Mammalian cells possess multiple closely related SWI/SNF chromatin remodelling complexes. These complexes have been implicated in multiple cellular pathways, including transcription, replication, and DNA repair. Notably, genes encoding subunits of the SWI/SNF complexes, such as PBRM1, are frequently altered in cancer and evidence supports a role for these genes as tumour suppressors. SWI/SNF complexes are important for responding to replication stress and maintaining genome stability, which are important functions in preventing tumourigenesis. However, very little is known about how the complexes are normally regulated in space and time, or how this is altered in response to replication stress. Nor is it understood how the regulation of the complexes is impaired when key subunits such as PBRM1 are absent. In this project, we will address these outstanding questions by investigating the SWI/SNF interaction landscape and its cellular dynamics.
The outcomes of the studentship include high resolution mapping of SWI/SNF complex dynamics in normal and cancer cells to elucidate the mechanisms of regulation and replication stress responses. In addition, insights into the mechanism by which PBRM1 loss leads to tumourigenesis will be generated and explored. The student will develop proficiency in cell biology, next generation sequencing-based techniques (Cut&Run and RNA-seq), proteomics (in collaboration with the Choudhary lab, ICR), and analysis of large datasets. The insights generated in these studies will yield important insights into the mechanisms by which SWI/SNF complexes prevent tumourigenesis.
Keywords /Subject Areas
Chromatin remodelling and epigenetics
Cancer biology
Proteomics and next generation sequencing
Genome instability
DNA damage responses
For details on how to apply using our online recruitment portal please see
icr.ac.uk/phds. Please note we only accept applications via the online application system
apply.icr.ac.uk
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