Competitive three year full time studentship in the Department of Biological and Medical Sciences
Research title: Exploring drug delivery routes for a novel aspirin prodrug.
Main Supervisor Dr David Meredith
Eligibility: Only open to UK/EU applicants (who must be permanently resident in UK/EU)
Start date: 23rd January 2017
Bursary: £14296 pa (pro rata as January start) for academic year 2016/17 & fees
Closing date: 12th October 2016
Applicants should be of the highest quality and capable of submitting a PhD thesis within 3 years. Requirement a good Honours degree (2.1 or equivalent).
It is preferred that EU applicants have a valid IELTS Academic test certificate minimum score level 6 in each of the four areas of reading, writing, listening and speaking with overall minimum score 7.0 issued since the 23rd April 2015 by an approved test centre please see web site below. Or an undergraduate degree awarded by a recognised UK university within the last two years. https://www.gov.uk/government/publications/guidance-on-applying-for-uk-visa-approved-english-language-tests
Exceptionally we are prepared to consider alternative acceptable written evidence of English language ability.
The non-steroidal anti-inflammatory drug (NSAID) aspirin is a highly effective drug, best known for its anti-pain/inflammatory properties, but also widely prescribed for its cardiovascular protective functions against heart attack and stroke. However, despite its widespread use and therapeutic effectiveness, aspirin shows considerable toxicity to the gastrointestinal (GI) tract, with bleeding and ulceration as the main symptoms. To overcome these effects non-toxic NSAID prodrugs have long been sought, but with little success due to two major obstacles. The first is to design a prodrug which will release the active form of the NSAID in vivo. The second obstacle is that ideally the prodrug needs to be absorbed into the body intact, ie before metabolism to avoid local intestinal damage by the free drug. The human membrane transporter PepT1 (SLC15A1) is expressed at high levels in the small intestine, where it is responsible for the uptake of dietary di- and tri-peptides. In addition, it also carries a number of therapeutically important drug compounds, including beta-lactam antibiotics, and is known to be able to transport a wide range of chemically diverse peptide mimetic compounds. Recent studies in our laboratory have demonstrated the potential for using PepT1 as a route for delivering peptide-conjugated drugs (ie prodrugs), and we have continued this approach to design a novel peptide-conjugated prodrug of aspirin.
Therefore the AIM of this project is to develop novel peptide-conjugated prodrugs of aspirin, developed in collaboration with the University of Keele. The prodrugs will be tested for their transport and pharmacological properties, using a variety of techniques including protein expression, cell culture, enzymology and HPLC. Other compounds and site-directed mutagenesis will also be employed to further our understanding of how PepT transporters function.
As part of their Studentship, any successful applicant will be required to undertake up to 6 hours undergraduate teaching/demonstrating a week during semesters on undergraduate practicals without further remuneration. Training will be given.
Further information on the project please contact Dr David Meredith
e-mail address [email protected]
How to apply
Please complete the Application Form, which you can download from http://www.hls.brookes.ac.uk/images/research/phd-studentship-application-form-jan-14.doc
With your application please enclose a CV and scanned copy of your degree certificates and transcripts and letter from awarding body plus two signed academic references. Additionally if appropriate a valid IELTS Academic test score certificate.
Please carefully note that applications only accepted by e-mail to the following address: [email protected]
YOU MUST NOT SEND ANY QUERIES, APPLICATION, CV OR OTHER DOCUMENTATION VIA FINDAPHD