About the Project
This position will be primarily based in the Balasubramanian lab in the Department of Chemistry, University of Cambridge.
We seek an enthusiastic PhD student to work on one of our two primary research areas. The first focuses on the formation and dynamics of G-quadruplex secondary structures in the genome (DNA) and transcriptome (RNA) to understand their functions in mechanisms, ranging from gene expression and RNA biology to DNA replication and genome stability in normal and cancer cells. We use chemical biology approaches that integrate chemistry and molecular genomics with the aim of ultimately exploiting G-quadruplexes as biomarkers of disease, and as therapeutic targets for future drug development (e.g. Nature Reviews Molecular Cell Biology, 2017, 18, 279-284). The second area investigates chemical modifications of nucleic acid bases (the expanded DNA alphabet). The project explores the dynamics and function of natural, chemically-modified DNA bases, as potential epigenetic features. We have developed chemical techniques to detect and sequence cytosine modifications at single base resolution (Science 2012, 336, 934-937; Nature Chemistry 2014, 6, 435-440). We also use isotope labelling with high sensitivity liquid chromatography-mass spectrometry, to explore the dynamics and functions of base modifications during development and in cancer (e.g. Nature Chemistry 2014, 6, 1049-1055; Nature Chemical Biology 2015, 11, 555-557). We are extending our approaches to identify and elucidate the roles of newly discovered base modifications (e.g. Genome Biology 2017, 18:23; J.Am.Chem.Soc. 2017, 139, 1766-1769), the enzymes that control their formation, and also to discover other natural base modifications that are part of the natural expanded DNA alphabet.
Funding Notes
The studentships provide a maintenance grant and tuition fees at the UK/EU rate. Non-EU nationals will be considered only if they can cover the differential for overseas tuition fees.
Applicants must have (or expect to obtain) at least the equivalent of a UK upper second class honours degree (and preferably a Masters) 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.
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