Research output per year
Research output per year
Prof
KY16 9ST
United Kingdom
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. We are also interested in developing new diagnostic tools for specific RNA detection by repurposing CRISPR effectors.
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 uses a different signal generator – a nucleotide cyclase ancestral to the human cGAS innate immunity protein. In many cases it is unclear how CBASS systems sense viral infection. We are investigating the mechanism of CBASS systems and the links with cyclic nucleotide signalling more generally in bacterial cells. We are also interested in discovering the mechanisms viruses use to neutralise these defences.
Discovery and molecular understanding of bacterial anti-viral defence systems using a combination of molecular biology, microbiology, biochemistry, bioinformatics and structural biology.
New enzymes for molecular biology. Repurposing CRISPR systems for new diagnostic assays.
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Research output: Contribution to journal › Article › peer-review
Fritzen, R. (Creator), Penedo, C. (Supervisor) & White, M. (Supervisor), University of St Andrews, 4 Feb 2025
DOI: 10.17630/963932fc-cc3e-4b69-b92d-58108e138657
Dataset: Thesis dataset
Chi, H. (Creator) & White, M. (Creator), Protein Data Bank (PDB), 2022
DOI: 10.2210/pdb7qda/pdb, https://doi.org/10.2210/pdb8B0R/pdb and one more link, https://doi.org/10.2210/pdb8B0U/pdb (show fewer)
Dataset
Shangguan, Q. (Creator), Graham, S. (Creator), Sundaramoorthy, R. (Creator) & White, M. (Creator), Protein Data Bank (PDB), 2022
DOI: 10.2210/pdb8ANE/pdb, https://doi.org/10.2210/pdb8B2X/pdb and 2 more links, http://doi.org/doi:10.1093/nar/gkac925, http://doi.org/doi:10.1093/nar/gkac925 (show fewer)
Dataset
Chi, H. (Creator) & White, M. (Creator), Small Angle Scattering Biological Data Bank (SASBDB), 2022
https://www.sasbdb.org/data/SASDQM4 and 3 more links, https://www.sasbdb.org/data/SASDQN4, https://www.sasbdb.org/data/SASDQP4, https://www.sasbdb.org/data/SASDQQ4 (show fewer)
Dataset
Chi, H. (Creator) & White, M. (Creator), GitHub, 2023
https://github.com/vihoikka/Cas10_prober
Dataset: Software
Penedo, C., Annibale, P., Bruce, G. D., Gather, M. C., Guimaraes da Silva, R., Melo Czekster, C., O'Hagan, D., Schwarz-Linek, U., Smith, T. K., Tilsner, J., Varela, J. A. & White, M.
1/08/23 → 31/07/24
Project: Standard
1/11/22 → 31/10/25
Project: Standard
Malcolm F White (Editor)
Activity: Publication peer-review and editorial work types › Editor of research journal
Malcolm White (Speaker)
Activity: Talk or presentation types › Invited talk
Malcolm White (Speaker)
Activity: Talk or presentation types › Invited talk
Malcolm White (Speaker)
Activity: Talk or presentation types › Invited talk
Malcolm White (Speaker)
Activity: Talk or presentation types › Invited talk
White, Malcolm (Recipient), 27 Oct 2010
Prize: Election to learned society
White, Malcolm (Recipient), 2008
Prize: Election to learned society
White, Malcolm (Recipient), 29 Aug 2014
Prize: Prize (including medals and awards)