Life Sciences & Biotechnology
Title : | Deciphering the role of CG32069 and IER3IP1 in neurodevelopment |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Neurodevelopment, Genetics |
Principal Investigator : | Dr. Sonal Nagarkar Jaiswal, CSIR- Centre For Cellular And Molecular Biology (CSIR–CCMB), Hyderabad, Telangana |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | sonalnj@ccmb.res.in |
Details
Executive Summary : | This proposal aims to identify the molecular and cellular functions of CG32069, a homologue of human Immediate Early Response 3 Interacting Protein 1 (IER3IP1), in Drosophila and human neuronal stem cells (hNSCs). CG32069 is an evolutionarily conserved gene that shares 53% identity and 73% similarity with IER3IP. It contains two transmembrane domains at C and N terminal and a G-patch domain involved in protein RNA/protein interactions. IER3IP1 has been associated with MEDS, microcephaly with simplified gyration, epilepsy, and permanent neonatal Diabetes Syndrome. Studies from yeast suggest that YOS1p might be required for protein transport between ER/Golgi. Knocking down CG32069 in larvae found that it is essential for survival and its loss leads to developmental delay with small brain. Mutant NBs loose polarity and prematurely differentiate into neurons, and they are significantly smaller than control NBs and bi/multinucleated, indicating cytokinesis failure. The researchers speculate that CG32069 might play a critical role in vesicle trafficking. They performed immunostaining for Rab11, a GTPase controlling membrane trafficking, which is required for polarity establishment and plasma membrane recycling. The study will investigate whether CG32069 is specific for Rab11 containing vesicles or a common phenomenon. It will also explore whether this function is conserved in human NSCs by expressing IER3IP1 and rescuing lethality associated with fly mutants, and knocking down IER3IP1 in hNSCs and analyzing phenotypes and processes identified in flies. This study will aid in characterization of novel genes IER3IP1/ CG32069, uncover dependent cellular and molecular processes causing microcephaly in humans, and pave the way towards understanding the vulnerability of NSCs to defective vesicle trafficking during development. |
Total Budget (INR): | 58,69,670 |
Organizations involved