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NIHNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESR01

PROTEASOMAL REGULATION AND PROTEIN QUALITY CONTROL IN M. TUBERCULOSIS

Completed
Institution
NEW YORK UNIVERSITY SCHOOL OF MEDICINE, NY
Principal investigator
Katerina Heran Darwin
Funding
$470K
Duration
2010–2026
Open portfolio

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Abstract

Tuberculosis kills nearly 2 million people globally every year. Over the years, we have determined that the Mycobacterium tuberculosis (Mtb) proteasome is essential to allow the tubercle bacilli to persist in animals. Proteasomes are multi-subunit, barrel shaped proteases that degrade proteins in a highly regulated manner. We are currently examining how proteolysis is regulated, from how proteins are tagged with the only known bacterial protein-on-protein post-translational modification to how those tagged proteins are then delivered into the proteasome core protease. Secondly, this proposal will seek to understand the functions of an essential protein quality control system that is regulated by proteasomal degradation. Identifying how this system contributes to Mtb physiology may identify new ways to combat tuberculosis infections. Thus, these studies will reveal how a proteasome senses extracellular signals to optimize bacterial growth required for lethal infections.

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R01NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESProkaryotic Cell and Molecular Biology Study Section[PCMB]proteasomalregulatedtaggedtuberculosisproteasomequality controlmtbprotein quality

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