What other shapes can DNA form in cells?


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, how and when they may form in the genome. Potentially, targeting these alternative DNA structures could allow for specific interventions and therapeutics for genetic diseases such as cancer or diabetes.

Imagine being able to have an indication of the types of DNA/RNA secondary structure present at any one time in an organism. This PhD project will involve developing chemical probing methods to reveal the structure of DNA in cells on a genome wide scale. The project will be highly interdisciplinary and will involve training in a wide range of techniques: bioinformatic analysis of where alternative DNA structures are in the genome; identifying alternative DNA structures using biophysical techniques and cell biology and molecular biology methods to develop new techniques to identify alternative DNA structures in cells. Led by Dr Zoë Waller and Dr Yiliang Ding, there will be the opportunity to work using different facilities in the school of Pharmacy at UEA, the John Innes Centre and also 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.

Informal enquiries are welcomed: please contact Dr Zoë Waller (z.waller@uea.ac.uk) or Dr Yiliang Ding (yiliang.ding@jic.ac.uk).

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