Cambridge Institute for Medical Research

Professor Geoff Woods

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We find gene mutations that cause Mendelian human disease, particularly those affecting in brain size and pain perception. For this purpose we have developed methods of linkage, mutation detection and bio-informatics. Once a human disease gene is identified we determine the function in normal development and find out how mutations cause the exact phenotypes seen in disease.

Our predominant focus is autosomal recessive primary microcephaly (MCPH). The MCPH brain is small but architecturally normal and the only phenotype is mental retardation – which can be mild to severe. MCPH is therefore a model disease in which to seek genes that are critical to, and non-redundant for, prenatal brain growth. The MCPH genes seem to act in the neuro-epithelium lining the interior of the brain, and from which the majority of neurones arise in foetal life. Our initial focus was to find the MCPH genes, now we are trying to find what these genes do and how perturbation of this process leads to microcephaly. It seems likely that a number of mechanism will cause MCPH but completely unexpectedly all MCPH genes encode centrosomal components – emphasising a critical role for the centrosome in organising neurogenesis. Our functional studies predominantly involve human embryonic brain expression, cloning and expression in cell lines and studies of mitosis. We are also part of a wider collaboration network determining the role of the centrosome in neurogenesis, with,

• Dr Fanni Gergely, CRUK, Cambridge, Centrosome Biology
• Professor Weiland Huttner, Max Plank Dresden, Mouse Embryonic neurogenesis.
• Professor Susan Lindsay, Centre for Life in Newcastle, Human Embryonic Brain Neuro-anatomy.
• Professor Chris Walsh, Harvard, Genetics of Human Neurodevelopmental Disorders.

We have more latterly become involved with individuals who don’t feel pain. Whilst very rare, these people need early diagnosis and very careful management. We have found a gene that cause Congenital insensitivity to Pain, are seeking further human pain genes and study the functional consequences of mutations in a number of pain genes, e.g. SCN9A and NGFB.
Finally, our work directly benefits families, as we can offer clinical information and DNA testing for the disease we study.

Funding

• Wellcome Trust
• Pfizer (pain studies only)
• Birth Defects Foundation

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