PhD Study : Functionalised gold surfaces for cancer therapy.

Summary

Gold nanoparticles (AuNP) with diameters of ~15nm can be readily synthesised in the laboratory and are the subject of a concerted international research effort, focused on developing new cancer therapies, with the aim of obtaining lower dosages and smaller side effects. For such a nanoparticle-delivery system to function effectively it must be capped with ligands to prevent capture by the immune system and to target and enter tumour cells. Generally these functions cannot be delivered by a single ligand and, hence, the development of these systems requires dual functionalization, attachments of typically a poly-ethylene glycol (PEG) ligand, to escape the immune system and also a peptide ligand to facilitate cell entry. At present the methods to prepare and analyse these ligand-functionalised particles are not fully developed, most notably, the arrangement and size of the ligands on the AuNP is still unknown.

This project tackles this issue for gold nanoparticles (AuNP) functionalised with PEG and peptide ligands, which represents a candidate system for the development of prostate cancer drugs. It will use principally atomic force microscopy (AFM) in a liquid environment. The supervisory team has well-established research expertise in AFM and SEM microscopy (P Lemoine), functionalisation of AuNP (D. Dixon) and cell biology (G Burke). It follows from an existing collaboration between Lemoine and Dixon, which has already yielded preliminary results on the AFM analysis of AuNP and an ongoing re-submission of an EPSRC proposal.

The rationale for this study is that, alternative solution analysis techniques used to date (FTIR, DLS, Zeta-potential) only give indirect information on size and arrangement.

The objectives of this project are;

1.To determine size and arrangement of competing PEG and peptide ligands on gold thin film surfaces using AFM microscopy and low kV field emission SEM microscopy. We will also study how blood proteins adhere to these surfaces to investigate their likely biological response.

2.To investigate these ligands on colloidal AuNP solutions, using, amongst others, the aforementioned solution analysis techniques.

3.To prepare and characterise ligand-functionalised AFM probes.

4.To use force spectroscopy and lateral force microscopy to analyse the interactions of these AFM probes with self-assembled AuNP layers and surface-immobilised cancer cells.

The overall delivery of the project is a better understanding of the arrangement and size of competing PEG and peptide ligands on AuNP as well as their interactions with cancer cells. This knowledge will result in more efficient functionalisation recipes, which will be tested in D. Dixon’s group, by well-established biological protocols as well as high-impact publications and RC funding bids. The proposed research is also aligned on the ‘healthy communities’ theme identified in the ‘five and fifty’ UU strategic plan, as well as its declared strategic priority to focus on research with impact.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living