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Funded PhD Opportunity

Development and optimisation of a human in vitro blood brain barrier model for high throughput screening of drug delivery vehicles

Subject: Biomedical Sciences


Summary

Successful delivery of drugs across the blood brain barrier (BBB) is essential for the treatment of numerous neurological conditions. In vitro BBB models are useful for the assessment of drug transport studies as a precursor to preclinical work - due to in part to lower costs, the ability to directly quantify the uptake of compounds and to gain information on their mechanism of action. It is also beneficial to detect potential negative impacts on BBB integrity at an early stage of drug development before commencing in vivo studies. However, the in vitro models developed so far have used animal cell lines and/or cell combinations that do not accurately reflect the architecture of the human BBB in vivo. Recently, we have generated preliminary results on the construction of a human 3D in vitro BBB model which more accurately reflects the in vivo cell architecture. This model shows promise but requires substantial optimisation to produce a robust, reliable assay that may be used for high throughput screening assays. Our pilot studies also suggest that the model can be utilised for the evaluation and quantification of encapsulated drug cargoes across the model.

Underlying aim

To develop and optimise a human cell 3D in vitro BBB assay for the high throughput screening of drug delivery vehicles.

Specific objectives/Methodology

To achieve the underlying aim, the project will be based on the following objectives (OB):

OB1 – develop the preliminary human cell 3D in vitro BBB assay using different human brain cell types including endothelial cells, astocytes and pericytes.

OB2 – optimise the BBB assay using a range of techniques including TEER measurement, SDS PAGE and westen blotting, confocal microscopy and SEM.

OB3 – enhance the BBB assay for high throughput use using a variety 3D scaffolds.

OB4 – develop a range of drug delivery formuations, containing model drugs, based on pegulated polymersomes. Characterisation of these formulations will include size, PDI, zeta potential, encapsulation efficiency and release and stability profiles.

OB5 – testing of these novel drug delivery formualtions on the high throughput BBB assay.

This project will highlight a paradigm shift in the way 3D BBB models are constrcuted, with scope for worldwide implementation and business.

References

Huey, R., O’Hagan, B., McCarron, P. and Hawthorne, S. (2017). International Journal of Pharmaceutics, 525(1), 12-20.

Huey, R., Rathbone, D., McCarron, P. and Hawthorne, S. (2019). Journal of Drug Targeting, 27(9), 959-970.

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) Acta Biomaterialia 80, 327-340.

Martin, C., Marino, N., Curran, C., McHale, A.P., Callan, J.F., Callan, B. (2016). International  Journal of Pharmaceutics. 511, 570 – 579.

Additional Requirements

Desirable experience: nanoparticle formulation and characterization, cell culture, SDS PAGE and western blotting.


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

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

    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


Key dates

Submission deadline
Friday 7 February 2020

Interview Date
9 to 20 March


Applying

Apply Online  


Campus

Coleraine campus

Coleraine campus
The feeling of community at our Coleraine campus makes for a warm and welcoming student experience.


Contact supervisor

Dr Susan Hawthorne


Other supervisors

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