Dr D Williamson
No more applications being accepted
Funded PhD Project (European/UK Students Only)
About the Project
Medulloblastoma accounts for 10% of childhood cancer deaths and there remains an urgent need for innovative therapies which could lead to improved outcomes. Clinical challenges encompass both the need to improve survival rates (currently approximately 70%), and to reduce therapy-related toxicities in surviving patients [1].
Recent advances in our understanding of medulloblastoma biology have identified a number of critical biological pathways in tumour development, and this has led to initiatives to target these pathways therapeutically using novel pathway-specific drugs [2].
This project aims to use contemporary molecular tools and experimental disease models to identify effective drug combinations which could be advanced towards clinical use for medulloblastoma. Gene editing using the CRISPR-CAS9 system [3, 4] provides an exciting new tool, which allows us to systematically assess the functional impact of each gene in the human genome on disease behaviour (e.g. tumour growth or drug response). We will apply this technology to our novel cell-based models of critical biological changes in medulloblastoma (e.g. MYC), and use these to identify candidate combination therapies and genetic dependencies, which could be exploited to target MYC-dependent tumours. This will be done using anti-MYC drugs and inducible MYC models in combination with CRISPR-CAS9 to identify second targets which could be used in combination with anti-MYC drugs to improve anti-tumour effects.
Background to host institution: The Northern Institute for Cancer Research (NICR) is the focus of research excellence in translational cancer research at Newcastle University with over 250 personnel and an annual research income of between £8m and £10m. In 2009, the Institute successfully applied to become a Cancer Research-UK (CR-UK) supported Cancer Centre.
The paediatric brain tumour research group: The NICR paediatric brain tumour group, led by Prof. Clifford, Dr. Williamson and Prof. Bailey, comprises over 20 scientists and clinicians. The group is supported by project and clinical trials grants including a programme grant from Cancer Research UK (£1.3M over 5 years), core funding from North of England Children’s Cancer Research (£250K per annum), and the group leads the new £4M INSTINCT network programme.
Supervisors
Professor S Clifford, NICR, http://www.ncl.ac.uk/nicr/staff/profile/steve.clifford
Dr D Williamson, NICR, http://www.ncl.ac.uk/nicr/staff/profile/daniel.williamson
Prof Simon Bailey, NICR, http://www.ncl.ac.uk/nicr/staff/profile/simon.bailey
Candidates must have a BSc in an appropriate biological sciences discipline at first or 2:1 level, or a Masters degree in a relevant subject (e.g. cancer research, bioinformatics).
You must apply through the University’s online postgraduate application form - http://www.ncl.ac.uk/postgraduate/apply/. Only mandatory fields need to be completed. However, you will need to include the following information:
• insert the programme code 8300F in the programme of study section
• select ‘PhD in the Faculty of Medical Sciences – Cancer Research as the programme of study
• insert the studentship code CR071 in the studentship/partnership reference field
• attach a covering letter and CV. The covering letter must state the title of the studentship, quote the studentship reference code CR071 and state how your interests and experience relate to the project
• attach degree transcripts and certificates and,if English is not your first language, a copy of your English language qualifications
Funding Notes
Sponsor:This studentship is funded by Blue Skye Thinking
The award covers University fees at the Home/EU rate and a stipend of £14,196 (2015-16) for the four-year duration of your PhD. International students may apply but must fund the difference between the Home/EU rate and the overseas rate.
Project Start Date: November 2015.
References
*Publications from the Newcastle Paediatric Brain Tumour Group and collaborators.
*1. Pizer BL and Clifford SC. The potential impact of tumour biology on improved clinical practice for medulloblastoma: progress towards biologically driven clinical trials. Br J Neurosurg. 2009; 23(4):364-375.
*2. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, Eberhart CG, Parsons DW, Rutkowski S, Gajjar A, Ellison DW, Lichter P, Gilbertson RJ, Pomeroy SL, Kool M and Pfister SM. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012; 123(4):465-472.
3. Sanchez-Rivera FJ and Jacks T. Applications of the CRISPR-Cas9 system in cancer biology. Nat Rev Cancer. 2015; 15(7):387-395.
4. Xue W, Chen S, Yin H, Tammela T, Papagiannakopoulos T, Joshi NS, Cai W, Yang G, Bronson R, Crowley DG, Zhang F, Anderson DG, Sharp PA and Jacks T. CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature. 2014; 514(7522):380-384.
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