This proposal describes a five year, twopart career development program in the study of Mycobacterium tuberculosis. This program will be carried out in the laboratory of Dr. Barry Bloom with the additional guidance of Dr. Eric Rubin, both in the Division of Immunology and Infectious Diseases at the Harvard School of Public Health. The candidate is trained in Infectious Diseases and has the long term goal of establishing an independent laboratory studying M. tuberculosis pathogenesis with a particular focus on mycobacterial interaction with the host immune response and vaccine development. The didactic component of this program involves courses in molecular biology and immunology through Harvard University. The research component of this program involves exploration of two putative mechanisms of immune evasion by M. tuberculosis, inhibition of IFN-gamma signaling and inhibition of inducible IL-12 production in infected macrophages.
The specific aims of the research proposed will be: 1) to determine whether Toll-like receptor 2 (TLR-2) activation inhibits IFN-gamma signaling or inducible IL-12 production; 2) to identify the M. tuberculosis genes required for inhibition of IFN-gamma and IL-12 signaling by screening a transposon mutagenized library of M. tuberculosis; and 3) to characterize the genes identified in these screens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI050734-04
Application #
6893977
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Jacobs, Gail G
Project Start
2002-09-01
Project End
2007-05-31
Budget Start
2005-06-01
Budget End
2007-05-31
Support Year
4
Fiscal Year
2005
Total Cost
$122,315
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Fortune, Sarah M; Chase, Michael R; Rubin, Eric J (2006) Dividing oceans into pools: strategies for the global analysis of bacterial genes. Microbes Infect 8:1631-6
Fortune, S M; Jaeger, A; Sarracino, D A et al. (2005) Mutually dependent secretion of proteins required for mycobacterial virulence. Proc Natl Acad Sci U S A 102:10676-81
Fortune, Sarah M; Solache, Alejandra; Jaeger, Alejandra et al. (2004) Mycobacterium tuberculosis inhibits macrophage responses to IFN-gamma through myeloid differentiation factor 88-dependent and -independent mechanisms. J Immunol 172:6272-80