Research

Life Sciences & Biotechnology

Title :

Histone-modification spreading to DNA repair: role of chromatin organization and reaction diffusion of DNA-binding factors

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Prof. Ranjith Padinhateeri, Indian Institute Of Technology (IIT) Bombay, Maharashtra

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

Chromatin, a polymer made of DNA and proteins, is surrounded by a dynamic cloud of transcription factors, enzymes, DNA repair factors, and other proteins that constantly interact with DNA to decide and maintain local chromatin states. Existing models do not explicitly consider the protein cloud around chromatin and its coupling with chromatin organization/chromatin state, leaving us very little knowledge about this process. This project aims to investigate the diffusion and reaction of protein molecules that interact with chromatin, their nature of organization, and how they couple with chromatin organization to decide function, particularly the spreading of histone modifications and DNA repair. Using the experimentally studied mRNA-Clr4 system, the project will simulate their spatial and temporal organization, examining how Clr4 localizes near the mat locus of S. pombe and the spreading of histone modification in the presence of diffusing clr4. Two lengthscales will emerge: one up to which the clr4 cloud is concentrated near the nucleation site, and another up to which the enzymatic-activity decides the spreading. The study will also consider another experimentally studied system of DNA double strand break detection factors (like PARP) and simulate their spatio-temporal organization near chromatin.

Total Budget (INR):

35,95,194

Organizations involved