Protein modules for systematic analysis of cellular signalling pathways

Higher organisms are characterised by complex interactions between cells such as normal white blood cells that mediate immunity and abnormal cells such as in cancer. Following these interactions, signals are transmitted through interactions of many proteins, to control cell activities such as division, migration. Some of these controls fail in cancer. Thus there is considerable interest in deciphering these interactions but with the genome projects we realise that there are many proteins involved. This project utilises high throughput methods developed at the Oxford protein production Facility to provide panels of these proteins to researchers. They can then identify interactions in normal and abnormal cells and then work out how these signals are transmitted. Understanding these signals has implications for diseases such as cancer when cells grow out of control and autoimmune diseases where cells that can interact with self tissues are incorrectly controlled. Thus these interactions could be targets for therapies in the longer term.

This proposal will build on an initiative of Oxford University to set up an Oxford Module Consortium to produce high quality protein reagents for a range of research groups in several areas of cell biology. The initial focus is on proteins involved in signalling in cancer, autoimmune diseases and transplantation. The outsourcing of construct design, construction and protein production to the Oxford Protein Production Facility allows these processes to be highly efficient. This will enable individual groups to have access to panels of first rate proteins to apply to signalling projects in a systematic way. Production of other types of proteins and constructs will be evaluated. Cost recovery has already started and will contribute 20% of the costs in year one. The grant covers the period up to the OPPF renewal date (July 2008) at which point production could be scaled to meet income or ideally we envisage further expansion of the repertoire but with cost recovery this would involved only around 30% costs over 3 years.