Self-funded PhD opportunities
Developing self-assembled peptide nanomaterials as targeted endocrine therapies for tumours
- Application end date: Applications accepted all year round
- Funding Availability: Self-funded PhD students only
- Department: School of Pharmacy and Biomedical Sciences
- PhD Supervisor: Dr Aikaterini Lalatsa and Prof Geoff J Pilkington
Breast cancer remains the commonest cancer among women globally (25% of all cases). Although mortality has been reduced by 20% in recent years, the incidence is rising in the developed world. Invasive forms of breast cancer can lead to metastasis in the lung, liver, bone, skin and brain (10-30% of cases) with the latter being associated with the shortest survival time compared to other sites. Breast cancer metastatic to the brain (BCMB) is most prevalent in the triple negative tumours and HER2+ subpopulations, since targeted therapies against HER2+ disease (such as Trastuzumab) are able to successfully control non-CNS disease. However, these therapies including Trastuzumab are unable to penetrate the blood-brain barrier (BBB) in significant amounts. Nanoparticulate technologies are the only technologies to-date to have shown promise in delivery across the BBB and in the treatment of tumours including brain tumours.
The project aims in developing targeted endocrine peptide treatments for the treatment of breast tumours and BCMB by targeting GPCR overexpressed in breast tumour and brain metastatic tumour cells. However, for these peptide therapeutics to reach the tumour in adequate amounts, which is not possible due to their short plasma half-life and inability to permeate biological membranes such as the BBB. We have shown that peptide nanofibers produced via the self-assembly of lipidised peptides enables peptide delivery across the BBB and possess an enhanced plasma stability able to target GPCRs on the surface of brain tumour cells (Lalatsa 2015 Journal of Controlled Release 197:87-96). Additionally we have been able to load cytotoxic drugs within the resulting self-assembled peptide nanofibers to enable the development of a novel endocrine strategy for the delivery and targeting of cytotoxic drugs to breast and BCMB brain tumours.
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 and metastatic breast tumours. The successful candidate will gain experience and receive training in 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. The PhD project will be supervised in collaboration with Prof Geoff Pilkington http://www.port.ac.uk/institute-of- biomedical-and-biomolecular-science/cell- biology-and- pharmacology/geoff-pilkington/.
In addition you will have access to a skills development program run by the university’s Graduate School. The experimental and analytical skills developed during this project will prepare the student well for a future career in academia or industry.
Research Group Web Site: http://www.port.ac.uk/school-of-pharmacy-and-biomedical-sciences/research/
Supervisor(s): Dr Aikaterini Lalatsa and Prof Geoff J Pilkington (School of Pharmacy and Biomedical Sciences)
Funding Status: Self funded - University fees (currently, £13,100 for International Students and £4,052 for Home and EU students) + (plus additional bench fees of £6,000 - 8,000 per annum)
Search terms: Nanomedicines, Peptide delivery, Growth factors; Cancer, Brain tumours.
Click here to apply and quote project code PHBM3520117 on your application.