Life Sciences & Biotechnology
Title : | Impact of disease-associated tubulin isotype mutations on microtubule dynamics |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Kathiresan Natarajan, Rajiv Gandhi Centre for Biotechnology (RGCB), Kerala |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | kathiresan@rgcb.res.in |
Equipments : | TC-9639 Thermal Cycler |
Details
Executive Summary : | Microtubules (MTs) are dynamic cytoskeletal polymers that support cell shape and are responsible for cell division and intracellular transport. Abnormal microtubule function is linked to various diseases, including cancer, ciliopathies, and neurodegeneration. Chemotherapeutic drugs targeting microtubules have been used to treat cancer patients. Tubulin isotype composition in neurons plays a crucial role in neuronal development and multiple functions, including migration of neuroblasts and transport in dendrites and axons. Trubulinopathies, caused by mutations in tubulin isotypes, are neurological disorders that cause neurologic abnormalities spanning both neurodevelopmental and neurodegenerative phenotypes. Tight regulation of dynamic microtubule properties is essential for maintaining neuronal architecture. Mutations in TUBA1A, TUBB2B, TUBB3, TUBB5, and TUBB4A gene families cause neuronal migration defects, such as hypomyelination. V255I, R282P, Q292K, and R391H mutations cause developmental motor and intellectual disabilities in children, and are in critical areas related to lateral and longitudinal interactions with other tubulin subunits. Isolated hypomyelination mutations lead to MT polymer instability, disrupting microtubule (MT) dynamic properties, which could lead to numerous neurological diseases. However, the involvement of tubulin isotype mutations in the development of various neurological diseases and their impact on microtubule dynamic instability remains unclear. This project proposes investigating the tubulin isotype structure/function relationship to advance our knowledge of how tubulin isotype mutations cause abnormalities in neuronal function. |
Total Budget (INR): | 31,02,840 |
Organizations involved