Grant: Operating Grant

Cells contain several types of internal protein "skeletons", termed the cytoskeletons. One type provides structural support, while another generates force, the cellular "muscle" and "bone", respectively. We study how cells rearrange the cytoskeleton as embryos develop. We find mutations in genes controlling these processes; and by examining what goes wrong when the genes malfunction, we can infer the roles of the normal genes. Our work uses the nematode worm Caenorhabditis elegans. Its small size, the ease of growing large numbers of animals and rapid generation time make this worm ideal for genetic analysis - three recent Nobel Prizes were awarded for work on this animal. Because basic biological processes are very similar in all animals, we can use the worm to study genes in ways that are impossible with humans or other mammals. We have found a series of C. elegans genes, similar to those controlling human blood pressure and tumour metastasis, that regulate how the cytoskeleton changes cellular shapes. We also found cytoskeletal genes that are required for the accurate distribution of chromosomes to daughter cells in the specialized type of division that produces eggs. Disruption of this process in humans results in birth defects such as Down's syndrome.