A5056751974- Enzyme Structure and Function
- SARS-CoV-2 and COVID-19 Research
- Microbial Metabolism and Applications
- Genomics and Phylogenetic Studies
- Cancer Research and Treatments
- COVID-19 Clinical Research Studies
- Enzyme Production and Characterization
- Animal Virus Infections Studies
- Viral Infections and Vectors
- Hepatitis C virus research
- Amino Acid Enzymes and Metabolism
- Biochemical and Molecular Research
- COVID-19 epidemiological studies
- SARS-CoV-2 detection and testing
- Ubiquitin and proteasome pathways
- Molecular Biology Techniques and Applications
- Mosquito-borne diseases and control
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- RNA modifications and cancer
- Genetics, Bioinformatics, and Biomedical Research
- Insect symbiosis and bacterial influences
- Herpesvirus Infections and Treatments
MRC University of Glasgow Centre for Virus Research
2012-2024
Medical Research Council
2022-2024
University of California, Irvine
2024
Beijing University of Technology
2024
Illumina (United States)
2022
Imperial College London
2020
Crown College
2018
Massachusetts Institute of Technology
2006-2009
University of Glasgow
2009
Johns Hopkins University
2003
<h2>Summary</h2> SARS-CoV-2 can mutate and evade immunity, with consequences for efficacy of emerging vaccines antibody therapeutics. Here, we demonstrate that the immunodominant spike (S) receptor binding motif (RBM) is a highly variable region S provide epidemiological, clinical, molecular characterization prevalent, sentinel RBM mutation, N439K. We N439K protein has enhanced affinity to hACE2 receptor, viruses have similar <i>in vitro</i> replication fitness cause infections clinical...
Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone public health response to COVID-19. The emergence hypermutated, increasingly transmissible variants concern (VOCs) threaten this strategy. Omicron (B.1.1.529), fifth VOC be described, harbours multiple amino acid mutations in spike, half which lie within receptor-binding domain. Here we demonstrate substantial evasion neutralization by BA.1 and BA.2 vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2...
The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention SARS-CoV-2, meaning there is an urgent need for tools that can be used in unaccustomed working with coronaviruses. Here we report range SARS-CoV-2 research. First, describe facile single plasmid reverse...
An outbreak of acute hepatitis unknown aetiology in children was reported Scotland1 April 2022 and has now been identified 35 countries2. Several recent studies have suggested an association with human adenovirus this outbreak, a virus not commonly associated hepatitis. Here we report detailed case–control investigation find between adeno-associated 2 (AAV2) infection host genetics disease susceptibility. Using next-generation sequencing, PCR reverse transcription, serology situ...
Analysis of metabolomic profiling data from gas chromatography−mass spectrometry (GC/MS) measurements usually relies upon reference libraries metabolite mass spectra to structurally identify and track metabolites. In general, techniques enumerate unidentified metabolites are nonsystematic require manual curation. We present a method software implementation, freely available at http://spectconnect.mit.edu, that can systematically detect components conserved across samples without the need for...
The cyclin-dependent kinases 4 and 6 (Cdk4/6) that drive progression through the G 1 phase of cell cycle play a central role in control proliferation, CDK deregulation is frequent event cancer. Cdk4/6 are regulated by D-type cyclins, which bind to CDKs activate kinase, INK4 family inhibitors. proteins can both monomeric CDK, preventing its association with cyclin, also CDK-cyclin complex, forming an inactive ternary complex. In vivo, binary INK4–Cdk4/6 complexes more abundant than...
Genome sequencing dramatically increased our ability to understand cellular response perturbation. Integrating system-wide measurements such as gene expression with networks of protein-protein interactions and transcription factor binding revealed critical insights into behavior. However, the potential systems biology approaches is limited by difficulties in integrating metabolic across functional levels cell despite their being most closely linked phenotype. To address this limitation, we...
SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that immunodominant spike (S) receptor binding motif (RBM) is most divergent region S, provide epidemiological, clinical, molecular characterization a prevalent RBM variant, N439K. We N439K S protein has enhanced affinity hACE2 receptor, virus similar clinical outcomes in vitro replication fitness as compared wild- type. observed mutation resulted...
Highlights•Unusual genotypes (G1 non 1a/1b or G4 4a/4d) were common in African patients.•11 previously unclassified HCV subtypes represented including novel G1p.•Patients with unusual G1 had a lower SVR rate than any other genotype.•Failures driven by patients treated first generation NS5A inhibitor.•The majority of baseline resistance mutations.Graphical abstractAbstractBackground & AimsHCV which are Europe more prevalent the region, but little is known their response to direct-acting...
We have developed periscope, a tool for the detection and quantification of subgenomic RNA (sgRNA) in SARS-CoV-2 genomic sequence data. The translation genome most open reading frames (ORFs) occurs via intermediates termed "subgenomic RNAs." sgRNAs are produced through discontinuous transcription, which relies on homology between transcription regulatory sequences (TRS-B) upstream ORF start codons that TRS-L, is located 5' UTR. TRS-L immediately preceded by leader sequence. This therefore...
