CRISPR and DNA Repair Systems
Group Highlights
CRISPR
Cells must defend their genomes against attack by selfish genetic elements such as viruses. Although CRISPR is widely known as a genome editing technology, the CRISPR system functions as an adaptive immune system in prokaryotes. CRISPR is not synonymous with Cas9, which is an unusual type II system that is rarely present in bacteria. In contrast, type I and type III systems are much more common, and arguably much more interesting. Our lab studies type III CRISPR systems, which confer a complex, multi-layered defence against mobile genetic elements. Detection of viral RNA leads the Cas10 subunit of type III systems to generate the second messenger cyclic oligoadenylate (cOA), which sculpts the cellular response to infection. cOA activates a range of effector proteins which degrade RNA or DNA non-specifically to slow down both viral and host metabolism and “buy some time”. We recently identified and characterised a “Ring nuclease” enzyme, which degrades the cOA signal and returns cells to an uninfected state following viral RNA clearance. Predictably, viruses have evolved countermeasures known as anti-CRISPRs, and we recently discovered a viral anti-CRISPR that circumvents type III CRISPR immunity by rapidly degrades the cOA signalling molecule.
CBASS
CBASS is another prokaryotic defence system that defends against viruses using a wide range of cyclic nucleotide second messengers and effectors. CRISPR and CBASS overlap in the signals and the effectors they use, but CBASS seemly primarily to result in Abortive Infection (or altruistic cell death). We are investigating the mechanism of CBASS systems and the links with cyclic nucleotide signalling more generally in bacterial cells. The hunt is now on for anti-CBASS proteins in viruses!
Our group website: https://crispr.wp.st-andrews.ac.uk/
Group Members
White, Prof Malcolm: [Group PI] Professor
tel: 01334 463432
fax:
room: 307 Annexe
email: [email protected]
Athukoralage, Mr Januka: Postgraduate Student/Demonstrator
tel:
fax:
room:
email: [email protected]
Graham, Dr Shirley: Research Technician Lab Manager
tel: 01334 463419/3436
fax:
room: B313 Annexe
email: [email protected]
Gruschow, Dr Sabine: Research Fellow
tel:
fax:
room:
email: [email protected]
Petrovic-Stojanovska, Mrs Biljana: Research Technician
tel: 01334 463436/3419
fax:
room: Annex Level 3
email: [email protected]
Zhu, Mr Wenlong: Postgraduate Student
tel: 3436
room: Annex
email: [email protected]
Publications
Chapters
Investigation of the cyclic oligoadenylate signaling pathway of type III CRISPR systems
Rouillon, C., Athukoralage, J. S., Graham, S., Grüschow, S. & White, M. F., 1 Jan 2019, Methods in Enzymology. Bailey, S. (ed.). Academic Press/Elsevier , p. 191-218 28 p. (Methods in Enzymology; vol. 616).
Research output: Chapter in Book/Report/Conference proceeding › Chapter
CrRNA biogenesis
Charpentier, E., Van Der Oost, J. & White, M. F., 1 Jan 2013, CRISPR-Cas Systems: RNA-Mediated Adaptive Immunity in Bacteria and Archaea. Springer-Verlag, p. 115-144 30 p.
Research output: Chapter in Book/Report/Conference proceeding › Chapter
Postcards from the Edge: Structural Genomics of Archaeal Viruses
Krupovic, M., White, M. F., Forterre, P. & Prangishvili, D., 2012, Bacteriophages, Part A . Łobocka, M. & Szybalski, W. T. (eds.). San Diego: Elsevier, p. 33-62 30 p. (Advances in Virus Research; vol. 82).
Research output: Chapter in Book/Report/Conference proceeding › Chapter
Archaeal Chromatin Organization
Bell, S. D. & White, M. F., 2010, Bacterial Chromatin. T Dame, R. & Dorman, C. J. (eds.). Springer, p. 205-217
Research output: Chapter in Book/Report/Conference proceeding › Chapter
DNA Repair
White, M. F., 30 Nov 2007, Archaea: Evolution, Physiology, and Molecular Biology. Garrett, R. A. & Klenk, H-P. (eds.). Blackwell, p. 171-183 13 p.
Research output: Chapter in Book/Report/Conference proceeding › Chapter
DNA stability and repair
White, M. F. & Grogan, D. W., 2007, Thermophiles: Biology and Technology at High Temperatures. Robb, F. T., Antranikian, G., Driessen, A. & Grogan, D. W. (eds.). CRC Press
Research output: Chapter in Book/Report/Conference proceeding › Chapter
Articles
CRISPR antiphage defence mediated by the cyclic nucleotide-binding membrane protein Csx23
Grüschow, S., McQuarrie, S., Ackermann, K., McMahon, S., Bode, BE., Gloster, TM. & White, MF., 13 Mar 2024, (E-pub ahead of print) In: Nucleic Acids Research. 15 p., gkae167.
Research output: Contribution to journal › Article › peer-review
Reversible conjugation of a CBASS nucleotide cyclase regulates bacterial immune response to phage infection
Kruger, L., Gaskell-Mew, L., Graham, S., Shirran, S. L., Hertel, R. & White, M., 8 Apr 2024, In: Nature Microbiology.
