Cardiff University President's Research Scholarship: Drug Discovery: Designing and testing a novel therapeutic for breast cancer (PhD Studentship)
Reference Number: R452
Applications will be considered on a rolling basis.
Key Studentship Information
This is a Cardiff University President's Research Scholarship, part of a new £4M investment to coincide with the inauguration of Professor Sir Martin Evans (Nobel Prize for Medicine 2007) as Cardiff’s new President. All of the University Schools and Research Centres offering opportunities under the programme have demonstrated the real potential of the Scholarships to contribute to research excellence through significant, challenging and original PhD research projects and excellent PhD supervision and support. Other attractive features of the Scholarships include the presence of multiple President’s Scholars in each of the research areas and the guaranteed exposure of President’s Scholars to innovative technologies, theories, methodological approaches, and debates. More information on the President's Research Scholarships scheme is available here: www.cardiff.ac.uk/presidents
Project Title: Designing and testing a novel therapeutic for breast cancer
The project description is indicative at this stage and may be subject to change. Please contact Dr Richard Clarkson, firstname.lastname@example.org, for further information.
- An innovative and focused project aimed at generating a new therapeutic agent in breast cancer.
- Provides a truly interdisciplinary training opportunity in pre-clinical cancer research; that spans computational drug design and virtual drug screening (Brancale, PHRM), medicinal chemistry/cancer drug design (Westwell, PHRM), cancer cell biology (including target validation) and in vivo mouse modelling of breast cancer therapy (Clarkson, BIOSI).
ERBB (Her2)-positive breast cancers, which constitute around one third of all breast tumours, have a particularly poor prognosis, exhibiting resistance to first line anti-cancer drugs, and frequently developing metastatic disease – the most common cause of patient death. We have found that suppression of Bcl3, an NF-kB co-factor that modifies ERBB signalling, profoundly inhibits metastasis of these aggressive tumours in vivo and in vitro. Critically, inhibition of Bcl3 does not affect normal mammary function. These observations support the notion that targeted suppression of Bcl3 in the adjuvant or neoadjuvant setting would be a promising therapeutic approach to prevent metastatic disease in patients with aggressive forms of breast cancer.
This collaborative study aims to develop novel inhibitors of Bcl3 function and to test these in pre-clinical mouse models of metastatic breast cancer. There are currently no reported inhibitors of Bcl3 function; our drug design approach will be based on the reported crystal structure of human Pirin (Bcl3 binding partner) and model interactions with Bcl3 and p50 homodimer . This model structure will provide the starting point for defining a pharmacophore model of the critical Bcl3 ankyrin repeat domain residues that interact with Pirin. Virtual screening of the pharmacophore model against appropriate drug-like databases using a state-of-the-art 3D computational imaging suite within the School of Pharmacy and Pharmaceutical Sciences will generate virtual “hit” compounds for synthesis and antitumour evaluation. First-line compounds will be sythesised in-house and tested on panels of human breast cancer cell lines in vitro and subsequently tested in orthotopic xenograft models of ERBB+ve breast cancer within a pre-clinical modelling facility in the School of Biosciences. Compounds will be administered systemically whereupon tumour growth/regression kinetics and metastatic progression will be monitored using small bore Magnetic Resonance Imaging (MRI) within Biosciences.
This project offers a unique opportunity for training in research techniques that span the pre-clinical disciplines of drug design and in vivo drug validation that are essential for the translation of new drugs to the clinic. Due to the broad scope of the project we expect applicants to have undergraduate qualifications relevant to one, but not necessarily all of the subject areas covered by the study. Full training will be provided in all aspects of the work, by highly experienced researchers in their respective fields.
Supervisor: Richard Clarkson (BIOSI), Andrew Westwell (PHRMY), Andrea Brancale (PHRMY)
Proposed Start Date: 1st October 2012
This is a Cardiff University President's Research Scholarship. The award includes full UK/EU tuition fees plus a doctoral stipend matching UK Research Council National Minimum (£13,590p.a. for 2012/13, updated each year).
Academic Criteria: Applicants must have a First Class Honours degree or a 2.1 plus a postgraduate Masters degree (or their equivalents) in a relevant subject.
Residency: Full awards (fees plus maintenance stipend) are open to UK Nationals, and EU students who can satisfy UK residency requirements. To be eligible for the full award, EU Nationals must have been in the UK for at least 3 years prior to the start of the course for which they are seeking funding, including for the purposes of full-time education. EU Nationals who do not meet the above residency requirement are eligible for a fees-only award, provided that they have been ordinarily resident in the EU for at least 3 years prior to the start of their proposed programme of study.
How to Apply
Interested candidates should submit a CV and Covering Letter to email@example.com.
Applications will be considered on a rolling basis.
For more information contact Dr Richard Clarkson:
Telephone: 02920 870249