Dr R Bellelli, Dr S Martin
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
Efficient and accurate replication of genomic DNA is essential for all forms of life. Errors in this crucial process lead to cancer and genetic disease. A central component of the DNA replication machinery is DNA Polymerase Epsilon (Pol Epsilon), a four subunits complex required for helicase formation and leading strand replication. Two Pol Epsilon subunits, POLE3 and POLE4, remain poorly characterized in mammals. We recently uncovered the deleterious consequences of deletion of POLE4 in mice (Bellelli et al., Mol Cell 2018a). Absence of POLE4 leads to destabilization of the Pol Epsilon complex, and prevents efficient helicase establishment and origin activation, leading to aberrant development and tumorigenesis. In addition, we found that POLE3-POLE4 binds to histones H3-H4 at the replication fork, promoting chromatin replication (Bellelli et al., Mol Cell, Oct 2018b). To build on these exciting findings, the main aim of this project will be to discover how the whole Pol Epsilon complex couples DNA synthesis and nucleosome assembly and which factors cooperate with Pol Epsilon in this process. We will combine classic biochemistry and cell biology with the most innovative proteomics and sequencing approaches to unravel the molecular and cellular determinants of these two critical functions, and identify new factors required for the maintenance of both genome and epigenome stability.
A graduate with an interest in genome stability, with at least an upper second class honours degree in a relevant biological/biochemical subject, is required for this project involving the investigation of the role of DNA Polymerase Epsilon in the control of genome and epigenome stability. An MSc / MRes, or laboratory experience, in a relevant area may well prove advantageous. The project will commence ideally in September 2020 and has funding for 3 years from Barts Charity. The student will be based primarily at the Barts Cancer Institute, Barts and the London School of Medicine and Dentistry (SMD), Charterhouse Square in London.
Funding Notes
The studentship includes the following funding for 3 years:
- A tax-free annual stipend of £21,000
- Tuition fees at the Home/EU rate*
- Project consumables
*If you are considered an overseas student for fee purposes, you are welcome to apply for this studentship, however you will be required to cover the difference in tuition fees
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