ORCID Profile
0000-0002-9704-1217
Current Organisation
University of Southampton
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Publisher: Oxford University Press (OUP)
Date: 04-10-2021
DOI: 10.1093/NAR/GKAB883
Abstract: To provide protection against viral infection and limit the uptake of mobile genetic elements, bacteria and archaea have evolved many erse defence systems. The discovery and application of CRISPR-Cas adaptive immune systems has spurred recent interest in the identification and classification of new types of defence systems. Many new defence systems have recently been reported but there is a lack of accessible tools available to identify homologs of these systems in different genomes. Here, we report the Prokaryotic Antiviral Defence LOCator (PADLOC), a flexible and scalable open-source tool for defence system identification. With PADLOC, defence system genes are identified using HMM-based homologue searches, followed by validation of system completeness using gene presence/absence and synteny criteria specified by customisable system classifications. We show that PADLOC identifies defence systems with high accuracy and sensitivity. Our modular approach to organising the HMMs and system classifications allows additional defence systems to be easily integrated into the PADLOC database. To demonstrate application of PADLOC to biological questions, we used PADLOC to identify six new subtypes of known defence systems and a putative novel defence system comprised of a helicase, methylase and ATPase. PADLOC is available as a standalone package (adlocbio adloc) and as a webserver (padloc.otago.ac.nz).
Publisher: Public Library of Science (PLoS)
Date: 20-07-2012
Publisher: Cold Spring Harbor Laboratory
Date: 26-01-2019
DOI: 10.1101/527796
Abstract: Microbiomes are vast communities of microbes and viruses that populate all natural ecosystems. Viruses have been considered the most variable component of microbiomes, as supported by virome surveys and ex les of high genomic mosaicism. However, recent evidence suggests that the human gut virome is remarkably stable compared to other environments. Here we investigate the origin, evolution, and epidemiology of crAssphage, a widespread human gut virus. Through a global collaboratory, we obtained DNA sequences of crAssphage from over one-third of the world's countries, and showed that its phylogeography is locally clustered within countries, cities, and in iduals. We also found colinear crAssphage-like genomes in both Old-World and New-World primates, challenging genomic mosaicism and suggesting that the association of crAssphage with primates may be millions of years old. We conclude that crAssphage is a benign globetrotter virus that may have co-evolved with the human lineage and an integral part of the normal human gut virome.
Publisher: Springer Science and Business Media LLC
Date: 04-06-2012
DOI: 10.1007/S10158-012-0136-7
Abstract: Acute and chronic exposure of Caenorhabditis elegans to concentrations of ethanol in the range 250-350 mM elicits distinct behaviours. Previous genetic analysis highlights specific neurobiological substrates for these effects. However, ethanol may also elicit cellular stress responses which may contribute to the repertoire of ethanol-induced behaviours. Here, we have studied the effect of ethanol on an important arm of the cellular stress pathways, which emanates from the endoplasmic reticulum (ER) in response to several conditions including heat shock and chemical or genetic perturbations that lead to protein misfolding. HSP-4 is a heat shock protein and homologue of mammalian BiP. It is a pivotal upstream component of the ER stress response. Therefore, we used a C. elegans heat shock protein mutant, hsp-4, and a strain carrying a transcriptional reporter, Phsp-4::gfp, to test the role of the ER following chronic ethanol conditioning. We found no evidence for an overt ER response during acute or prolonged exposure to concentrations of ethanol that lead to defined ethanol-induced behaviours. Furthermore, whilst hsp-4 was strongly induced by tunicamycin, pre-exposure of C. elegans to low doses of tunicamycin followed by ethanol was not sufficient to induce an additive ER stress response. Behavioural analysis of an hsp-4 mutant indicated no difference compared to wild type in susceptibility to ethanol intoxication and withdrawal. There is a clear precedent for a significance of ER stress pathways particularly in clinical conditions associated with toxic or pathological effects of high doses of alcohol consumption. The concentrations of ethanol used in this C. elegans study equate to the highest blood alcohol levels measured in patients with chronic alcohol dependency. Taken together, these observations imply that the classic ER stress pathway in C. elegans is relatively refractory to induction by ethanol.
Publisher: Elsevier BV
Date: 06-2015
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 17-03-2011
Location: United Kingdom of Great Britain and Northern Ireland
Location: Netherlands
No related grants have been discovered for Lindy Holden-Dye.