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Prof M F White, Prof Carlos Penedo
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
BBSRC Theme: World-Class Underpinning 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 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. 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. This will involve a collaboration between the White and Penedo labs in Biology and Physics, and will provide opportunities for training in a wide range of cutting-edge technologies including molecular biology, synthetic biology and single molecule biophysics. In parallel, there are opportunities to manipulate the genome of Mtb using its own CRISPR system, to advance studies of this important pathogen.
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 ([Email Address Removed]) or Dr Carlos Penedo ([Email Address Removed]).
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 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. 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. This will involve a collaboration between the White and Penedo labs in Biology and Physics, and will provide opportunities for training in a wide range of cutting-edge technologies including molecular biology, synthetic biology and single molecule biophysics. In parallel, there are opportunities to manipulate the genome of Mtb using its own CRISPR system, to advance studies of this important pathogen.
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 ([Email Address Removed]) or Dr Carlos Penedo ([Email Address Removed]).
Funding Notes
This project is eligible for the EASTBIO Doctoral Training Partnership: http://www.eastscotbiodtp.ac.uk/
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 December 2018 following the instructions on how to apply at: http://www.eastscotbiodtp.ac.uk/how-apply-0
Informal inquiries to the primary supervisor are very strongly encouraged.
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 December 2018 following the instructions on how to apply at: http://www.eastscotbiodtp.ac.uk/how-apply-0
Informal inquiries to the primary supervisor are very strongly encouraged.
References
Athukoralage, J. S., Rouillon, C., Graham, S., Grüschow, S., & White, M. F. (2018). Ring nucleases deactivate Type III CRISPR ribonucleases by degrading cyclic oligoadenylate. BioRxiv, 380436. doi:https://doi.org/10.1101/380436 (in press at Nature).
Rouillon, C., Athukoralage, J. S., Graham, S., Grüschow, S., & White, M. F. (2018). Control of cyclic oligoadenylate synthesis in a type III CRISPR system. Elife, 7, e36734.
Rouillon, C., Athukoralage, J. S., Graham, S., Grüschow, S., & White, M. F. (2018). Control of cyclic oligoadenylate synthesis in a type III CRISPR system. Elife, 7, e36734.
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