Think you know the structure of DNA? Think again. It is often assumed that DNA exists only as the iconic Watson-Crick “twisted ladder” double helix; but it can actually adopt many different types of structures. These “alternative” structures may play a role in gene expression (whether genes are switched on or off) and also in the development and progression of genetic diseases.
Compared to the classical double helix, far less is known about these structures and how proteins interact with them. Do they bind and stabilise these structures or do they unfold them? Potentially, targeting these DNA-protein interactions could allow for specific interventions and therapeutics for genetic diseases.
This PhD project will involve investigating naturally occurring proteins which bind these alternative DNA structures. The project will be highly interdisciplinary and will involve training in a wide range of techniques, from expressing and purifying proteins, to characterisation of their interaction with DNA and where they bind in the human genome. Led by Dr Zoë Waller and Dr Andrew Gates, there will be the opportunity to work using different facilities in the schools of Pharmacy and Biological Sciences and also further in the Norwich Research Park.
The student will have, or expect to obtain a first class, 2(i) or equivalent Honours degree in Chemistry, Biochemistry, Pharmacy or a related area.
i) Brooks, TA; Kendrick, S; Hurley, L; Making sense of G-quadruplex and i-motif functions in oncogene promoters FEBS J. 2010, 277, 3459.
ii) Day, HA; Pavlou, P; Waller, ZAE; i-Motif DNA: structure, stability and targeting with ligands. Bioorg Med Chem. 2014, 15, 4407