Funding

Self-funded

Project code

PHBM3520117

Department

School of Medicine, Pharmacy and Biomedical Sciences

Start dates

February and October

Application deadline

Applications accepted all year round

This is a self-funded, 3 year full-time or 6 year part-time PhD studentship. The project is supervised by Dr Katerina Lalatsa and Prof Geoff J Pilkington.

Breast cancer remains the most common cancer among women globally, accounting for 25% of all cases. Mortality from breast cancer has been reduced by 20% in recent years, but the number of diagnoses in the developed world is rising.

Invasive forms of breast cancer can lead to metastasis in the lung, liver, bone, skin and brain (10–30% of cases). Brain metastasis is associated with the shortest survival time in patients.

Breast cancer metastatic to the brain (BCMB) is most prevalent in the triple negative tumours and Human Epidermal Growth Factor Receptor 2 (HER2+) subpopulations, since targeted therapies against HER2+ disease (such as Trastuzumab) are able to successfully control non-Central Nervous System (CNS) disease.

However, these therapies (Trastuzumab included) are unable to signifcantly penetrate the blood-brain barrier (BBB). To date, nanoparticulate technologies are the only technologies to have shown promise in delivery across the BBB and therefore in the treatment of tumours – including brain tumours.

This project aims to develop targeted endocrine peptide treatments for the treatment of breast tumours and BCMB, by targeting G-protein-coupled receptors (GPCR) over-expressed in breast tumour and brain metastatic tumour cells.

The work will include:

  • training and experience in the design of lipidised peptide analogues in silico, solid-phase peptide synthesis and characterisation, physicochemical and morphological characterisation of self-assembled nanofibers, receptor binding assays, permeability studies across an all human in vitro BBB model, efficacy studies in BCBM cell cultures expressing the GPCR receptors, and finally in vivo pharmacokinetic studies
  • access to a skills development program run by our Graduate School

Peptide therapeutics are currently unable to reach tumours in adequate amounts, due to their short plasma half-life and inability to permeate biological membranes such as the BBB.

We've already proven that peptide nanofibers produced via the self-assembly of lipidised peptides enable peptide delivery across the BBB, and possess an enhanced plasma stability which enables them to target GPCRs on the surface of brain tumour cells (Lalatsa 2015 Journal of Controlled Release 197:87–96).

We have also been able to load cytotoxic drugs into the resulting self-assembled peptide nanofibers, enabling the development of a novel endocrine strategy for the delivery and targeting of cytotoxic drugs to breast and BCMB brain tumours.

The experimental and analytical skills that you develop during this project will prepare you for future work in academia or industry.

Funding

Visit the research subject area page for fees and funding information for this project.

PhD full-time and part-time courses are eligible for the Government Doctoral Loan.

Please note, bench fees of £8,000 p/a also apply.

Entry requirements

  • A good honours degree or equivalent in a relevant subject or a master’s degree in an appropriate subject.
  • Exceptionally, equivalent professional experience and/or qualifications will be considered. All applicants are subject to interview.
  • English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

When you are ready to apply, please follow the 'Apply now' link on the Pharmacy, Pharmacology and Biomedical Sciences PhD subject area page and select the link for the relevant intake. Make sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV. Our ‘How to Apply’ page offers further guidance on the PhD application process.