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Applications are invited for a 4-year PhD studentship in the group led by Professor Sir Shankar Balasubramanian, on a multidisciplinary project exploiting both chemistry and biology to explore fundamental mechanisms of genome function ().

We seek a creative and enthusiastic PhD student to work on one of our two primary research goals. The first area is to investigate the structure and function of DNA (and RNA) secondary structures called G-quadruplexes. Studies both in vitro and in cells suggest G-quadruplexes may be important for the control of transcription, translation and other key processes in biology. We employ chemical biology, molecular biophysics, structural biology, cell biology and genomics to explore mechanisms involving G-quadruplexes with an emphasis on intervention strategies for cancer [e.g. see Nature Chemistry 2021, 13, 626-633; Trends in Chemistry, 2020, 2:2, 123-136; eLife, 2019, 8:e46793; Nature, 2018, 558, 465; Nature Reviews Molecular Cell Biology, 2017, 18, 279; Nature Chemistry, 2017, 9, 1110; Nature Genetics, 2016, 48, 1267; Nature Communications, 2017, 8, 14432]. The second area investigates base modifications in nucleic acids. The DNA alphabet also includes natural chemical modifications to DNA bases that can change the structure, recognition and function of DNA. Our research aims to elucidate these modifications and their effects on the folded structure of DNA, protein-DNA interactions and also the assembly of nucleosomes with the goal of explaining how and why this modulates the function of cells and organisms. Examples will include 5-methylcytosine, a well-known epigenetic feature in addition to more-recently discovered modified bases such as 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Our lab employs and develops chemical, physical, biological and genomic approaches to investigate the presence of, and to gain mechanistic insights into modified base function in human, mouse and parasite genomes [e.g. see: Nature Chemistry, 2019, 11, 629; Nature Chemistry, 2018, 10, 1258; Nature Reviews Chemistry, 2017, 1, 0069; Nature Chemical Biology, 2015, 11, 555; Nature Structural & Molecular Biology, 2015, 22, 44; Nature Chemistry, 2014, 6, 1049; Science, 2012, 336, 934].

Applicants must have (or expect to obtain) at least the equivalent of a UK upper second-class Master’s degree in a chemical or biological discipline that is relevant to the project. Ideally, the candidate will have a strong background in organic chemistry and/or chemical biology. A good knowledge of nucleic acid chemistry and/or molecular biology methods is desirable. Motivation, creativity and intellectual independence are desirable, as are excellent communication skills with the ability to work collaboratively.

The studentship commences in October 2022 and provides a maintenance grant and tuition fees at the UK rate. Non-UK applicants will be considered only if they are able to fund the overseas fees differential or if they are awarded a suitable scholarship.

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