Life Sciences & Biotechnology
Title : | Elucidating the functional significance of the giant virus encoded non-canonical Mre11-Rad50 complex in viral DNA replication and repair using Mimivirus and Marseillevirus as model systems |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Kiran Kondabagil, Indian Institute Of Technology (IIT) Bombay, Maharashtra |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | kirankondabagil@iitb.ac.in |
Equipments : | Centrifuge
Cooling shaking incubator |
Details
Executive Summary : | The study of Nucleocytoviricota, or Nucleocytoplasmic Large DNA Viruses (NCLDVs), is relatively new, with some viruses having genomes larger than several bacteria. NCLDVs, also known as giant viruses, are a pervasive group of viruses that infect both unicellular and multicellular eukaryotes. The first virus isolated is Mimivirus, which has a large genome of 1.2 Mb. These viruses are enigmatic, as they appear to be true hybrids of bacterial and eukaryotic replication and transcription machinery, suggesting an origin likely predating the emergence of eukaryotes. These viruses code for scores of DNA repair enzymes, including a novel primase-polymerase and complete base excision repair pathway. This proposal aims to gain insights into other interesting DNA repair mechanisms in giant viruses using Mimivirus and Marseillevirus as prototypes, focusing on the double-strand break (DSB) repair pathway and Nucleotide Excision Repair (NER) that remain uncharacterized. One important DNA repair pathway found in most giant viruses is mediated by the Mre11-Rad50 system. Mre11-Rad50 complexes are nuclease-ATPase repair factors present across all domains of life, functioning in the homology-mediated DNA repair pathway to repair double-stranded DNA (DSB) breaks.
This proposal involves a thorough biochemical and biophysical characterization of the putative Mre11-Rad50 complex in Mimivirus and Marseillevirus, and elucidation of its functional significance via the gene knockout method. Structural and bioinformatic analysis will help compare the mechanism of function of the giant viral Mre11-rad50 complex in bacteria and eukaryotes, potentially helping in inferring the evolutionary origins of giant viruses. |
Co-PI: | Dr. Santanu Kumar Ghosh, Indian Institute Of Technology (IIT) Bombay, Maharashtra-400076 |
Total Budget (INR): | 55,11,000 |
Organizations involved