China Scholarship Council: The role of epigenetic regulators in cancer


   School of Life Sciences

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  Prof Tom Owen-hughes, Dr Gabriele Schweikert  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The advent of population-based genome sequencing has made it possible to identify tumour suppressors and oncogenes systematically. A surprising outcome of such studies is that numerous factors acting at the level of chromatin act as tumour suppressors. This includes subunits of ATP-dependent chromatin remodelling complexes. These complexes act to regulate access to chromatin at many locations. They are often multi-subunit complexes and different subunits of related complexes act as tumour suppressors in different tissues (1). Acute depletion using proteolysis targeting chimera’s (PROTAC’S) or degron systems provides a means to study the pathway by which these factors act as tumour suppressors (2), (3). In this project we characterise the pathways via which loss of function to subunits of chromatin remodelling complexes drives cancer. The aim will be to identify points at which it is possible to intervene in the activation of oncogenic pathways following loss of these subunits.  

The project will provide training in the culture and genetic manipulation of stem cells including differentiation to relevant organoid models and the use of genome editing. We use functional genomics approaches such as ATAC-seq and ChIP-seq, (single cell) transcriptomics and proteomics to characterise the changes occurring following acute loss of these subunits. Analysis of the data generated will provide experience in the use of high-performance computing and bioinformatics tools.  

Biological Sciences (4)

Funding Notes

In order to be eligible for these awards applicants must:
Be a Chinese national
Meet the requirements of the CSC – please see their website
Hold an unconditional offer to study for a PhD at the University of Dundee and meet our English language requirements
Have completed a bachelors or masters degree before the agreed start of PhD study
Already have an IELTS score of 6.5 at time of applying
For further information on the CSC programme please visit https://www.dundee.ac.uk/phds/funding/china-scholarship-council-csc-programme and apply by completing our application form - https://dundee.onlinesurveys.ac.uk/csc-programme-2024-entry

References

1. Exploiting epigenetic vulnerabilities in solid tumors: Novel therapeutic opportunities in the treatment of SWI/SNF-defective cancers.
Chabanon RM, Morel D, Postel-Vinay S.
Semin Cancer Biol. 2020 Apr;61:180-198. doi: 10.1016/j.semcancer.2019.09.018. Epub 2019 Sep 27.
PMID: 31568814
2. Acute depletion of the ARID1A subunit of SWI/SNF complexes reveals distinct pathways for activation and repression of transcription.
Blümli S, Wiechens N, Wu MY, Singh V, Gierlinski M, Schweikert G, Gilbert N, Naughton C, Sundaramoorthy R, Varghese J, Gourlay R, Soares R, Clark D, Owen-Hughes T.
Cell Rep. 2021 Nov 2;37(5):109943. doi: 10.1016/j.celrep.2021.109943.
3. BAF complex vulnerabilities in cancer demonstrated via structure-based PROTAC design. Farnaby W, et al., Nat Chem Biol. 2019 Jul;15(7):672-680. doi: 10.1038/s41589-019-0294-6. Epub 2019 Jun 10.
PMID: 31178587

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