Professor
    Department of Biochemistry and Immunology
    Federal University of Minas Gerais
    Minas Gerais, Brazil
    Santuza Teixeira studies genomic variability in Trypanasoma cruzi, the parasite that causes Chagas disease. She plans to analyze DNA sequences of several gene families that encode antigens or surface molecules of T. cruzi. She also will look at differences in gene expression and in the activity of DNA repair machinery in the parasite.

    Gisou F. van der Goot
    Associate Professor
    University of Geneva
    Geneva, Switzerland
    Gisou van der Goot wants to understand the mechanisms by which anthrax toxin manages to delay the onset of normal immune responses. She will use a variety of cell biological, morphological and biochemical techniques, including an RNAi screen, to analyze the molecular mechanisms that govern the delivery and presentation of the toxin and its enzymes in the cell.

    ###

    * Previous HHMI international research scholars


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