PhD Study : Treatment of Solid Cancerous Tumours using Ultrasound-Targeted-Microbubble-Destruction.

Summary

Ultrasound-targeted-microbubble-destruction is an emerging field in drug delivery and involves the use of low intensity ultrasound to rupture microbubbles at a target site, releasing the attached payloads and encapsulated gas in a localised manner. An additional benefit is that the motion of the microbubbles in the ultrasound field is known to enhance microscale mass transport though impermeable tissue thus assisting payload delivery across the tumour stroma. This project will develop stable drug-carrying microbubble preparations and identify the optimum ultrasound conditions required to enhance drug dispersion and efficacy in tumour spheroids and murine models of pancreatic tumours.

The main objective of this project is to develop a generic microbubble platform for the targeted treatment of solid cancerous tumours that can be used in a neo-adjuvant setting to downstage tumours in advance of surgery or as a palliative therapy to provide improved tumour control with better quality of life.

The project will have 4 specific objectives:

Objective 1: Preparation of Drug-loaded Microbubbles: Avidin-functionalised lipid stabilised microbubbles will be prepared and conjugated to biotinylated drug payloads, available in our laboratory. The MB number, stability and drug/ loading will be determined and an optimised protocol identified.

Objective 2:   Preparation & Characterisation of 3D-tumour spheroids: Although a number of approaches have been explored to prepare spheroids and we have used one such approach to develop these structures in our laboratory, this part of the project will explore a number of alternative methodologies that will exploit the inclusion of polymers to provide more cohesive structures (e.g. methylcellulose, fibrin, laminin, collagen etc.). Methylcellulose attributes a viscosity to media employed in approaches such as the hanging drop methods, but other polymers will be added to see if they can be incorporated into the spheroid extra-cellular matrix. Since our approach will involve the generation of pancreatic tumour spheroids, we will also explore the effects of adding pancreatic stellate cells to our spheroid models since these have been shown to play a significant role in the development of desmoplastic tissues. Initial characterisation will involve an examination of growth characteristics and relating size to cell viability.  Spheroids will also be characterised on the basis of their cohesive nature and histological morphology. Tumour cells will be differentiated from stellate and stellate-derived cells by including pancreatic cells that incorporate marker genes (bioluminescent and fluorogenic) currently in our possession.

Objective 3: Optimisation of ultrasound parameters: The influence of ultrasound parameters together with agents such as microbubbles on dispersion will be determined and optimised.  In the case of conventional cancer chemotherapeutics, the impact of ultrasound parameters on viability will be performed to validate the optimised acoustic properties identified with the fluorogenic surrogates.

Objective 4:  The optimum conditions for maximum dispersion of drug payloads identified in objective 3 will be assessed in mice bearing orthotopic pancreatic tumours

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
• 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
• Sound understanding of subject area as evidenced by a comprehensive research proposal
• Work experience relevant to the proposed project
• Publications - peer-reviewed
• Experience of presentation of research findings
• A comprehensive and articulate personal statement

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