Research Projects

The proposed project aims to identify non-tubulin proteins of different tubulin glutamylases and glycylases and understand the effect of posttranslational modification of non-tubulin substrates on specific ciliary functions and their role in human ciliopathies. Axonemes, the core structural component of mammalian cilia and flagella, are microtubule-based structures rich in tubulin glutamylation and glycylation. Defects in these modifications leading to specific ciliary phenotypes have long been attributed to defects in microtubule functions. Both motile and primary cilia are rich in hundreds of proteins, with any of these proteins being potential substrates of tubulin glutamylases and glycylases. The identity of the proteins modified within cilia and flagella is yet to be established. The project will combine molecular biology, biochemistry, cell biology, and proteomic approaches to identify the diverse non-tubulin substrates of multiple glutamylases and glycylases. The study will also study how glutamylation and glycylation of non-tubulin proteins assure ciliary and cellular functions at cell and organism level. The project will also establish the underlying molecular mechanisms of clinical ciliopathies caused due to mutations of specific tubulin PTM enzymes and determine whether observed ciliopathies are exclusive to imbalance of tubulin PTMs or other proteins. This understanding will be crucial in the long term to establish the mechanistic link underlying the pathophysiology of human disorders observed due to mutations in particular enzymes, enabling the identification of proteins and pathways that can be targeted for therapeutics in the future.