Life Sciences & Biotechnology
Title : | Structure, function and molecular mechanism studies of an evolvability factor Transcription Repair Coupling Factor in Mycobacterium spp. |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Bacterial Transcription |
Principal Investigator : | Dr. Ramanathan Natesh, Indian Institute of Science Education and Research (IISER) Thiruvananthapuram, Kerala |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | natesh@iisertvm.ac.in |
Details
Executive Summary : | The COVID-19 pandemic has led to a rise in TB cases, with 1.5 million deaths and nearly 10.6 million cases worldwide. TB is the world's top infectious disease killer, with India among the top 30 high TB burden countries. The transcription process involving RNA polymerase (RNAP) is complex and controlled by multiple regulators. A study is proposed to investigate the structural basis of DNA damage repair coupled transcription regulation in Mycobacterium tuberculosis (Mtb) and Mycobacterium smegmatis (Ms) using crystallography, single particle CryoEM techniques, and other biochemical and biophysical techniques. Transcription repair coupling factor (TRCF) is a key player in transcription-coupled DNA repair (TCR), which can be lethal if not properly managed. In humans, TCR is implicated in Cockayne Syndrome, an extreme form of accelerated aging that is fatal early in life. TRCF from Mtb is the mfd gene encoded protein of 133 kilo Daltons, while TRCF from E. coli is a multifunctional protein with helicase motifs, leucine zipper motif, and sequence similarity to UvrB and RecG proteins. The structure of TRCF (MtbMfd) is unknown, but it shares 34% identity and 50% similarity with TRCF from E. coli. MtbMfd has 78% identity to MsMfd, making it likely a TRCF. The study also proposes studying MtbMfd in complex with RNAP during transcription-coupled DNA damage recognition and repair. |
Total Budget (INR): | 51,26,000 |
Organizations involved