Nematode Functional Genomics

Alan Coulson has two main roles at the Sanger Centre, revolving around the worm and the human genome projects. Although the worm sequence is essentially finished, the tidying-up of that and the physical map is ongoing. There is also a continuous need for communication with the worm field with regard to information and materials relating to the sequence project. For example, the cosmids and YACs of the physical map continue to be, as they have been for many years now, an extremely powerful resource, and the Sanger Centre distributes in the order of 500 clones per month to the community. Alan is team leader of the worm functional genomics group, which is currently small but will be expanding shortly. Patricia Kuwabara is a member of the team and a description of their activities can be found below. The Human Genome Project is sequencing mapped PAC and BAC clones. Alan's primary involvement is with the team that is responsible for subcloning the 10 000 or so clones that will be required to complete the one-third of the genome sequence to be contributed by the Sanger Centre. Patricia Kuwabara has been using Caenorhabditis elegans as a model for understanding how protein–protein interactions regulate cell-to-cell signalling. Her research has focused on understanding the molecular mechanisms underlying the genetics of C. elegans sex determination. This work has led into a study of regulated proteolysis involving calpains and also into the roles of the multiple C. elegans Patched proteins, which in other organisms have been shown to be receptors for the Hedgehog morphogen. In addition, the group is taking advantage of the completion of the C. elegans genome sequence to develop whole genome DNA microarrays for expression profiling. At the Sanger Centre, DNA microarrays are providing opportunities to examine how development and physiology are regulated globally, because most nematode genes have now been identified at the sequence level. The group are being assisted in this endeavour by Dr Stuart Kim (Stanford, CA).