Atomic-detail structure of intermediates in self-assembly of G-quadruplex architectures by NMR spectroscopy

Apply and key information  

Summary

Motivation

Biomolecular self-assembly is a topic of current research interest consequent to biological function, therapeutics, biosensor applications, and biotechnological materials. Understanding self-assembly of nucleic acids containing repetitive guanine segments is a current research frontier. These architectures for a variety of architectures with specialized functions in living systems, and the potential for a variety of uses applied to living systems as well as soft materials. Our laboratory has been interested in understanding the control of self-assembly of these architectures known as G-quadruplexes. In our studies we utilize chemical synthesis methods, biomolecular NMR coupled with restrained Molecular Dynamics (MD) simulations for determining the atomic detail structure of these architectures. To understand the mechanism of self-assembly we develop Circular Dichroism (CD) methodology that we employ with MD simulations methods. The knowledge derived is central to understanding and manipulating biological function, as well as uses of these architectures.

Underlying aim

The main objective of this study is to produce novel DNA and RNA atomic-detail architectures representative of intermediates of self-assembly of G-quadruplexes.

Methods to be used

  • Facile chemical synthesis and purification.
  • Biomolecular NMR spectroscopy.
  • Restrained MD simulations.

Impact

The database of architectures developed will be utilized for the development of sensors and therapeutics with collaborators. The trainee will be able to apply biomolecular NMR for the structure determination of nucleic acids and proteins. She/he will be able to determined the atomic detail structure of nucleic acids and proteins.

Candidates with a background in Chemistry, Physics, Engineering, Biomedical Sciences or related sciences preferred.

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
  • 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 record appropriate to career stage
  • Experience of presentation of research findings

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

Funding and eligibility

Recommended reading

  • Scarlett Dvorkin et al Encoding Canonical DNA Quadruplex Structure. Science Advances 4, (2018) eaat3007.
  • Mateus Webba da Silva; (2007) NMR methods for studying quadruplex nucleic acids; Methods, 43, 264-277.
  • Jiri Sponer et al; (2020) Molecular dynamics simulations of G-quadruplexes: The basic principles and their application to folding and ligand binding. Book chapter in QUADRUPLEX NUCLEIC ACIDS AS TARGETS FOR MEDICINAL CHEMISTRY, Series on Annual Reports in Medicinal Chemistry. DOI 10.1016/bs.armc.2020.04.002.
  • Andreas I. Karsisiotis, et al (2011) Topological Characterization of Nucleic Acid G-Quadruplexes by UV Absorption and Circular Dichroism. Angew Chem Int Ed Engl, 50, 10645-10648.
  • Mateus Webba da Silva; (2007) Geometric formalism for DNA quadruplex folding; Chemistry European Journal,13, 9738-9745.

The Doctoral College at Ulster University

Key dates

Submission deadline
Monday 7 April 2025
04:00PM

Interview Date
April 2025

Preferred student start date
15 September 2025

Applying

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Contact supervisor

Dr Mateus Webba Da Silva

Other supervisors