Defining molecular principles of tubulin isotype diversity in human health and disease
Supervisor: Dr Pleasantine Mill
Tubulin, the essential building block of cytoskeletal microtubule structures, exhibits extensive isotype diversity in metazoans. This raises the question, are all tubulins functionally interchangeable? Our recent work (Mechaussier et al medRXiv 2022) on the TUBB4B isotype has provided concrete evidence to support that tubulin isotypes play unique and essential roles in constructing specific sub-cellular populations of microtubule structures such as the centrioles and cilia studied within our lab. This PhD project will use genome engineering, cell biology, genetics and advanced imaging to examine how different isotypes are spatially organized within cells in order to better understand the ‘tubulin code’ in human health and disease. The student will also test whether different tubulin isotypes are functionally interchangeable in vivo to better understand unique and overlapping biological functions and physical properties of different tubulins.