Wellcome Trust PhD Programme for Clinicians at the University of Cambridge: 'The cell biological and developmental roles of microcephaly-associated genes within the developing zebrafish central nervous system'. (360G-Wellcome-090659_Z_09_A)

My project aims to investigate the cell-biological basis of abnormal neurogenesis and reduced brain size caused by mutations in genes associated with microcephaly including ASPM, CDK5RAP2, CENPJ, STIL, MCPH1 and PCNT. These genes all encode centrosomal proteins and they are thought to be important in the control of neural proliferation, although their precise roles in central nervous system (CNS) development and regulation of brain size are not known. To investigate this question I am working on embryonic Zebrafish retina as a model for the developing CNS due to its experimental accessibility and amenability to genetic manipulation as well as in vivo confocal time-lapse imaging. FolIowing morpholino-induced gene knockdown or expression of dominant negative constructs I will examine in detail their cell biological roles. These may include regulation of the symmetry of cell divisions and/or cell cycle dynamics. These studies will contribute to our understanding of human microcephaly and nervous system development.