An iCASE studentship (with enhanced stipend) is available to develop and apply state-of-the-art single molecule imaging and manipulation techniques to study the molecular basis of DNA Repair.
DNA-protein interactions underpin essential cellular processes such as DNA replication, transcription, and repair, and proteins involved in these processes are targeted in a variety of cancer therapies. Many structures of damaged DNA-protein complexes reveal stark bends in the DNA substrate, suggesting that proteins may exert force on the DNA to bend it during recognition of the damage site, or for catalytic enhancement of the repair.
Here you will develop novel instrumentation to investigate how force modulates the DNA-protein interactions involved in DNA repair, and establish high-throughput screening methods which mimic physiological forces on DNA substrates. These forces naturally arise in cells due to transcription and DNA packaging, and will improve hit identification for repair inhibitors, advancing the emerging field of mechanopharmacology.
Objectives:
(1) Design and build a combined magnetic tweezer-single molecule fluorescence microscope in collaboration with Cairn Research.
(2) Use the new instrument to investigate the effect of forces on DNA-protein interactions and DNA damage recognition.
(3) Implement a high-throughput version of the assay to screen protein-DNA interactions under physiological forces.
You will be part of a new multidisciplinary collaboration between Dr. Tim Craggs (Dept. of Chemistry www.craggs-lab.com), Dr. Chris Toseland (Dept. of Oncology and Metabolism www.toseland-lab.com), Prof. Ashley Cadby (Dept. of Physics and Astronomy) and Cairn Research (www.cairn-research.co.uk). You will receive excellent training in developing novel instruments and assays to study DNA-protein interactions, including a fully funded 3 months spent at Cairn Research, working directly with instrument engineers.
You will join a collaborative, supportive research community in Sheffield, with world-leading single molecule and nucleic acid research centres (http://www.imagine-imaginglife.com and www.genome.sheffield.ac.uk) and an active, friendly and lively PhD student cohort, which hosts regular social events alongside networking and career development opportunities. We are committed to supporting the career development of our students, encouraging attendance at both international and UK conferences and training courses to develop your research skills and interests.
Given the interdisciplinary nature of the role, we encourage applications from a diverse range of scientific backgrounds e.g. biophysics, physics, and biochemistry. Motivated individuals from all backgrounds will receive all the necessary training to excel in this project.
Interested applicants should contact Tim Craggs or Chris Toseland to discuss the project: [Email Address Removed] or [Email Address Removed]
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme and how to apply can be found on our website:
https://bit.ly/3lQXR8A
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