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Telomeres and genome instability in cancer

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

We are interested in cellular processes that influence the stability of human telomeres in normal somatic cells, the germ-line and in cancer. Current research areas within the group include investigation of herpesviruses that integrated into telomeres with a focus on the consequences for the telomere and disease risk; understanding the role of DNA mismatch repair in telomere stability and investigation of the Alternative Lengthening of Telomeres (ALT) mechanism. Cancer cells maintain telomere length and thus overcome the senescence barrier that is imposed by replication dependent telomere shortening. Most tumours do this by activating telomerase, but a significant minority in particular some sarcomas activate ALT (1). We were one of the first groups to shown that the basis of the human ALT mechanism involves a recombination-like process (2), and recently advances have been made in understanding the molecular mechanism. Tumour heterogeneity following activation of a telomere maintenance mechanism (TMM) reflects ongoing genome instability and it is thought to underlie the emergence of therapeutic resistance and disease progression. The role of telomere-fusion driven instability in this process is largely unexplored and offers an exciting opportunity for a PhD research project. Through understanding these processes it may become possible to identify tumours that are more likely to develop therapeutic resistance. In this project the student will use established and novel approaches we are developing to compare mutation processes that affect telomeres and telomere-fusions and contribute to genome instability in diverse cancers. These will including chronic lymphocytic leukaemia (CLL), colorectal cancer and soft tissue sarcomas (1) that maintain telomeres via activation of telomerase or ALT. This will be complemented by experiments using cells lines. Projects in other areas of telomere molecular biology are available.

Eastley N, et al. (2017) Telomere maintenance in soft tissue sarcomas. Journal of clinical pathology.
2. Varley H, Pickett HA, Foxon JL, Reddel RR, & Royle NJ (2002) Molecular characterization of inter-telomere and intra-telomere mutations in human ALT cells. Nat Genet 30(3):301-305.
3. Mendez-Bermudez A, et al. (2012) The roles of WRN and BLM RecQ helicases in the Alternative Lengthening of Telomeres. Nucleic Acids Res 40(21):10809-10820.
4. Mendez-Bermudez A & Royle NJ (2011) Deficiency in DNA mismatch repair increases the rate of telomere shortening in normal human cells. Hum Mutat 32(8):939-946.


For other information about Royle’s lab see: http://www2.le.ac.uk/departments/genetics/people/royle/research

We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.

Funding Notes

Self funded students are welcome to apply.
Applicants should expect to hold a 1st or 2.1 BSc in a relevant field. Those holding a 2.2 degree plus a Master’s degree or >3 years relevant post-graduate experience may be eligible. Candidates with degrees from abroad are eligible if their qualifications are deemed equivalent.

Please contact Dr Royle for more information or advice about the application process.

We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.

References

http://www.ncbi.nlm.nih.gov/pubmed/28183782

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262939/

http://www.ncbi.nlm.nih.gov/pubmed/22989712

How good is research at University of Leicester in Biological Sciences?

FTE Category A staff submitted: 37.40

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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