Cancer Research UK Imperial Centre
PhD Studentship in Tumour Biology
Imperial College London
South Kensington and Hammersmith (East Acton) Campuses, London, UK
Applications are invited for a PhD studentship funded by Cancer Research UK,
commencing October 2015 for the project:
RSK4 targeting: a new therapeutic strategy against both drug resistance and
metastasis in lung cancer
The project will be split between the Departments of Surgery & Cancer (Hammersmith
Campus) and of Life Sciences (South Kensington Campus), world leaders in cancer
research, cell and molecular biology, metabolomics, imaging and structural biology.
The Project: Lung cancer is the commonest cancer killer worldwide due to the onset of
drug resistance and metastatic disease. We have identified the kinase RSK4 as a
mediator of both these processes. Indeed, silencing of this protein sensitises lung cancer
cells to chemotherapy and prevents their invasiveness in vitro and in zebrafish. The clinical
relevance for this was underlined by the overexpression of this kinase in lung cancer
specimens and its association with poor patients’ survival. Hence, RSK4 is a promising
novel therapeutic target in lung cancer. Through drug screening, we identified
trovafloxacin as a potent allosteric inhibitor of RSK4 activation in vitro and in cells. Now,
we intend to further the case for RSK4 targeting as a promising anti-cancer therapeutic
strategy by (1) demonstrating its potential in lung cancer mouse models using both
CRISPR technology and trovafloxacin administration, (2) co-crystallising RSK4 with
trovafloxacin to inform chemical derivatisation and obtain more potent/selective inhibitors,
(3) clarifying the underlying molecular mechanism of action of RSK4 to provide potential
biomarkers of RSK4 targeting and (4) assessing the role of RSK4 in additional cancer
types to refine our understanding of the breadth of therapeutic indications of inhibiting this
kinase. This multidisciplinary project will address an area of unmet therapeutic need and
identify a novel strategy for the treatment of lung cancer, a CRUK strategic priority. Data
from this project may also be the basis for further investigation into the potential for RSK4
targeting in other tumour types.
Studentship Details: The award is for 48 months (full time) and covers course fees at the
Home/EU rates and a tax-free stipend of £21,000. Applicants must hold (or obtain by
October 2015) a First Class or an Upper Second Class degree (or equivalent overseas
qualification) in a Life Sciences discipline, and Imperial would normally expect successful
applicants to hold or achieve a Master's degree in a related field. Prior experience in
structural biology is not essential but experience in mammalian cell culture and molecular
biology techniques would be preferred.
Non-EU applicants, if successful, will be responsible for payment of fees at the overseas
rate (currently £30,000 per annum). Funding for overseas fees is not provided.
For informal enquiries please contact Dr Olivier E Pardo (o.pardo@imperial.ac.uk). For
application, please send a full CV, stating your nationality, and the full contact details of
two academic referees to CR-UK.Centre@imperial.ac.uk. We regret that due to the large
volume of applications received, we are only able to notify those shortlisted for interview.
The deadline for applications is 4th Sept 2015.