Life Sciences & Biotechnology
Title : | MitoInfect: An integrative Approach to Dissect Mitochondria associated Host-Pathogen Interactions |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Anshu Bhardwaj, CSIR – Institute Of Microbial Technology (Imtech), Chandigarh |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | anshub@osdd.net |
Details
Executive Summary : | Mitochondria are involved in several significant cellular processes like energy metabolism, autophagy regulation, immunomodulation in response to infections, etc. These processes are interlinked to the dynamic status of mitochondrial morphology and function. Under normal conditions, mitochondrial exists as a network of elongated rod-shaped entities, which under pathological conditions leads to an abnormal mitochondrial structure and cell activity. Many pathogens influence and modulate mitochondrial function in order to create a replicative niche in the cell. It is shown that Mycobacterium tuberculosis (Mtb) infection leads to mitochondrial damage perturbing the equilibrium of pro- and anti-apoptotic factors leading to mycobacterial dissemination. Similarly, loss of mitochondrial membrane potential is reported in case of Shigella infections. It has been shown that viral infections like Dengue or SARS-CoV-2, leads to inhibition or degradation of a mitochondrial fission factor DRP1, which limits host cell’s IFN responses. Similarly, HCMV and measles virus enhance mitochondrial function towards persistent infections. Thus, there are significant and varied differences in infection mechanisms across different bacteria and viral pathogens and reasons for this multiple interaction interfaces is not yet fully understood. What we do understand is that mitochondrial reprogramming occurs when cellular microenvironment is challenged with infections and when there are mutations either in the mitochondrial genome or the nuclear genome encoding mitochondrial proteins. It is also important to mention here that patients with mitochondrial diseases often experience more frequent and severe infections. This indicates that in addition to neurodegenerative and metabolic disorders, mitochondrial dysfunction also plays a significant role in infectious disease predisposition. The current proposal aims at understanding the landscape of proteins involved in mitochondrial dysfunction and their interspecies interactions across a wide range of bacterial and viral pathogens. Genomic variation of the interacting partners will offer insights into differential infection predisposition states which can be critical to predict co-morbid conditions. These observations can provide a strong foundation for exploring new antimicrobial therapies as well as markers of infection predisposition. Also, study of interspecies interactions enable identification of common molecular signatures across diverse phenotypes and disease pathologies via gene-disease and host-pathogen interaction networks and provide a comprehensive assessment of mechanisms of infection which are exploited by microbes. To the best of our knowledge, there is no systematic evaluation performed till date to correlate variations in primary mitochondrial diseases with infection predisposition to bacterial or viral infections. |
Total Budget (INR): | 21,96,201 |
Organizations involved