Life Sciences & Biotechnology
Title : | Deciphering the role of microtubule-post translational modifications in regulating lysosomal function and their implications in Cancer |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Nitin Mohan, Indian Institute Of Technology Kanpur (IITK), Uttar Pradesh |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | nitinm@iitk.ac.in |
Details
Executive Summary : | Microtubules are a common target for anticancer therapy, but their treatment can be associated with high systemic toxicity and drug resistance. To improve the specificity of MTA-based cancer therapy, researchers aim to understand the differential function of specific microtubule subtypes, such as acetylation and detyrosination, and how their dysregulations are linked to cancer. Microtubule acetylation and detyrosination selectively modulate the mechanical properties of microtubules or regulate their interactions with microtubule-associated proteins. Alterations in microtubule-PTM levels and their modifying enzymes have been linked to cancer, such as poor prognosis prostate cancer cells and metastatic breast tumors. The study investigates the mechanisms by which mt-PTMs regulate the activity of the kinase complex mTORC-1, the master regulator of cell growth and differentiation, and its hyperactivity leading to uncontrolled cell growth and cancer. The researchers found that lysosomes play a critical role in the functional regulation of two antagonistic molecular complexes-mTORC1/TSC2-to maintain cellular energy homeostasis. Preliminary data showed that a variable mTORC1 activity correlated with a variable level of acetylated and detyrosinated microtubule, with mTORC-1 bound lysosomes preferentially associated with tyrosinated microtubules under high mTORC1 activity conditions. The researchers hypothesize that distinct mt-PTM subsets and specific motor proteins regulate the differential trafficking and cellular positioning of lysosomes, controlling mTORC1/TSC2 signaling. |
Co-PI: | Prof. Pradip Sinha, Indian Institute Of Technology Kanpur (IITK), Uttar Pradesh-208016 |
Total Budget (INR): | 57,90,400 |
Organizations involved