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*EASTBIO* Harnessing the CRISPR system of the human pathogen Mycobacterium tuberculosis

  • Full or part time
    Prof M F White
  • Application Deadline
    Sunday, January 05, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

BBSRC Thematic Group: Frontier Bioscience
CRISPR is a prokaryotic adaptive immune system that has been harnessed for a wide range of genome engineering, synthetic biology, biotechnology and healthcare applications. This project will focus on the CRISPR system of the important human pathogen Mycobacterium tuberculosis (Mtb), the causative agent of TB. Mtb has a Type III CRISPR system which is more complex than Cas9, consisting of a large ribonucleoprotein machine that detects tiny amounts of viral RNA, syntheses a novel cyclic nucleotide second messenger and unleashes an array of defensive enzymes that target and degrade invading genetic entities (1,2). Although this is a powerful immune defence, it must be tightly controlled to avoid killing the host. Many aspects of the Type III CRISPR system remain to be discovered.

In this project, you will focus on the Type III Mtb CRISPR system, which we have expressed and purified for the first time (3). The overall aim will be to develop an understanding of the activities and control of the system that allows it to provide host immunity. For example, we wish to understand how binding of a viral RNA changes the structure of the ribonucleoprotein machine and activates the catalytic domains, using techniques such as single molecule FRET microscopy. By understanding how the CRISPR system is activated, we can manipulate it in vitro to target cellular RNAs, providing a new route to specific control of gene expression. This will involve a collaboration between the White and Penedo labs and will provide opportunities for training in a wide range of cutting-edge technologies including molecular biology, synthetic biology and single molecule biophysics.

You will join a well-funded and friendly lab occupying new, purpose-built lab space in the Biomedical Sciences Research Complex at St Andrews. For more information or informal enquiries, please contact Prof Malcolm White () or Dr Carlos Penedo ().

Funding Notes

This project is eligible for the EASTBIO Doctoral Training Partnership: View Website

This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body.

Apply by 5.00 pm on 5 January 2020 following the instructions on how to apply at: View Website

Please also upload the EASTBO Application Form as an additional document to the University of St Andrews online Application.

Informal inquiries to the primary supervisor are very strongly encouraged.

References

1. Athukoralage, J.S., Rouillon, C., Graham, S., Grüschow, S. and White, M.F. (2018) Ring nucleases deactivate Type III CRISPR ribonucleases by degrading cyclic oligoadenylate. Nature, 562, 277-280.

2. Rouillon, C., Athukoralage, J.S., Graham, S., Grüschow, S. and White, M.F. (2018) Control of cyclic oligoadenylate synthesis in a type III CRISPR system. eLife, 7, e36734.

3. Grüschow, S., Athukoralage, J.S., Graham, S., Hoogeboom, T. and White, M.F. (2019) Cyclic oligoadenylate signalling mediates Mycobacterium tuberculosis CRISPR defence. Nucl. Acids Res., pii: gkz676.

How good is research at University of St Andrews in Biological Sciences?

FTE Category A staff submitted: 50.45

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

Click here to see the results for all UK universities

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