PhD Studentships of the North West Cancer Research (NWCR) Centre

The NWCR Centre comprises a network research groups from across the NW of England who work on basic and translational aspects of cancer biology.

The following fully funded PhD project will commence in October 2020.

“Releasing the cell cycle arrest with PROTACs to enhance DNA‐damaging therapies”.

Morgan Gadd (Lancaster University)
Sarah Allinson (Lancaster University)
Jason Parsons (University of Liverpool)

Mainline cancer treatments such as radiotherapy and chemotherapy rely on damaging the DNA of rapidly dividing cancer cells to kill the cells in preference to healthy tissues, which are non-dividing. Cancers can use cell cycle arrest proteins to halt cell division, providing them with time to repair the damage induced and thus escape the effects of the therapy. However, due to their unstable genomes and dysfunctional cell cycle regulation, cancers can be selectively sensitised to DNA-damaging therapies by releasing cell cycle arrest.

We have developed a proteolysis-targeting chimaera (PROTAC) capable of promoting cell-cycle progression in cancer cells. PROTACs are small, drug-like molecules that hijack the ubiquitin-proteasome system to degrade their targets. By doing so, the target is removed from the cell entirely, rather than simply inhibited. In this project, you will verify the activity and efficacy of our PROTAC in a number of relevant Head-and-Neck Squamous Cell Carcinoma cell lines, characterise its mode of action, and explore its potential cytotoxicity both as a single agent and in combination with various DNA-damaging therapies. In particular, we have access radiotherapy sources and the ability to use proton-beam therapy at the Clatterbridge Cancer Centre.

You will have the opportunity to develop skills and expertise in molecular approaches including cell culture, Western blot, cellular proliferation, flow cytometry, comet assays and immunofluorescence. You will be part of a dynamic research group with members working in cell biology, molecular biology, biophysics, structural biology and synthetic chemistry, and will have opportunities to develop the project in any of these disciplines as may be appropriate.

Eligibility and funding

The NWCR Centre will support a student with a three-year studentship (starting at £19,000 per annum, tax free), course fees (home/EU rate), travel and research funds. Applicants must have (or be predicted to obtain) the equivalent of a first or upper second class degree in a relevant subject, and have laboratory or research experience (either as part of or outside of a university degree course). UK and EU students are eligible. All applicants must satisfy the appropriate University English language requirements (IELTS score of 6.5).

1. Characterisation of Deubiquitylating Enzymes in the Cellular Response to High-LET Ionizing Radiation and Complex DNA Damage.
2. Structural basis of PROTAC cooperative recognition for selective protein degradation.
3. Misregulation of DNA damage repair pathways in HPV-positive head and neck squamous cell carcinoma contributes to cellular radiosensitivity.

Research Groups

1. Faculty of Health and Medicine - Dr Morgan Gadd
2. Faculty of Health and Medicine - Dr Sarah Allinson
3. Institute of Translational Medicine - Dr Jason Parsons

How to Apply

To apply please send a covering letter, full c.v. and the name, addresses and telephone numbers of two referees to horned@liverpool.ac.uk. They will be academic/industry lab heads that have direct experience of your research capabilities.

For general application enquires please contact Debbie Horne, Centre Administrator.

Closing date for applications is 30th December 2019.

Please note that interviews are scheduled for the week commencing 3rd February 2020. Travel expenses for the interview will be covered.