Countering the proteinase-activated receptor 1 (PAR-1) pro-tumour phenotype using a novel nanotherapeutic approach

Proteinase-activated receptor 1 (PAR1) is a G-protein coupled receptor (GPCR) expressed on a number of cell types, and is activated by serine proteases such as thrombin, plasmin and activated protein C. It plays a critical role in platelet aggregation, endothelial cell activation, angiogenesis, inflammation and cell proliferation. PAR1 has also been shown to be involved in tumour angiogenesis and metastatic progression of a number of cancers including those of the breast, ovaries, lung, colon and prostate. PAR1 is also up-regulated in highly invasive tumours, correlating with metastatic potential, but not expressed in normal breast tissue. Matrix metalloprotease-1 (MMP-1) activates the PAR1-Akt survival pathway in breast cancer cells, which can be blocked using antagonists of PAR1, inhibiting tumour progression and promoting apoptosis.

This project will explore in detail the therapeutic potential of exploiting PAR1 over expression as a targeting ligand for a novel radiosensitising gold nanoparticle formulation. The PhD will be structured into three clear subsections: 1) Assessing the impact of PAR1 antagonism of novel peptide based antagonists; 2) Formulating and characterising the physical properties of a PAR1 targeted nanomedicine; 3) Assessing the in vitro and in vivo anti-tumour efficacy of the PAR1 targeted nanomedicine.

This project is well positioned within our current suite of research projects and so the appointed candidate will be well supported through the expertise of our existing group members.

The PhD candidate will be working in a well-funded nanotherapeutics group, with members from 5 nationalities.

From the start the PhD student will be involved in academic research designed to have translational/clinical application. This dual approach spans:

1) Research Skills: the academic supervisors will ensure excellent training in nanoparticle formulation, systematic physical characterisation, in vitro cell and molecular biology techniques and potentially in vivo skills.

2) Record keeping & monitoring: Monthly meetings with the student will take place with electronic records. Students must also complete a 3-month initial review and annual progress review to proceed to years 2 & 3. The annual progress review involves written work, presentation and/or mini viva. However, at each of these meetings, the primary supervisor will also be present ensuring that the maximal training benefit can be derived from these processes.

3) Additionally, there will be opportunities to present at academic meetings, building professional networks, personal development on courses for animal licenses, advanced statistics, skills which are all relevant to subsequent employment opportunities.

Impact activities include but are not restricted to presenting the research to academic and industry peers through scientific conferences and students from different disciplines through the Graduate School. The student will also engage with patients, clinicians and key stake holders through a series of webinars/focus groups to understand how they can feed and shape the research plan. Other impact activities relate to commercialisation though IP protection processes, competitor analysis and engagement with clinical collaborators.

Home applicants must meet the following academic criteria:

1st or 2.1 honours degree in a relevant subject. Relevant subjects include Pharmacy, Pharmaceutical Sciences, Biochemistry, Biological/Biomedical Sciences, Chemistry, Engineering, or a closely related discipline.

International applicants must meet the following academic criteria:

IELTS (or equivalent) of 7.0, a 2.1 honours degree (or equivalent) and a master’s degree in a relevant subject.

All postgraduate research applicants for Pharmacy who are interested in the project must submit an application all required supporting documents via the Direct Applications Portal (link below). UK students considering applying for DfE scholarship support, applications must be submitted before Monday 30^th January 2022. Any interested applicants can informally contact Dr Coulter by email at j.coulter@qub.ac.uk

https://dap.qub.ac.uk/portal/user/u_login.php