PhD Positions

PhD Studentship: Chemical Biology of the Genome and the Epigenome

Based at Yusuf Hamied Department of Chemistry

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 (http://www.balasubramanian.co.uk).  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 Biology2017, 18, 279; Nature Chemistry2017, 9, 1110; Nature Genetics, 2016, 48, 1267; Nature Communications20178, 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 Chemistry2017, 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.

Funding

The studentship provides tuition and college fees and a maintenance grant at the UK rate.

Non-UK applicants will only be considered if they are able to fund the overseas fees differential or if they are awarded a suitable scholarship.

To apply, please email a cover letter, CV, detailed academic transcripts and the contact details for at least two academic referees to:  Jo Lockhart, Balasubramanian Group Science Administrator (email: BalasubramanianRecruitment@ch.cam.ac.uk), including ‘PhD – Chemistry’ in the subject.

Your cover letter should explain why you wish to be considered for the studentship and describe the qualities and experience you will bring to the role. Please also state how you learned of the studentship.

 

You will also need to apply using the University Applicant Portal. For further information about the course and to access the applicant portal, go to:   https://www.postgraduate.study.cam.ac.uk/courses/directory/pcchpdpch

Please select to commence study in Michaelmas term 2022 (October 2022).

Deadline The closing date for applications is 30 November 2021

PhD Studentship: Epigenetic Features of the Genome

Based at CRUK Cambridge Institute

The state-of-the-art Cancer Research UK Cambridge Institute is a joint venture between Cancer Research UK and the University of Cambridge, researching basic cancer and computational biology through to translational research and clinical application. Graduate students play a pivotal role in the continuing success of our research programmes and the Institute affords an excellent opportunity to start a research career in an environment committed to training outstanding cancer research scientists of the future. Professor Sir Shankar Balasubramanian is seeking a student to work on the Epigenetic Features of the Genome. This position will be primarily based in the Balasubramanian lab in the CRUK Cambridge Institute and is likely to involve collaborative interactions with the group’s sister lab in the Yusuf Hamied Department of Chemistry, in Cambridge.

Project details

The lab exploits both chemistry and biology to address fundamental mechanisms of genome function (http://www-balasubramanian.ch.cam.ac.uk).  While many genetic determinants of cancer are known, alternative nucleic acid secondary structures and chemically modified DNA (or RNA) bases can be epigenetic features of nucleic acids that are important to normal biology and in oncogenesis. The project will explore chemical modifications as epigenetic features and how these influence secondary structure formation and function in the genome of normal and cancer cells. The scope of the project may include exploring the formation and dynamics of G-quadruplex structures and modified DNA bases in the genome and their roles in gene expression, DNA replication and genome stability. We have developed methods to show that G-quadruplexes are enriched in cancer-related genes and have a profound impact on transcription (e.g., Nature Genetics 52, 878, 2020; Nature Biotechnology 33, 877, 2015; Genome Biology 22, 117, 2021, 22, 143, 2021). We have also developed genome-wide mapping and sequencing of modified bases and are now exploring further base modifications (e.g., Genome Biology 18, 23, 2017; Nature Chemical Biology 11, 555, 2015).

Preferred skills/knowledge

The student will be highly motivated, capable of independent thought and have excellent communication skills with the ability to work collaboratively.  Ideally, the candidate will have a strong background in molecular biology and/or biochemistry.  A good knowledge of genomics and the chemistry/chemical biology of nucleic acids is highly desirable.

Funding

This studentship is funded by Cancer Research UK and includes full funding for University and College fees and in addition, a stipend of £19,000 per annum, for 4 years.

Eligibility

No nationality restrictions apply to Cancer Research UK funded studentships.  Applications are invited from recent graduates or final year undergraduates who hold or expect to gain a first/upper second-class degree (or equivalent) in a relevant subject from any recognised university worldwide.

How to apply

Please send your academic CV and a covering letter as attachments to Jo Lockhart, Balasubramanian Group Science Administrator, (BalasubramanianRecruitment@ch.cam.ac.uk), including ‘PhD – CI’ in the subject.

Your CV should include the names and contact details of two academic referees who have agreed to act on your behalf, a list of the examinations taken at undergraduate level and if possible, your examination results.

Your cover letter should explain why you wish to be considered for the studentship and describe the qualities and experience you will bring to the role. Please also state how you learned of the studentship.

For queries regarding the post, please contact Jo Lockhart at BalasubramanianRecruitment@ch.cam.ac.uk.

You will also need to apply using the University Applicant Portal. For further information about the course and to access the applicant portal, go to:   https://www.graduate.study.cam.ac.uk/courses/directory/cvcrpdmsc

Please select to commence study in Michaelmas term 2022 (October 2022).

To complete your on-line application, you need to provide the following:

Reference Request: The names and contact details of two academic referees who have agreed to act on your behalf.

Course Specific Question: Your statement of interest (limit of 2,500 characters) should explain why you wish to be considered for the studentship and which qualities and experience you will bring to the role. Please also state how you learned of the studentship.

Supporting Document: Please upload your CV (PDF file), which should include a list of the examinations taken at undergraduate level and if possible, your examination results

Deadline The closing date for applications is 30 November 2021.

For queries, please contact Jo Lockhart at BalasubramanianRecruitment@ch.cam.ac.uk.