Research output: Contribution to journal › Article › peer-review
Activation of Csm6 ribonuclease by cyclic nucleotide binding: in an emergency, twist to open
McQuarrie, S., Athukoralage, J. S., McMahon, S. A., Graham, S., Ackermann, K., Bode, B. E., White, M. F. & Gloster, T. M., 27 Oct 2023, In: Nucleic Acids Research. 51, 19, p. 10590-10605 16 p.
Research output: Contribution to journal › Article › peer-review
Antiviral signalling by a cyclic nucleotide activated CRISPR protease
Rouillon, C. M. J., Schneberger, N., Chi, H., Blumenstock, K., Da Vela, S., Ackermann, K., Moecking, J., Peter, M. F., Boenigk, W., Seifert, R., Bode, B. E., Schmid-Burgk, J. L., Svergun, D., Geyer, M., White, M. & Hageluken, G., 2 Feb 2023, In: Nature. 614, p. 168–174
Research output: Contribution to journal › Article › peer-review
Antiviral type III CRISPR signalling via conjugation of ATP and SAM
Chi, H., Hoikkala, V. P., Gruschow, S., Graham, S., Shirran, S. L. & White, M., 26 Oct 2023, In: Nature. 622, 7984, p. 826-833 22 p.
Research output: Contribution to journal › Article › peer-review
Repurposing the atypical Type I-G CRISPR system for bacterial genome engineering
Shangguan, Q. & White, M., 1 Aug 2023, In: Microbiology. 169, 8, 9 p., 001373.
Research output: Contribution to journal › Article › peer-review
Structure of the Saccharolobus solfataricus type III-D CRISPR effector
Cannone, G., Kompaniiets, D., Graham, S., White, M. & Spagnolo, L., 20 Feb 2023, In: Current Research in Structural Biology. 5, 8 p., 100098.
Research output: Contribution to journal › Article › peer-review
Cyclic nucleotide signaling in phage defense and counter-defense
Athukoralage, J. S. & White, M. F., Sept 2022, In: Annual Review of Virology. 9, p. 451-468 18 p.
Research output: Contribution to journal › Article › peer-review
Cyclic nucleotide-induced helical structure activates a TIR immune effector
Hogrel, G., Guild, A., Graham, S., Rickman, H., Grüschow, S., Bertrand, Q., Spagnolo, L. & White, M. F., 25 Aug 2022, In: Nature. 608, 7924, p. 808–812 5 p.
Research output: Contribution to journal › Article › peer-review
Structure and mechanism of the type I-G CRISPR effector
Shangguan, Q., Graham, S., Sundaramoorthy, R. & White, M. F., 28 Oct 2022, In: Nucleic Acids Research. 50, 19, p. 11214-11228 15 p.
Research output: Contribution to journal › Article › peer-review
Other publications
Author Correction: Cyclic nucleotide-induced helical structure activates a TIR immune effector (Nature, (2022), 608, 7924, (808-812), 10.1038/s41586-022-05070-9)
Hogrel, G., Guild, A., Graham, S., Rickman, H., Grüschow, S., Bertrand, Q., Spagnolo, L. & White, M. F., 2 Feb 2023, In: Nature. 614, 7946, p. E15
Research output: Contribution to journal › Comment/debate › peer-review
Life Sciences New Talent collection
Pritchard, C., White, M. F. & Brown, S., 2022, In: Royal Society Open Science. 9, 1, 211981.
Research output: Contribution to journal › Editorial › peer-review
Cpf1 shape -shiftsfor streamlined CRISPR cleavage
White, M. F., May 2016, In: Nature Structural and Molecular Biology. 23, 5, p. 365-366 2 p.
Research output: Contribution to journal › Editorial › peer-review
Cpf1 shape-shifts for streamlined CRISPR cleavage
White, M. F., 4 May 2016, In: Nature Structural and Molecular Biology. 23, 5, p. 365-6 2 p.
Research output: Contribution to journal › Editorial
Structure and mechanism of the CRISPR associated complex for antiviral defense (CASCADE)
Lawrence, C. M., Lintner, N. G., Kerou, M. & White, M. F., Apr 2012, In: FASEB Journal. 26, 1 p.
Research output: Contribution to journal › Abstract › peer-review
Recognition of Archaeal CRISPR RNA: No P in the alindromic Repeat?
Lawrence, C. M. & White, M. F., 9 Feb 2011, In: Structure. 19, 2, p. 142-144 3 p.
Research output: Contribution to journal › Editorial › peer-review
DNA Damage: from Causes to Cures
Bowater, R. P., Borts, R. H. & White, M. F., Jun 2009, In: Biochemical Society Transactions. 37, p. 479-481 3 p.
Research output: Contribution to journal › Editorial › peer-review
Recombination Machinery: Holliday junction resolving enzymes
White, M. F., 2004
Research output: Other contribution
Archaeal DNA repair: paradigms and puzzles
White, M. F., Jun 2003
Research output: Other contribution
Transcriptional response to DNA damage in the archaeon Sulfolobus solfataricus
Salerno, V., Napoli, A., White, M. F., Rossi, M. & Ciaramella, M., 1 Nov 2003
Research output: Other contribution
Contact
Join Us
Postdoc positions will be advertised here and on the website jobs.ac.uk when available. If you are interested in the possibility of bringing your own fellowship to our lab, so much the better!
PhD recruitment begins in Oct-Dec with advertisement on FindaPhD.com.
There is specific funding available for Chinese nationals to undertake a PhD in our lab; more details here.
Please get in touch ([email protected]) for further information
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