Post Doctoral Fellow The University of Hong Kong, Hong Kong
Abstract: Microtubules are polarized tubular structures composed principally of two proteins, the α-tubulin and the β-tubulin. Several isoforms of α and β-tubulins exist, and their expression could vary according to the cell type and the developmental stage. In this project, we study the function of tubulin isoforms such as tubulin α4A in neurons. TUBA4A cannot be tyrosinated, which was shown in-vitro to confer a higher stability to the microtubules. We hypothesize that TUBA4A could be important for neuronal development and maintenance. During ageing and neurodegenerative diseases, TUBA4A integration within the lattice might be increased to repair and maintain the stability of the neurite microtubules. In this project, we are using enhanced pluripotent stem cells (EPSC) and induced neural stem cells (iNSCs) derived neurons to examine the role of tubulin isoforms in neurogenesis, ageing, and the motor neuron disease amyotrophic lateral sclerosis (ALS). With single-molecule super-resolution microscopy, we will study the expression and integration of specific isoforms within microtubules and examine ALS pathologies in neurites and microtubule integrity in ageing. Through next-generation stem cell and organoid models, we aim to decode how tubulin isoforms contribute to neural development, neurodegeneration, and disease.
