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Using synthetic biology to engineer a silver bullet by telling TALEs to kill cancer cells

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  • Full or part time
    Dr Saurin
    Prof Clarke
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Background

Cancer is a genetic disease that is caused by a multitude of different genomic abnormalities. The advent of next generation sequencing means it is now relatively straight forward to identify and catalogue these abnormalities, but the big challenge is to determine which of these are responsible for driving tumour initiation and/or progression. The goal is to then use this information to develop new ways to target cancer cells, by finding tumour-specific targets for the so called “silver bullet”.
The cancer cell genome itself could well represent a perfect target because it is the one thing that separates a tumour cell from any other cell in the body. This PhD will explore whether the genomic fingerprint of a cancer cell can be used as a platform to assemble molecules capable of inducing cell death. This innovative approach will rely on the modification of very recent technologies developed for genome-editing, whereby artificially synthesised proteins (called TALEs) are used to induce a localised cut in the DNA strand. The idea is to re-route the output of TALE-DNA binding from genome-editing to cell death, which would potentially allow selective cell death to be programmed by any small unique genomic sequence.

Techniques

Gene-editing with CRISPR/Cas9 and TALENs
High resolution microscopy
Directed evolution in bacteria
Standard cell and molecular biology methods

See my departmental webpage for further details of the techniques used in the lab (http://medicine.dundee.ac.uk/staff-member/dr-adrian-saurin)

References

Past publications
Nijenhuis W, Vallardi G, Teixeira A, Kops GJ, Saurin AT. Negative feedback at kinetochores underlies a responsive spindle checkpoint signal. Nature Cell Biology. 2014. Dec;16(12):1257-64.

Vallardi G and Saurin AT. Mitotic kinases and phosphatases cooperate to shape the right response. Cell Cycle. 2015;14(6):795-6

Akopyan K, Silva Cascales H, Hukasova E, Saurin AT, Müllers E, Jaiswal H, Hollman DA, Kops GJ, Medema RH, Lindqvist A. Assessing kinetics from fixed cells reveals activation of the mitotic entry network at the s/g2 transition. Molecular Cell. 2014 Mar 6;53(5):843-53. 27

Saurin AT, van der Waal MS, Medema RH, Lens SMA, Kops GJPL. Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis. Nature Communications. 2011 May;.2:316 doi: 10.1038/ncomms1319

*Van der Waal MS, *Saurin AT, Vromans MJ, Vleugel M, Wurzenberger C, Gerlich D Kops GJPL, Lens SMA. Mps1 promotes rapid centromere accumulation of Aurora B. EMBO reports. 2012 Sep;13(9):847-54. *equal contribution

Saurin AT, Durgan J, Cameron AJ, Faisal A, Marber MS, Parker PJ. The regulated assembly of a PKC epsilon complex controls the completion of cytokinesis. Nature Cell Biology. 2008 Aug;10:891-901.

How good is research at University of Dundee in Clinical Medicine?

FTE Category A staff submitted: 49.50

Research output data provided by the Research Excellence Framework (REF)

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