3 Year Full Time Studentship - Exploiting the Potential for Drug Targeting and Delivery by Mammalian Peptide Transporters of the SLC15 Family

Oxford Brookes University - Department of Biological and Medical Sciences

Faculty of Health and Life Sciences

3 Year Full Time studentship

Eligibility: Home UK/EU applicants who must be permanently resident in UK/EU

Closing date: 12 January 2018 (midnight UK time)

Start Date: September 2018

Value p.a.: Bursary of £14,500 (for 2017/18) and fees.

Main supervisor: Dr David Meredith

Project title: 

The human membrane transporter hPepT1 (SLC15A1) is expressed at high levels in the small intestine, where it is responsible for the proton-coupled uptake of dietary di- and tri-peptides. In addition, hPepT1 carries a number of therapeutically important drug compounds, including beta-lactam antibiotics, and also transports 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), such as cyclosporine. Although there are no mammalian peptide transporter crystal structures, the recently solved bacterial structures have been used to create homology models that will be tested. 

Therefore the aims of this project are

  • To investigate the structure-function of hPepT1 expressed in Xenopus oocytes, using a variety of techniques including site-directed mutagenesis and two-electrode voltage clamping; and
  • To continue to investigate the transport of novel substrates and prodrugs to further enhance our understanding of hPepT1 potential as a route of drug delivery.

The novel contributions to knowledge that will be gained through this project will include gaining further insight about the substrate specificity of human PepT1, developing transported prodrugs, and increasing our understanding of the transport mechanism at the molecular level.

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.

Contact: Dr David Meredith (dmeredith@brookes.ac.uk)

Requirements: Applicants should be of the highest quality and capable of submitting a PhD thesis within 3 years. Applicants should have a first class or upper second class (minimum 2.1) honours degree from a Higher Education Institution in the UK or an acceptable equivalent qualification. EU Applicants must have an IELTS Academic test certificate with an overall minimum score of 7.0 and no score below 6.0 issued since 12th January 2016 by an approved test centre. We will consider alternative acceptable evidence of English Language ability.

www.gov.uk/government/uploads/system/uploads/attachment_data/file/491093/2016-01-11_-Approved_Secure_English_Language_Tests_and_Test_Centres_-_Website.pdf

Application procedure:

Applications only to hlsapplications@brookes.ac.uk

Download application form:

(www.hls.brookes.ac.uk/images/research/phd-studentship-application-form-jan-14.doc)

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Type / Role:

PhD

Location(s):

South East England