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Single Molecule studies of CRISPR/Cas9 activities during DNA break repair

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  • Full or part time
    Prof Rueda
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Department Name:
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London

Supervisors:
Professor David Rueda (Imperial)
Dr Benjamin Taylor (AZ)
Dr Emanuela Cuomo (AZ)

The CRISPR/Cas9 nuclease generates a double-strand DNA break at a site dictated by 20 nucleotides coded within a co-associated RNA molecule. Cas9 is now widely used for rapid and cost effective genome engineering. There is still a paucity of knowledge in the molecular details of its mechanism of action in mammalian cells. Using advanced single molecule microscopy and cellular genome engineering techniques, this studentship will define the biochemical and biophysical activity of the Cas9 protein-RNA complex life cycle.

The PhD position is a CASE studentship based at MRC Clinical Sciences Centre, Imperial College London for 4 years . The project is a scientific collaboration between a team at Imperial College and a team at AstraZeneca and the successful applicant will also spend time at the AstraZeneca site in Cambridge as necessary for progression of the project.

Applications

Applicants must hold, or expect to obtain, a first or upper second-class honours degree or equivalent in an appropriate subject from a recognised academic institution. To apply, click on EMAIL NOW sending your CV, the names and addresses of at least two academic referees and a personal statement of no more than 1,000 words explaining your interest in the project.

Please assume that your application has not been successful if you have not heard from us within a month of the closing date.

Funding Notes

BBSRC funding is available for UK nationals and EU students who meet the residency requirements. Further information about eligibility for funding can be found on the BBSRC website:
http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/

References

Senavirathne, G., Jaszczur, M., Auerbach, P. A., Upton, T. G., Chelico, L., Goodman, M. F., & Rueda, D. (2012). Single-stranded DNA Scanning and Deamination by APOBEC3G Cytidine Deaminase at Single Molecule Resolution. Journal of Biological Chemistry, 287(19), 15826–15835. doi:10.1074/jbc.M112.342790
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012). A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science. doi:10.1126/science.1225829
Mali, P., Aach, J., Stranges, P. B., Esvelt, K. M., Moosburner, M., Kosuri, S., … Church, G. M. (2013). CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nature Biotechnology, 31(9), 833–8. doi:10.1038/nbt.2675
Sternberg, S. H., Redding, S., Jinek, M., Greene, E. C., & Doudna, J. a. (2014). DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature, 507(7490), 62–7. doi:10.1038/nature13011
Knight, S. C., Xie, L., Deng, W., Guglielmi, B., Witkowsky, L. B., Bosanac, L., … Tjian, R. (2015). Dynamics of CRISPR-Cas9 genome interrogation in living cells. Science, 350(6262), 823–826. doi:10.1126/science.aac6572

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