Life Sciences & Biotechnology
Title : | Dissecting the role of Rv1899c, an HDAC1-ZBTB25 interacting protein of Mycobacteria in downregulating the expression of macrophage IL-12B during Mycobacterium tuberculosis infection |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Immunology, Host-Pathogen Interaction |
Principal Investigator : | Dr. Aravind Madhavan, Amrita School Of Biotechnology, Vallikkavu, Kerala |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | aravind7933@gmail.com |
Details
Executive Summary : | Tuberculosis (TB) is a significant global disease, particularly in tropical regions. Despite the use of anti-TB drugs and BCG vaccines, TB remains a global disease that cannot be eradicated. To manage TB, it is crucial to identify potential antigens that offer survival advantages by overwhelming host defenses. Autophagy, a major player in altering host-directed therapy, has been reported to disrupt mycobacteria survival inside cells. Identifying antigens that hinder autophagy and understanding their mechanisms of action could enhance drug discovery research in TB therapeutics. A previous study found that HDAC1, a gene suppressor, suppresses histone H3 at the IL-12B gene promoter in macrophages and suppresses its transcription upon TB infection. The study also found that transcriptional repressor ZBTB25, Sin3a, and bacterial protein Rv1899c associate with the phosphorylated HDAC1 silencing complex, which downregulates its expression in infected macrophages. Pharmacological inhibition of HDAC1 and ZBTB25 promoted colocalization of MTB and LC3 in autophagosomes, leading to the killing of intracellular MTB.
The proposed project aims to identify the role of Rv1899c in regulating autophagy through the HDAC1-ZBTB25-Sin3a complex in mycobacteria infected cells and its effect on intracellular survival in vitro and in vivo. The study will first identify the direct or indirect effect of Rv1899c on HDAC1-ZBTB25-Sin3a complex formation, then unravel the intricate control of autophagic response by Rv1899c through HDAC1-mediated silencing complex formation and its consequence on mycobacterial growth inside macrophages. |
Total Budget (INR): | 29,00,830 |
Organizations involved