Structural and biochemical characterisation of human SWI/SNF-related chromatin remodelling complexes

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The genomes of eukaryotes exist as chromatin. The organisation of chromatin provides a means of regulating access to the underlying genetic information. One way in which eukaryotes regulate chromatin conformation is through the action of chromatin remodelling motor proteins. Human forms of the SWI/SNF remodelling complex are a series of chromatin remodelling ATPases comprised of some 15 partially overlapping subunits. These complexes function predominantly at enhancers and have been observed to be mutated at high rates in a range of human cancers. Biochemical and structural characterisation of the activities of these complexes is limited. This proposal aims to address this using recombinant expressed proteins purified from insect cells. Cryo-electron microscopy will be used to characterise the structure of the complexes. Biochemical assays will be performed using nucleosomes assembled on model DNA templates. Insight into the structure and function of these complexes will help identify vulnerabilities in cancer cells where proliferation is driven by defective complexes. Project provides training in Interdisciplinary Skills.