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Funded PhD Opportunity

Engineering plasmid nanoparticles as a platform for delivery of therapeutics

Subject: Biomedical Sciences


Summary

Background Plasmids have been used to deliver therapeutics in the form of peptides and proteins. As with any other DNA therapeutic, they have low toxicity and are easy to manufacture, store and transport. DNA therapeutics have demonstrated no dose limiting toxicity and do not stimulate production of neutralising antibodies. Thus they can be safely administered repeatedly to achieve a therapeutic endpoint. Unfortunately the uptake of naked DNA plasmids tends to be poor, and they can be rapidly degraded by nucleases in vivo.

Underlying aim

This project seeks to explore the potential of nanosize assembled plasmids as active delivery agents of peptides and proteins. More particularly, the project will explore the potential of assembling double stranded DNA of plasmids into nanostructures with optimized dimensions functionalized for targeted uptake by cells, or tissues for the production of encoded peptides or/and proteins.

Specific objectives/Methodology

1.Design of nanoplasmids. Several designs of nanoplasmids will be performed using currently available software (e.g. CadNano). For proof of concept the designs will be enabled on a plasmid coding for a fluorescent protein. It will also be labelled with fluorescent tags for assessing tissue delivery and intracellular fate.

2.Engineering of nanoplasmids. Common DNA nanotechnology self-assembly strategies will be utilized to engineer the nanostructures, and improve the yields of the nanoplasmid self-assembly.

3.Nanoplasmid characterisation. Characterisation will involve determining the morphology and dimensions utilizing AFM, as well as response to enzymatic degradation.

4.Functionality of nanoplasmid. Tissue culture will be used to evaluate cell targeting, triggering and functionality, of intracellularly delivered nanoplasmids utilizing cell imaging.

5.Target delivery of nanoplasmids. Biodistribution, fate, and triggering of expression of the nanoplasmids will be examined using whole body imaging of animal models.

Requisite experience Applicants will be expected to have cell culture and animal work experience.

References

1.Folding DNA to create nanoscale shapes and patterns. Rothemund PWK. Nature 440(2006)297-302.

2.Encoding DNA quadruplex structure. Dvorkin et al. Science Advances 4(2018)eaat3007.

3.Development of a DNA vaccine targeting human papillomavirus type 16 oncoprotein E6. Peng SW et al. Journal of Virology 16(2004) 8468-8476.

4.Room-temperature and selective triggering of supramolecular assembly-disassembly by non-ionizing radiation. Greschner A.A et al. Journal of the American Chemical Society 141(2019)3456-3469.


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 Mateus Webba Da Silva


Other supervisors

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