Research

Life Sciences & Biotechnology

Title :

Understanding the regulation of gap junction protein Connexin 43 in Murine-beta-Coronavirus, MHV induced acute and chronic phase inflammation by combining TNF-alpha, IL-10 and TGF- beta signalling triad.

Area of research :

Life Sciences & Biotechnology

Focus area :

Cell Biology

Principal Investigator :

Dr. Jayasri Das sarma, Indian Institute of science Education and Research (IIsER) Kolkata, West Bengal

Timeline Start Year :

2024

Timeline End Year :

2027

Contact info :

Details

Executive Summary :

The COVID-19 pandemic has led to the development of therapeutics to control the spread of highly pathogenic human coronaviruses. A recent study from the PI's laboratory has found the therapeutic potential of a host gap junction protein connexin 43 (Cx43) against MHV-A59, highlighting the importance of Cx43 expression at the cell surface to reduce MHV infectivity and spread. The study aims to investigate the mechanism behind altered Cx43 expression, using the MHV-A59-induced disease as a model for viral-induced demyelination, which mimics the pathological hallmarks of human neurological disease Multiple sclerosis. The proposed proposal explores the regulation of Cx43 expression by the balance between pro-inflammatory (TNF-alpha) and anti-inflammatory (TGF-beta1 and IL-10) signaling pathways, using the established MHV-induced model. The researchers aim to further dissect the downstream signaling of TNFalpha-TGFbeta1 and IL-10 in controlling Cx43 expression and modulate these cytokines or their downstream pathways to develop a cytokine-based therapy to stabilize Cx43 expression in the CNs, potentially reducing acute stage beta-CoV infectivity and spread and reducing chronic stage demyelination.

Total Budget (INR):

47,32,400

Organizations involved