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Abstract: The genomes of all eukaryotes encode members of an extended family of ATPases that act to arrange chromatin so as to allow appropriate access to the underlying DNA. The ATPases act as components of molecular motors that drive DNA across the surface of nucleosomes. Most recently we have been using single particle cryo-Electron Microscopy to study how enzymes in this protein family engage with nucleosomes. Initially these studies focussed on the yeast protein Chd1 that represents a relatively simple and tractable member of the protein family. However, as this work is ongoing it has become clear that another member of the protein family, human forms of the SWI/SNF complex is mutated at high frequency across a range of different cancers. Interestingly, different subunits of the same complex are mutated at high frequency in tumours of different tissues. As a result our focus is shifting to studies of human forms of the SWI/SNF complex. Our initial studies indicated that in clear cell renal carcinoma where the PBRM1 is mutated in around 40% of tumour samples, we detect deficiencies in other subunits at the protein level. Our ongoing work is aimed at providing understanding into how loss of specific subunits results in tissue specific cancer.

Biography: Tom Owen-Hughes studied as postdoctoral researcher at Pennsylvania State University in the Lab of Jerry Workman. It was here that he established an interest in studying how chromatin is reconfigured during gene regulation. In 1998 he started an independent lab at the Centre for Gene Regulation and Expression in Dundee. Here he has studied how chromatin remodelling ATPases regulate chromatin structure using a range of experimental approaches including functional genomics, biochemistry and structural biology.