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  Development of high throughput assay for screening of novel DNA replication inhibitors for therapeutic purposes


   MRC Laboratory of Medical Sciences (LMS)

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  Prof Christian Speck, Prof D Rueda  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

The student will develop a fluorescence-based assay to identify novel DNA replication inhibitors for anti-cancer therapy. Inhibitors will be consequently characterised for their impact on the multi-step DNA replication process and on cancer cell growth. This interdisciplinary project will train the student in biochemistry, biophysics and drug screening.

Cancer is one of the most serious health threats globally and one in two people will develop cancer in their lifetime. Recent progress in our understanding of DNA replication has revealed promising target proteins for inhibitor development. For this project, the successful applicant will combine biophysical, biochemical and structural approaches to develop high-throughput assays that can identify novel DNA replication inhibitors. The student will take advantage of the Speck lab’s expertise in DNA replication, protein engineering and recent advances in reconstituting reactions with purified proteins. Through partners, we have access to several small molecule libraries, which will support the screening process. Moreover, the student will be able to collaborate with group members that investigate the fundamental mechanisms of the DNA replication process or who develop peptides to inhibit specific aspects of DNA replication.

This interdisciplinary project will train the student in protein biochemistry and DNA replication (Speck; Imperial College London, ICS), in detecting structural changes by fluorescence approaches (Rueda; MRC-LMS), in analysing protein-DNA interactions (Di Antonio; Imperial College London, Chemistry) and in drug screening & progression of hits into high quality drug candidates (Fuchter; Imperial College London, Chemistry).

The ideal candidate has a 2.1 degree or better, a background in biophysics, biochemistry and/or chemistry, enjoys to work with proteins and is interested in data analysis and method development.

If you wish to discuss any details of the project informally, please contact Professor Christian Speck ([Email Address Removed]), Imperial College London, Faculty of Medicine.

To apply for this programme please visit the LMS website where the application form is available for download - https://lms.mrc.ac.uk/study-here/phd-studentships/lms-3-5yr-studentships/


Biological Sciences (4)

Funding Notes

This funding covers 3.5 years of UK Home Tuition Fee rates, which includes EU students withexisting pre-settled status.
A stipend amounting to £21000pa is paid directly to the student for 3.5 years total.

References

From structure to mechanism-understanding initiation of DNA replication.
Riera A, Barbon M, Noguchi Y, Reuter LM, Schneider S, Speck C.
Genes Dev. 2017 Jun 1;31(11):1073-1088
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