Systems Biology for Molecular Analysis of Tuberculosis in Ethiopia

Summary

Principal Investigator: Gobena Ameni
Abstract: Mycobacterium tuberculosis (Mtb) is estimated to have infected one third of the world's population based on reports from surveys on positive skin tuberculin tests. There are 22 high-burden countries globally, among them Ethiopia, accounting for 80% of all active tuberculosis cases. The clonal relatedness of strains circulating in humans and other potential reservoirs is poorly understood. Molecular epidemiology is gaining importance in tracking strains and addressing key public health challenges to prevent and control communicable diseases in Ethiopia, including tuberculosis (TB). Ethiopian pastoralist populations have been neglected despite their vulnerability to various infectious diseases. Surveillance of TB in these areas is also minimal. As pastoralists rely on livestock products, a significant, largely unexplored challenge is the potentially high level of transmission of tuberculosis between livestock and people. There is currently no effective vaccine protecting humans against TB. The Bacillus Calmette Guerin (BCG) vaccine consisting of attenuated Mycobacterium bovis preparations is the only approved vaccine against TB, but no longer provides protective immunity in some populations. Another challenge is the need of prolonged antibiotic treatment which, if not properly completed, accelerates the development of Mtb multi-drug resistance. Major problems in high TB disease burden countries are human and environmental factors that contribute to a weakened immune system and can increase susceptibility to Mtb infection, recurrence of latent infection and high morbidity and mortality. Modern genomics tools will considerably impact the knowledge of transmission dynamics, the extent of strain diversity and molecular interactions of TB with its host environments. In the proposed partnership between Addis Ababa University (AAU) and J. Craig Venter Institute (JCVI), the objective is to build genomics capacity at AAU, with a focus on the typing of strains of Mtb and M. bovis using Illumina Nextgen sequencing technologies and, in demonstration projects, understanding the relationships of active TB disease with host components such as the human respiratory microbiome and protein-based analysis of immune responses in the respiratory tract. This proposal includes innovative systems biology research as well as a program training Ethiopian scientists in genomics disciplines and applications to infectious diseases. 2.
Funding Period: 2013-09-20 - 2016-07-31
more information: NIH RePORT

Research Grants

  1. Population-based Approach to Malaria Research and Control
    Donald J Krogstad; Fiscal Year: 2013
  2. Molecular Analysis of Tuberculosis Immunity
    WILLIAM ROBERT JACOBS; Fiscal Year: 2013
  3. SLAM Gene Family Controlled Pathways to SLE
    CORNELIS P TERHORST; Fiscal Year: 2013
  4. Genetically-engineered pig organ transplantation into nonhuman primates
    DAVID KC COOPER; Fiscal Year: 2013
  5. INNATE IMMUNE RESPONSE TO MICROBIAL INFECTION
    William M Nauseef; Fiscal Year: 2013
  6. Transplant Tolerance in Non-Human Primates
    STUART JOHNSTON KNECHTLE; Fiscal Year: 2013
  7. Systems Analysis Vaccine Responses in Healthy and Hyporesponsive Humans
    Anna Karolina Palucka; Fiscal Year: 2013
  8. A TOLERANCE APPROACH TO XENOTRANSPLANTATION
    David H Sachs; Fiscal Year: 2013
  9. Oklahoma Center for Respiratory and Infectious Diseases
    Lin Liu; Fiscal Year: 2013
  10. Endothelial Injury and Repair: CardioPulmonary Vascular Biology COBRE
    SHARON IRENE SMITH ROUNDS; Fiscal Year: 2013

