Manipulation of Macrophage Responses by M. tuberculosis

Sponsor: University of California Berkeley

Location(s): United States


Tuberculosis (TB) is a persistent lung infection that has plagued mankind for centuries and ranks as one of the most serious threats to world health today.  2-3 million deaths are attributed yearly to the disease, and new urgency is added by the emergence of strains resistant to all of the available chemotherapeutic agents. The threat of drug-resistant TB as a bioterrorism agent has led to it's listing as a NIAID Category C Priority Pathogen for biodefense research.
Our interests lie at the interface of prokaryotic and eukaryotic biology during bacterial infections. In particular, we study human pathogen Mycobacterium tuberculosis, which is remarkably adept at subverting host immune cell function. We use genetics as a primary tool to identify bacterial genes required for pathogenesis, as well as employ a wide variety of complementary approaches to understand how the bacterium interacts with and alters its immune-cell niche, the macrophage.

How the TB bacillus interacts with host cells in order to grow during infection is not well understood.  The primary objective of the proposed research is to understand the mechanisms by which this pathogen triggers and manipulates host responses of macrophages.  Understanding how macrophages sense M. tuberculosis infection and begin to initiate the cytosolic surveillance pathway specific to virulent M. tuberculosis may help in the development of new TB treatments and diagnostics, as well as diagnostics for a broad range of infectious diseases.  Ultimately, by understanding tuberculosis pathogenesis at the molecular level, we hope to aid in the discovery of new therapies to combat and eradicate the pathogen.