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PhD Studentship: Chemical Biology of the Genome and the Epigenome


Applications are invited for a 4-year PhD studentship in the group led by Professor Sir Shankar Balasubramanian, on a project that is multidisciplinary, exploiting both chemistry and biology to explore fundamental mechanisms of genome function (see http://www-balasubramanian.ch.cam.ac.uk). While the primary genetic code is understood, this project seeks to study alternative nucleic acid secondary structures and/or covalent chemical modifications of DNA bases to understand how they contribute to the function of DNA.

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.

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. The student must be highly motivated, capable of independent thought and have excellent communication skills with the ability to work collaboratively.

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.

Applications should include a cover letter, a CV, detailed academic transcripts and the contact details for at least two academic referees, and should be emailed to: Jo Lockhart, PA to Professor Balasubramanian (email: herchel-smith-medchem-pa@ch.cam.ac.uk), including 'PhD Chemistry' in the subject line. The cover letter should explain why you wish to be considered for the studentship and describe the qualities and experience you would bring to the role. Please also state how you learned of the studentship.

If you wish to be considered for any other available studentships in the Chemistry Department, you must also apply online via the University Applicant Portal and complete the Chemistry Department Application form (further information at http://www.ch.cam.ac.uk/pgapp). Please note that there is an application fee.

Please quote reference MA13141 on your application and in any correspondence about this vacancy. For queries regarding the post, please contact Jo Lockhart at herchel-smith-medchem-pa@ch.cam.ac.uk.