PhD Study : Stimuli-responsive DNA-based nanodevices

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Summary

Background

DNA is an attractive polymer building material for nanodevices due to its ability for self-recognition and self-assembly. These nanodevices are highly programmable, can be made stimuli-responsive (pH-, and photo-responsive), and allow functionalization with multiple entities such as imaging modalities (fluorophores), targeting entities (aptamers), and drug conjugation (chemical linkers). Their assembly relies on the formation of base-specific interactions that allow strands to adopt structures in a controllable fashion. Most DNA-based higher order structures are based on DNA double helices stabilized by Watson− Crick complementarity. A number of nonclassical pairing patterns are also possible resulting in formation of unusual structures that include, G-quadruplexes, i-motifs, triplexes, and parallel-stranded duplexes. Some of these DNA-based building blocks have advantages over conventional duplex DNA, such as enhanced resistance to degradation enzymes, thermal stability and sensitivity to chemical stimuli.

Underlying aim

This project seeks to explore the potential of nanosize assembled DNA architectures for diagnostic and therapeutic purposes. Some obstacles exist for clinical translation of these devices that target cytoplasm. A major one is that DNA nanostructures tend to be trapped and degraded in lysosomes, preventing their application for therapeutic targeting of cell nuclei or cytoplasm. Approaches to address this issue will be explored.

In this project two main types of devices will be exploited: Stimuli-responsive sensor devices (pH-responsive, photoswitchable, aptamer-based) Nanoplasmids for targeted delivery of functional immune responsive peptides/proteins.

Requisite experience

Candidates with degrees in Biomedical Sciences, Pharmacy, Chemistry, or related sciences with keen interest in learning new techniques.

Please note: Applications for more than one PhD studentships are welcome, however if you apply for more than one PhD project within Biomedical Sciences, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission. If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a PhD studentship. In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.

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
  • Clearly defined research proposal detailing background, research questions, aims and methodology

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

Recommended reading

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

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

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

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.

Aptamer-Programmed DNA Nanodevices for Advanced, Targeted Cancer Theranostics, Walia et al.Acs Applied Bio Materials 4 (2021) 5392-5404.

A DNA nanodevice-based vaccine for cancer immunotherapy, Liu et al. Nature Materials 20(2021)421

The Doctoral College at Ulster University

Key dates

Submission deadline
Monday 28 February 2022
12:00AM

Interview Date
April 2022

Preferred student start date
mid September 2022

Applying

Apply Online  

Contact supervisor

Dr Mateus Webba Da Silva

Other supervisors