Research

Life Sciences & Biotechnology

Title :

Role of Nuclear mTOR: An Autonomous Modulator of Gene Expression

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Smrati Bhadauria, CSIR-Central Drug Research Institute (CSIR-CDRI), Uttar Pradesh

Timeline Start Year :

2022

Timeline End Year :

2025

Contact info :

Equipments :

Details

Executive Summary :

The mechanistic target of rapamycin (mTOR), a master regulator of cellular responses, is known to control various processes such as cell growth, proliferation, autophagy, cytoskeletal reorganization, and metabolic reprogramming through two well-studied canonical cascades. mTOR can also influence gene transcription without gaining access to the nucleus via terminal effector molecules that activate downstream transcription factors. Recent studies have shown evidence in support of nuclear presence of mTOR, which is a potential transcriptional modulator. The intrinsic kinase activity of mTOR allows it to phosphorylate and activate key components of transcriptional machinery and functionally modulate key components of epigenetic regulatory mechanisms. Recent discoveries, such as acetyltransferase p300 being phosphorylated by mTORC1, support a crosstalk between mTOR and epigenetic regulatory mechanisms. Preliminary studies have observed time-dependent increases in nuclear levels of mTOR²⁴⁸¹ and mTOR²⁴⁴⁸, as well as increased phosphorylation of Histone H3 at Ser¹⁰ following mTOR stimulation. The current project aims to analyze this effect and determine if nuclear mTOR may modulate gene expression at the transcriptional level, with a focus on its potential crosstalk with epigenetic regulatory mechanisms and potential transcriptional partners.

Total Budget (INR):

30,74,792

Organizations involved