Research

Life Sciences & Biotechnology

Title :

Deciphering functional Ubiquitin code concerning Chlamydomonas flagellar trafficking and disassembly

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Swapnil Rohidas Shinde, Indian Institute Of Technology (IIT) Bombay, Maharashtra

Timeline Start Year :

2024

Timeline End Year :

2027

Contact info :

Equipments :

Details

Executive Summary :

The proposal investigates cilia disassembly and ciliary proteome homeostasis using Chlamydomonas reinhardtii as a model organism. The study aims to demonstrate that ubiquitination governs both processes by tagging proteins for removal. Cilia assembly and disassembly are closely related to cell cycle progression, with cilia assembled when cells exit the cell cycle and disassembled when cells re-enter. The specific molecular mechanism triggering cilia disassembly remains elusive. Studies in mammalian cells and Chlamydomonas reinhardtii have shown that the kinase Aurora-A is a central player in ciliary disassembly. Recent work suggests that ubiquitination could be another major player regulating cilia disassembly. In Chlamydomonas flagella, global ubiquitination of the ciliary proteome is elevated during cilium disassembly. Ubiquitin marks proteins for retrograde transport, and the fate of these flagellar ubiquitinated proteins is decided in the cell body. The proposal aims to characterize a ubiquitination-dependent pathway of cilia disassembly that could function along with or in parallel with the Aurora kinase A-HDAC6 pathway. Identifying novel cilia disassembly regulators might help better understand why cilia are lost during cancer progression. The proposal also addresses key questions about ubiquitinated ciliary proteins, the functional role of different types of ubiquitin chains during ciliary disassembly, and the functions of different ubiquitin readers during cilia disassembly.

Total Budget (INR):

49,60,777

Organizations involved