Holes in the head: pore forming proteins in neural cell growth and migration

We have a long-established programme in pore-forming protein structural and functional biology. The system on which we have completed most work is the membrane attack complex-perforin/cholesterol-dependent cytolysin (MACPF/CDC) family of proteins found in every kind of cellular life except Archaea. Among our achievements have been the first determination of their pore structure and of a mechanism for pore-formation enabling diverse pore types to be formed by single proteins (see Gilbert et al., Trends in Biochemical Sciences, 2014 for a review).

We have recently turned our attention to members of the MACPF/CDC family which act in neural cell growth and migration. In humans, astrotactin proteins enable cerebellar neural development, while mutations within their genes are associated with a variety of diseases including the onset of Alzheimer's 5 years earlier than the median age and also susceptibility to schizophrenia and other neurodevelopmental disorders.

We recently solved the structure of a large part of human astrotactin-2 (Ni et al., 2016) and have an MRC grant to continue our work with them. A graduate studentship is available to join our dynamic, friendly and highly effective team that uses structural, biophysical, functional and cellular studies to unpick molecular mechanisms in health and disease. We benefit from excellent collaborations with labs in Oxford and abroad and you would join an exciting project at a critical stage in its development.

Contact Supervisor

Professor Robert Gilbert

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