PhD Study : Polymersomes for the delivery of mitochrodrial disrupting peptides and additional combination therapies

Apply and key information  

Summary

Background

Nanotechnology coupled with advanced sophisticated therapies is leading the way for a new generation of chemotherapeutics. Drug delivery systems (DDSs), such as polymersomes (Ps), are capable of encapsulating large amounts of multiple drugs with both hydrophilic and hydrophobic properties simultaneously, as well as offering a mechanism to combat multi drug resistant cancers [1]. However, they could be improved upon by increasing their specificity by active targeting [2].

This research seeks to incorporate mitochrondrial disrupting peptides, which have limited cellular uptake, with Ps to act as carriers to enhance cellular uptake. In addition, alternative therapeutics will be added alongside the peptide to develop a multimodal cocktail of  therapeutic agents with a view to create a potent anticancer therapy, which would be effective against multiple cancer types. Previous research has shown the proapoptotic peptide (KLAKLAK)2 working alongside the photosensitiser Rose Bengal for enhanced efficacy of anticancer photodynamic therapy [3].

This proposal further seeks to explore the potential of various targeting ligands to enhance cytotoxicity of the system

Objective

To synthesis and characterise the peptide (KLAKLAK)2 and derivatives. This peptide will be incorporated within a polymer, before being formulated into a  Ps and loaded with a compound to enable quantification (a chromophore).  Various in-vitro studies will be used to determine the effacy of the DDS with multiple techniques imvestigated to optimise efficacy.

Methods

1. Synthesis and characterisation of the (KLAKLAK)2  peptide and derivatives

2. Formulation and characterisation of polymersomes loaded with chromophore.

3. Pharmacokinetic studies to determine uptake, release and stability of the DDS

4. Cell viability study to establish inherent cytotoxicity of the DDS, culminating in an in-vivo study if successful.

Requisite experience

Applicants will be expected to be familiar with good laboratory practice and cell culture experience will be a benefit.   In vivo experience would be a benefit although specific training in accordance with national requirements will be provided.

References

1.Aibani N, Nesbitt H, Marino N, Jurek J, O’Neill C, Martin C, Di Bari I, Sheng Y, Logan K, Hawthorne S, McHAle AP, Callan JF and Callan B. (2018) Electroneutral polymersomes for combined cancer chemotherapy. Acta Biomaterialia 80, 327-340.

2.Steichen SD, Caldorera-Moore M, Peppas NA. (2013) A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics.  Eur J Pharm Sci 48, 416–427

3.UK Patent Application No. 1707153.1 [information available on request]

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.

  • Sound understanding of subject area as evidenced by a comprehensive research proposal

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.

  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Publications record appropriate to career stage
  • Experience of presentation of research findings
  • A comprehensive and articulate personal statement
  • Use of personal initiative as evidenced by record of work above that normally expected at career stage.
  • Relevant professional qualification and/or a Degree in a Health or Health related area

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

The Doctoral College at Ulster University

Key dates

Submission deadline
Friday 7 February 2020
12:00AM

Interview Date
9 to 20 March 2020

Preferred student start date
Mid September 2020

Applying

Apply Online  

Contact supervisor

Professor Bridgeen Callan

Other supervisors