Brigham and Women’s Hospital (Myco3V TBRU)
Primary Investigator: D. Branch Moody, Kyu Rhee (Weill Cornell Medical College)
Website: https://tbru3v.org/
Mycobacterium tuberculosis (Mtb) has emerged as one of the world's most deadly pathogens based on the highly unusual biological and chemical properties of its cell envelope. The Mtb envelope serves as both the primary interface with, and barrier to, the human host. In human tuberculosis (TB) disease, the Mtb envelope mediates a years-long standoff and serves as the barrier to all anti-mycobacterial drugs. Yet, knowledge of its composition, variation and regulation of drug entry remains incomplete. This team of researchers has created new tools to comprehensively dissect and analyze the metabolite and lipid components of the Mtb envelope on an organism-wide basis across a large set of clinical isolates. Their aim is to provide descriptions of cell envelope variation among isolates from human patients and identify key determinants of virulence and barrier to drug action that could inform the development of better diagnostics and therapeutics. Patient-derived Mtb strains will be obtained from clinical samples collected at field sites in South Africa, where this group will implement clinically relevant technology for detection of live Mtb in exhaled (non-coughed) human bioaerosols. Studies of barrier function place special emphasis on rifampicin as a model compound due to its clinical importance as a frontline drug and role as a defining element of drug-resistant TB. The collaborative team seeks to provide better drugs and diagnostic tests, as well as a deep and durable scientific foundation for understanding of the Mtb envelope, especially the genes and molecules that control active remodeling, drug action and human host response.
For more information about the Myco3V TBRU, please see the project summaries in RePORTER:
Metabolic determinants of Mtb virulence, vulnerability and variation (U19AI162584)
- Project 1: Study of M. tuberculosis under human host selection to identify virulence and barrier lipids; Project leader: D. Branch Moody (Brigham and Women’s Hospital)
- Project 2: Metabolic determinants of barrier function in rifampin-sensitive and - resistant Mtb; Project leader: Kyu Rhee (Weill Cornell Medical Center)
- Project 3: Metabolic biomarkers of TB disease, treatment response and infectiousness; Project leader: Robin Wood (Brigham and Women’s Hospital)
- Administrative Core; Core leader: D. Branch Moody
- Core 1: Profiling and Mapping Core; Core leader: D. Branch Moody
- Core 2: Chemical Synthesis Core C; Core leader: Adriaan Minnaard (University of Groningen)
- Core 3: Bacterial Genetics Core D; Core leader: Jeremy Rock (The Rockefeller University)
- Core 4: Animal Model Core E; Core leader: Clare Smith (Duke University)