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Investigating the role of DNA structures genetic diseases such as cancer and diabetes (WALLERZU20SF)


Project Description

It is often assumed that DNA exists only as the iconic Watson-Crick double helix but it can actually adopt many different types of structure depending on the sequence and environmental conditions. These alternative structures may play a role in gene expression (whether genes are switched on or off) and also in the development of genetic diseases such as cancer and diabetes. By targeting these alternative DNA structures, this could allow for more specific interventions and therapeutics compared to traditional chemotherapies. It is also indicated that these sequences may play a role in how particular diseases develop and progress.

This PhD project will involve studying these special DNA structures in the genome. Based on our work which discovered multiple sequences in the genome which can form special, four-stranded, i-motif structures. This project will involve characterising the properties of these sequences using biophysical (UV, circular dichroism, NMR spectroscopy) and biological techniques (cell culture, reporter gene and gene expression assays). There will be the opportunity to work and collaborate with other research groups across the Norwich Research Park.

Applicants will have, or expect to obtain a first class, 2(i) or equivalent Honours degree in Chemistry, Biochemistry, Pharmacy, Biology, Natural Sciences or a related area.

Informal enquiries are welcomed; for further information please contact Dr Zoë Waller ()


Project supervisor: http://www.uea.ac.uk/pha/waller

Type of programme: PhD

Start date: October 2020

Mode of study: Full-time

Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at View Website.

A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. Applicants should contact the primary supervisor for further information about the fee associated with the project.

References

i) Balasubramanian, S; Hurley, LH; Neidle, S. Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? Nat Rev Drug Discov. 2011, 10, (4) 261-75.

ii) Brooks, TA; Kendrick, S; Hurley, L; Making sense of G-quadruplex and i-motif functions in oncogene promoters FEBS J. 2010, 277 (17) 3459-69.

iii) Day, HA; Pavlou, P; Waller, ZAE; i-Motif DNA: structure, stability and targeting with ligands. Bioorg Med Chem. 2014, 22 (16) 4407-18.

iv) Wright, EP; Huppert, JL; Waller , ZAE; Identification of multiple genomic DNA sequences which form i-motif structures at neutral pH Nucleic Acids Research, 2017, 45, (6) 2951–2959.

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