Cardiff School of Biosciences PhD Studentship: Design and synthesis of molecular inhibitors of c-FLIP activity as a therapeutic strategy to target breast cancer stem cells (PhD Studentship)
Reference Number: R853
Key Studentship Information
Project Title: Design and synthesis of molecular inhibitors of c-FLIP activity as a therapeutic strategy to target breast cancer stem cells
Project Description: We have recently shown that suppression of the gene for cFLIP allows the anti-cancer drug TRAIL to selectively destroy the small minority of ‘stem’ cells within a breast tumour that are responsible for new tumour growth (Piggott et al, 2011). This novel effect has potentially significant implications for the prevention of tumour spread to other organs. What is now needed is an efficient method of suppressing cFLIP in patients so that this novel approach could be tested in the clinic. The aim of this PhD project is to generate a chemical inhibitor of cFLIP that ultimately could be used as an anti-cancer drug.
First, we will perform a detailed study of the cFLIP molecule, using cell culture, molecular biology and microscopy techniques to determine which parts of the molecule are important for its regulation and where it is distributed within breast cancer cells. Second, we will use this information to identify areas on the surface of the cFLIP protein that we could bind small chemicals to interfere with its function. This will involve computer assisted modelling, drug design and subsequently, synthesis of the chemical compounds. Finally, state-of-the-art molecular assays will be used to validate the effect of these compounds on cFLIP activity within cells, as a first step towards developing a novel therapeutic agent for breast and possibly other cancers.
This is a cross-disciplinary project involving cell biology, molecular biology, chemistry and molecular modelling/drug design. The format of the project is similar to an ongoing PhD project supervised by the same PIs that is investigating an unrelated molecule associated with breast cancer. While comprehensive and expert training will be provided in all aspects of this work, we are looking for a highly motivated student who is willing to learn new and challenging techniques, some of which may lie outside of their immediate areas of training. Candidates should have a background in molecular biology, biochemistry or the pharmaceutical sciences. Practical lab experience in one or more of these areas would be an advantage.
Principal supervisor: Richard Clarkson (Cardiff School of Biosciences) Co-supervisors: Andrew Westwell and Andrea Brancale (Cardiff School of Pharmacy)
Start date of the project: 1st October 2012.
Funding
The succesful applicant will recieved full UK/EU tuition fees plus Doctoral Stipend matching UK Research Council National Minimum (£13,5 90 p.a. for 2010/11, updated each year).
This is a 3 year lab-based project funded by Cancer Research Wales.
Eligibility
Academic Criteria: The applicant should hold a First or Upper Second Class Honours BSc degree and/or a Masters degree, or equivalent degree. If English is not the applicant's native language an English Language qualification, such as IELTS is required. For IELTS an average score of 6.5 is required with a minimum score of 6 in each element.
Residency: The applicant must be eligible for UK/EU fee status.
How to Apply
Students must apply for PhD study using Cardiff's online application service. Please indicate that you would like to be considered for this studentship on your application.
Information and advice on the application process is available on the School of Biosciences website.
Application Deadline: 29th June 2012
Further Information
For more information please contact Dr Richard Clarkson on ClarksonR@cardiff.ac.uk or +44 (0)29 208 70249