Detail Information

Research Grants30

  1. Population-based Approach to Malaria Research and Control
    Donald J Krogstad; Fiscal Year: 2013
    ..Understanding these relationships is critical to both the evaluation of current intervention effectiveness and in the translation of new tools for prevention and treatment of the disease and its transmission. ..
  2. Molecular Analysis of Tuberculosis Immunity
    WILLIAM ROBERT JACOBS; Fiscal Year: 2013
    ..smegmatis ?ike mutant containing a set of M. tuberculosis genes (named IKEPLUS) elicits a bactericidal immunity against M. tuberculosis. Heterologous prime and boosts with ILEPLUS and attenuated M. tuberculosis will be explored. ..
  3. SLAM Gene Family Controlled Pathways to SLE
    CORNELIS P TERHORST; Fiscal Year: 2013
    ..Core A Genetic Mouse Core.PL: Ninghai Wang, Beth Israel Deaconess Medical. Center Core B Administrative Core.PL Cox Terhorst, Beth Israel Deaconess Medical Center. ..
  4. Genetically-engineered pig organ transplantation into nonhuman primates
    DAVID KC COOPER; Fiscal Year: 2013
    ..abstract_text> ..
  5. INNATE IMMUNE RESPONSE TO MICROBIAL INFECTION
    William M Nauseef; Fiscal Year: 2013
    ....
  6. Transplant Tolerance in Non-Human Primates
    STUART JOHNSTON KNECHTLE; Fiscal Year: 2013
    ..This goal will be accomplished via four interrelated projects and two supporting cores. ..
  7. Systems Analysis Vaccine Responses in Healthy and Hyporesponsive Humans
    Anna Karolina Palucka; Fiscal Year: 2013
    ..abstract_text> ..
  8. A TOLERANCE APPROACH TO XENOTRANSPLANTATION
    David H Sachs; Fiscal Year: 2013
    ..abstract_text> ..
  9. Oklahoma Center for Respiratory and Infectious Diseases
    Lin Liu; Fiscal Year: 2013
    ..The completion of the goals of the present COBRE will have a major impact on research programs on respiratory infectious diseases in the State of Oklahoma. ..
  10. Endothelial Injury and Repair: CardioPulmonary Vascular Biology COBRE
    SHARON IRENE SMITH ROUNDS; Fiscal Year: 2013
    ..abstract_text> ..
  11. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  12. Southeast Regional Centers of Excellence for Biodefense &Emerging Infectious Di
    Philip Frederick Sparling; Fiscal Year: 2013
    ..SERCEB brings new investigators to the biodefense effort through a combination of educational programs, support of innovative new projects, and the synergistic interactions among its world-class investigators. ..
  13. MOLECULAR GENETIC ANALYSIS OF MYCOBACTERIUM TUBERCULOSIS
    WILLIAM ROBERT JACOBS; Fiscal Year: 2013
    ..This invaluable tool will enable the elucidationof the molecular basis for this immune evasion, part of which we have found is mediated by a large gene cluster conserved within pathogenic Mycobacterial species. ..
  14. Middle Atlantic Regional Center for Excellence for Biodefense and Emerging Infect
    MYRON MAX LEVINE; Fiscal Year: 2013
    ..abstract_text> ..
  15. Northeast Biodefense Center
    W Ian Lipkin; Fiscal Year: 2013
    ..As a Center based in a School of Public Health and a State Department of Health, the NBC has a firm commitment to and practical understanding of Emergency Preparedness. ..
  16. Molecular Analyses and Interventions for Biodefense and Emerging Pathogens
    Olaf Schneewind; Fiscal Year: 2013
    ..Research and training at the GLRCE is governed by a mechanism involving ongoing review of scientific excellence and translational goals, inter-institutional advisory boards and external scientific advisory bodies. ..
  17. TOXIC SUBSTANCES IN THE ENVIRONMENT
    Martyn T Smith; Fiscal Year: 2013
    ..The program will be overseen and coordinated by an Administration core (A). ..
  18. Pacific Southwest RCE for Biodefense &Emerging Infectious Diseases Research
    Alan G Barbour; Fiscal Year: 2013
    ..abstract_text> ..
  19. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
  20. Mucosal Immunity, Vaccines and Microbiota Interplay in Humans and Animal
    Marcelo B Sztein; Fiscal Year: 2013
    ..Given the shortcomings of available measures to successfully control this infection, and its bioterrorism potential, to develop a S. dysenteriae type 1 vaccine is of great importance. ..