4 Year Wellcome Trust PhD Programme: The functions of mammalian SWI/SNF related chromatin remodelling complexes.

All eukaryotes regulate access to DNA by regulating chromatin structure. One way in which this is achieved is through the action of three major forms of SWI/SNF related ATP-dependent chromatin remodelling complexes. In normal cells, these complexes act during development to establish tissue specific patterns of gene expression. In cancer cells subunits of different forms of the complex are found to be mutated at high frequency in tumours of different tissues. However, the distinct functions of the three major forms of complex are not yet known. In this proposal genome editing will be used to generate cell lines in which unique subunits of different forms of the complex can be rapidly degraded. These lines will be used to identify how chromosome structure and gene regulation is affected over time following loss of function. To investigate the action of the complexes during the inheritance of epigenetic states related experiments will be performed using synchronised cell cultures focussing on effects on chromosome structure before and after DNA replication. To track changes during development, stem cells will be subject to neural differentiation.