Developing peptide nanomaterials as targeted endocrine therapies for brain tumours

Start date for studentships: 1 June 2014

The Institute of Biomedical and Biomolecular Science, Faculty of Science, University of Portsmouth is delighted to offer a 3 year full time studentship looking at developing peptide nanomaterials as targeted endocrine therapies for brain tumours.

Each year 38% of the EU population suffers from a brain disorder or malignancy with the incidence of malignant brain tumour in the UK being higher than the world average. Malignant gliomas are heterogenous, highly diffusely and infiltrative in nature. Despite wide surgical resection and improvements in radio- and chemotherapies, the prognosis of patients with glioblastoma multiforme remains extremely poor (median survival time of only 14.5 months from diagnosis to death). Difficulties in drug delivery across the blood-brain barrier (BBB) and low drug distribution within the tumor are primarily the main reasons for this.

The identification of the expression of G - protein coupled receptors (GPCRs) in biopsies from glioblastoma sufferers and the antiproliferative effects afforded by agonistic neropeptides makes them ideal novel therapies for gliomas. However, in order to develop these peptides as therapies for gliomas they need to reach the tumour in adequate amounts, which is not possible due to their short plasma half-life and inability to permeate biological membranes and the BBB. Peptide nanostructures produced via the self-assembly of peptide amphiphiles enables peptide delivery across the BBB and enhances their plasma stability. Entrapping cytotoxic drugs within the resulting self-assembled peptide nanostructures will enable the development of a novel endocrine strategy for delivery and targeting of cytotoxic drugs to brain tumours combined with a synergistic antiproliferative response mediated by the peptide carrier modulation of GPCRs.

The project presents an opportunity to work at the interface between bionanomaterial engineering, cellular and molecular medicine and drug delivery aiming to address challenges in relation to permeation across the BBB and translation of novel endocrine targets into targeted delivery strategies for primary malignant brain tumours. The successful candidate will gain experience in design of peptide amphiphiles in silico, solid-phase peptide synthesis and characterisation, physicochemical and morphological characterisation of self-assembled nanostructures, receptor binding assays, permeability studies across an all human in vitro BBB model, efficacy studies in glioma cell cultures expressing the GPCR receptors, and finally in vivo pharmacokinetic studies and proof of concept studies in an orthotopic xenograft rat model.

The PhD project will be supervised in collaboration with Prof Geoff Pilkington (School of Pharmacy, University of Portsmouth, http://www.port.ac.uk/institute-of-biomedical-and-biomolecular-science/cell-biology-and-pharmacology/geoff-pilkington/). The successful candidate will receive training in peptide synthesis, drug delivery, nanotechnology, physicochemical characterisation, analytical and imaging methods, cell culture, and in vivo studies.

Enquiries relating to the topic should be directed to: Dr. Aikaterini Lalatsa, School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s Building (SM5.05), White Swan Road, Portsmouth, PO1 2DT, Tel: 02392 843929, Email: [Email Address Removed].

This full-time studentship is open to Home/EU students and is located in the School of Pharmacy and Biological Sciences, University of Portsmouth. Potential applicants are advised to examine our Research Degree Pages prior to applying at:
http://www.port.ac.uk/departments/academic/graduateschool/

Applications should be submitted electronically at: https://www.registryhub.port.ac.uk/online_application/

• an application form
• a full CV including personal details, qualifications, educational history and, where applicable, any employment or other experience relevant to the application
• contact details for TWO referees able to comment on your academic performance
• a covering letter outlining the candidate’s suitability for the proposed project
Interviews: Interviews will be conducted on Monday 12 May 2014 or Thursday 15 May 2014.