Summary

There were 750 new cases of eye cancer in the UK in 2014, that’s around 2 cases diagnosed every day. It is now widely accepted that melanoma is better treated by a multifaceted combination therapy strategy. Aside from surgery, radiotherapies are currently available for ocular melanoma; particle beam, transpupillary thermotherapy, laser photocoagulation, gamma knife stereotactic radiosurgery and local surgical resection. More recently Photodynamic Therapy (PDT) is emerging as a promising alternative. As the mechanism of action for PDT is very different to each of these three therapies, the potential for enhanced efficacy with any of these combinations is available. Photodynamic Therapy (PDT) is a treatment modality involving three components; a photosensitiser (PS), light and molecular oxygen. These agents are non-toxic alone, but when combined trigger reactive-oxygen species (ROS) generation resulting in oxidative stress and cytotoxicity. PDT is beneficial in reducing the occurrence of tumour resistance as multiple forms of ROS are produced simultaneously. The main problem with PDT is getting the light to the appropriate depth of penetration, with melanoma in particular difficult to penetrate.

This research proposes a novel formulation of a combination therapy for ocular melanoma to include a photosensitising (PS) agent alongside a targeting antimicrobial peptide (AMP) encapsulated within a nanoparticle for enhanced delivery.  The applicants have previously shown Rose Bengal (RB) to be an efficient PS for use in PDT, an efficacy that can be further enhanced by specific cell targeting. As a result of cellular heterogeneity in tumours, AMPs have emerged as a novel means of enabling transmembrane delivery of active agents.  We intend to exploit them in order to provide targeted delivery of the AMP conjugated to RB.  Because of tumour immune suppression, we will also exploit novel immunotherapeutics in combination with our PDT-based approach. Finally, with the use of nanotechnologies, this research will investigate the ability to deliver this enhanced treatment therapy as a topical suspension for ocular delivery. If successful we would be broadening the treatment options for patients with melanoma by providing both targeted neoadjuvant and adjuvant options.

Overall Aim: Develop the potential of PDT and other targeted synergistic therapies for the adjuvant and neoadjuvant treatment of ocular melanoma (OM) using nano/micro particles for enhanced delivery. Specific Aim 1: Establish the efficacy of RB-(KLAKLAK)2 conjugate and daylight PDT in OM cells. Specific aim 2: Investigate the potential of synergistic effect by combining PDT with chemo- and immunotherapies for concomitant delivery. Specific Aim 3: Formulation of therapies into a suitable drug delivery system and subsequent cellular uptake studies. Specific Aim 4: Utilising an ex-vivo ocular model to establish the effectiveness of the drug delivery system.


Essential criteria

  • To hold, or expect to achieve by 15 August, an Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC) in a related or cognate field.
  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • First Class Honours (1st) Degree
  • Masters at 65%
  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Research project completion within taught Masters degree or MRES
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings

Funding

    The University offers the following awards to support PhD study and applications are invited from UK, EU and overseas for the following levels of support:

    Vice Chancellors Research Studentship (VCRS)

    Full award (full-time PhD fees + DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £15,000 maintenance grant 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.

    Vice-Chancellor’s Research Bursary (VCRB)

    Part award (full-time PhD fees + 50% DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £7,500 maintenance grant 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.

    Vice-Chancellor’s Research Fees Bursary (VCRFB)

    Fees only award (PhD fees + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees 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.

    Department for the Economy (DFE)

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 15,009 per annum for three years. EU applicants will only be eligible for the fee’s component of the studentship (no maintenance award is provided). For Non-EU nationals the candidate must be "settled" in the UK. 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.

    Due consideration should be given to financing your studies; for further information on cost of living etc. please refer to: www.ulster.ac.uk/doctoralcollege/postgraduate-research/fees-and-funding/financing-your-studies


Other information


The Doctoral College at Ulster University


Reviews

Profile picture of Kieran O'Donnell

My experience has been great and the people that I have worked with have been amazing

Kieran O'Donnell - 3D printing of biological cells for tissue engineering applications

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Profile picture of Michelle Clements Clements

Completing the MRes provided me with a lot of different skills, particularly in research methods and lab skills.

Michelle Clements Clements - MRes - Life and Health Sciences

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Profile picture of William Crowe

Throughout my PhD I’ve been provided with continuous support and guidance by my supervisors and the staff at the University.I’ve also received many opportunities to further enhance my professional development in the form of teaching experience and presenting my work at conferences which will aid in my pursuit of a career in academia or industry.

William Crowe