Summary paragraph An outbreak of acute hepatitis unknown aetiology in children was first reported Scotland April 2022. 1 Cases aged <16 years have since been identified 35 countries. 2 Here we report a detailed investigation 9 early cases and 58 control subjects. Using next-generation sequencing real-time PCR, adeno-associated virus (AAV2), detected the plasma 9/9 liver 4/4 patients but 0/13 sera/plasma age-matched healthy controls, 0/12 with adenovirus (HAdV) infection normal function...
ABSTRACT Aspects of intrinsic antiviral immunity are mediated by p ro m yelocytic l eukemia n uclear b ody (PML-NB) constituent proteins. During herpesvirus infection, these proteins independently recruited to nuclear domains that contain infecting viral genomes cooperatively promote genome silencing. Central the execution this particular response is s mall u biquitin-like mo difier (SUMO) signaling pathway. However, participating SUMOylation enzymes not fully characterized. We identify SUMO...
ABSTRACT S mall u biquitin-like mo difier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of host factors that rely on SUMOylation exert their effects, enzymes mediate these events remain be defined. We show unconjugated SUMO levels are largely maintained throughout infection regardless presence ICP0, HSV-1 SUMO-targeted ubiquitin ligase. Moreover, in absence high-molecular-weight...
Tick-borne encephalitis virus (TBEV) is a member of the genus Flavivirus. It can cause serious infections in humans that may result encephalitis/meningoencephalitis. Although several studies have described involvement specific genes host response to TBEV infection central nervous system (CNS), overall network remains poorly characterized. Therefore, we investigated DAOY cells (human medulloblastoma derived from cerebellar neurons) (Neudoerfl strain, Western subtype) characterize...
Using deep sequencing technologies such as Illumina's platform, it is possible to obtain reads from the viral RNA population revealing genome diversity within a single host. A range of software tools and pipelines can transform raw into Sequence Alignment Mapping (SAM) files. We propose that interpretation should process these SAM files, directly translating individual amino acids in order extract statistics interest proportion different acid residues at specific sites. This preserves...
Abstract SARS-CoV-2, the causative agent of COVID-19, emerged in Wuhan, China December 2019 and spread rapidly throughout world. Understanding introductions this new coronavirus different settings may assist control efforts establishment frameworks to support rapid response future infectious disease outbreaks. We investigated first four weeks emergence SARS-CoV-2 virus Scotland after case reported on 1st March 2020. obtained full genome sequences from 452 individuals with a...
Wolbachia are widespread maternally-transmitted bacteria of arthropods that often spread by manipulating their host's reproduction through cytoplasmic incompatibility (CI). Their invasive potential is currently being harnessed in field trials aiming to control mosquito-borne diseases. genomes commonly harbour prophage regions encoding the cif genes which confer ability induce CI. Recently, a plasmid-like element was discovered wPip, strain infecting Culex mosquitoes; however, it unclear how...
In normal cells, activation of cyclin-dependent kinases (cdks) requires binding to a cyclin and phosphorylation by the cdk-activating kinase (CAK). The Kaposi's sarcoma-associated herpesvirus encodes protein with similarity D-type cyclins. This KSHV-cyclin activates CDK6, alters its substrate specificity, renders CDK6 insensitive inhibition cdk inhibitor p16 INK4a . Here we investigate regulation CDK6/KSHV-cyclin use purified proteins cell-based assay. We find that can activate independent...
ABSTRACT The viral ubiquitin ligase ICP0 is required for efficient initiation of herpes simplex virus 1 (HSV-1) lytic infection and productive reactivation genomes from latency. has been shown to target a number specific cellular proteins proteasome-dependent degradation during infection, including the promyelocytic leukemia protein (PML) its small ubiquitin-like modified (SUMO) isoforms. We have previously that can catalyze formation unanchored polyubiquitin chains mediate ubiquitination...
Abstract The second SARS virus, SARS-CoV-2, emerged in December 2019, and within a month was globally distributed. It first introduced into Scotland February 2020 associated with returning travellers visitors. By March it circulating communities across the UK, to control COVID-19 cases, prevent overwhelming of National Health Service (NHS), ‘lockdown’ on 23rd restriction people’s movements. To augment public health efforts large-scale genome epidemiology effort (as part Genomics UK (COG-UK)...
Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec , genus family Rhabdoviridae has been associated with human disease but gone undetected since 1970s. We describe detection of LDV in a case undifferentiated fever Uganda by metagenomic sequencing and demonstrate serological response using ELISA pseudotype neutralisation. By screening 997 individuals sampled 2016, we show frequent exposure ledanteviruses 76% seropositive Western Uganda, lower seroprevalence other areas....
Biting midges (Culicoides species) are vectors of arboviruses and were responsible for the emergence spread Schmallenberg virus (SBV) in Europe 2011 likely to be involved other Europe. Improved surveillance better understanding risks require a circulating viral diversity these biting insects. In this study, we expand sequence space RNA viruses by identifying number novel from Culicoides impunctatus (biting midge) using meta-transcriptomic approach. A metaviromic pipeline called MetaViC was...