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MRC grant for inter-disciplinary team


The MRC has awarded a grant of £830,000 to Dr Albert Basson, Craniofacial Development and Stem Cell Biology, Dr Cathy Fernandes, Institute of Psychiatry, and Dr Richard Wingate, MRC Centre for Developmental Neurobiology, to investigate the role of chromatin remodeling factors in cerebellar development and autism. The research project, which will stretch over four years, is an exciting new collaboration between these groups, combining their expertise in mouse genetics and development (Dr Basson), mouse behavior (Dr Fernandes) and cerebellar development (Dr Wingate). In addition to these groups at King’s, they will collaborate with the group of Professor Danny Reinberg, a world leader in the field of chromatin biochemistry and epigenetics at the Howard Hughes Medical Institute, New York University. Dr Basson said: ‘I am really excited about this project, as it is taking us into a completely new, but I think very important direction. The project started with a collaboration with Professor Pete Scambler, Institute of Child Health, UCL, where we were trying to test the hypothesis that a key developmental pathway, the FGF pathway, might be deregulated in mouse models for CHARGE syndrome. CHARGE is a complex syndrome characterised with a range of craniofacial, cardiovascular and brain defects. Patients also show evidence of behaviours typical of the autistic spectrum. ‘Our work in mouse models of this syndrome in collaboration with the Scambler group, has led to the identification of critical roles for the gene mutated in CHARGE syndrome, CHD7, in the development of the cerebellum. In addition to indirect links with the FGF pathway, we now have good evidence that links CHD7 to a key pathway associated with cerebellar hypoplasia and autism.’ The aim of this project will be to investigate the epigenetic mechanisms whereby CHD7 control gene expression in the developing nervous system, test whether isolated cerebellar defects in mice are associated with behavioural deficits and to investigate the role of a related gene CHD8, which is also strongly associated with autism in the human population. Opportunities for interactions between different groups have been key in establishing the collaborations that form the basis of this project, Dr Basson explained. Both he and Dr Fernandes started collaborating as a direct result of the KCL Mouse Genetics Club that was active between 2008 and 2010 and organized by Albert Basson. Funding provided by the Dental Institute and Dental Circle has allowed Albert Basson to establish close links with the Reinberg group during a short sabbatical, which is set to continue in the form of a collaboration to study the epigenetic mechanisms underlying brain development and autism risk.