A5087828697- Viral-associated cancers and disorders
- SARS-CoV-2 and COVID-19 Research
- Lymphoma Diagnosis and Treatment
- Animal Virus Infections Studies
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Parvovirus B19 Infection Studies
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 detection and testing
- Systemic Sclerosis and Related Diseases
- Bacteriophages and microbial interactions
- Chronic Lymphocytic Leukemia Research
- Influenza Virus Research Studies
- HIV Research and Treatment
- Respiratory viral infections research
- Neurogenesis and neuroplasticity mechanisms
- Eosinophilic Disorders and Syndromes
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Immunodeficiency and Autoimmune Disorders
- Plant Disease Resistance and Genetics
- Immunotherapy and Immune Responses
- Polyomavirus and related diseases
Kymab (United Kingdom)
2018-2024
Sanofi (United Kingdom)
2024
Wellcome Sanger Institute
2011-2019
University College London
2013-2014
MRC Laboratory for Molecular Cell Biology
2014
University of Oxford
2013
University of Hong Kong
2013
University of Edinburgh
2013
Hammersmith Hospital
2009
Imperial College London
2009
A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe structure-based design of self-assembling protein nanoparticle immunogens that elicit potent protective antibody responses against in mice. The vaccines display 60 spike receptor-binding domains (RBDs) a highly immunogenic array induce neutralizing titers 10-fold higher than prefusion-stabilized despite 5-fold lower dose. Antibodies elicited by RBD nanoparticles target multiple distinct...
BackgroundSince June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly patient samples provide important information on transmission, evolution, origin.MethodsFull genome deep sequencing was done nucleic acid extracted PCR-confirmed clinical samples. Viral...
Community of antibodies against COVID-19 The severe acute respiratory syndrome coronavirus 2 spike protein is the basis many vaccines and a primary target neutralizing after infection. Coronavirus Immunotherapeutic Consortium (CoVIC), comprising 56 partners across world, has analyzed panel 269 monoclonal (mAbs) and, on competition profiles, sorted 186 mAbs that receptor binding domain into seven communities. Hastie et al . went to structurally analyze representative antibody used pseudovirus...
ABSTRACT The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) 2012 and, to date, has been identified 180 cases with 43% mortality. In this study, we have determined MERS-CoV evolutionary rate, genetic variants virus and their distribution throughout Arabian peninsula, genome positions under positive selection, important features for monitoring adaptation human transmission identifying source infections. Respiratory samples from...
ABSTRACT Epstein-Barr virus (EBV) infects most of the world's population and is causally associated with several human cancers, but little known about how EBV genetic variation might influence infection or EBV-associated disease. There are currently no published wild-type genome sequences from a healthy individual very few genomes diseases. We have sequenced 71 geographically distinct strains cell lines, multiple types primary tumor, blood samples first saliva carrier. show that established...
Whole genome sequencing of viruses directly from clinical samples is integral for understanding the genetics host-virus interactions. Here, we report use sample sparing target enrichment (by hybridisation) viral nucleic acid separation and deep-sequencing herpesvirus genomes a range including saliva, blood, virus vesicles, cerebrospinal fluid, tumour cell lines. We demonstrate effectiveness method by 13 highly cell-associated human generating full length alignments at high read depth....
Saltatory conduction in the nervous system is enabled through intimate association between leading edge of myelin sheath and axonal membrane to demarcate node Ranvier. The 186 kDa neuron specific isoform adhesion molecule neurofascin (Nfasc186) required for clustering voltage gated Na+ channels at node, whilst 155 glial (Nfasc155) assembly correct paranodal junctions. In order understand relationship these vital structures how they are affected multiple sclerosis we have examined expression...
A novel betacoronavirus associated with lethal respiratory and renal complications was recently identified in patients from several countries the Middle East. We report deep genome sequencing of virus directly a patient's sputum sample. Our high-throughput yielded substantial depth sequence assembly showed minority viral variants specimen. Detailed phylogenetic analysis (England/Qatar/2012) revealed its close relationship to European bat coronaviruses circulating among species...
The adaptive immune response selectively expands B- and T-cell clones following antigen recognition by receptors (BCR TCR), respectively. Next-generation sequencing is a powerful tool for dissecting the BCR TCR populations at high resolution, but robust computational analyses are required to interpret such sequencing. Here, we develop novel approach repertoire analysis using established next-generation methods coupled with network construction population analysis. sequences organize into...
ABSTRACT Virus gene sequencing and phylogenetics can be used to study the epidemiological dynamics of rapidly evolving viruses. With complete genome data, it becomes possible identify trace individual transmission chains viruses such as influenza virus during course an epidemic. Here we sequenced 153 pandemic H1N1/09 genomes from United Kingdom isolates first (127 isolates) second (26 waves 2009 their sequences, dates isolation, geographical locations infer genetic epidemiology epidemic in...
Undifferentiated nasopharyngeal carcinoma (NPC) has a 100% association with Epstein-Barr virus (EBV). However, only three EBV genomes isolated from NPC patients have been sequenced to date, and the role of genomic variations in pathogenesis is unclear. We sought obtain sequences multiple biopsy specimens same geographic location order reveal their sequence diversity. Three published (B95-8, C666-1, HKNPC1) were first resequenced using sequencing workflow target enrichment DNA by...
One hundred thirty-eight new Epstein-Barr virus (EBV) genome sequences have been determined. twenty-five of these and 116 from previous reports were combined to produce a multiple-sequence alignment 241 EBV genomes, which we used analyze variation within the viral genome. The type 1/type 2 classification remains major form is defined mostly by EBNA2 EBNA3, but single-nucleotide polymorphisms (SNPs) at EBNA3 locus extend into adjacent gp350 gp42 genes, whose products mediate infection B cells...
Viral gene sequences from an enlarged set of about 200 Epstein-Barr virus (EBV) strains, including many primary isolates, have been used to investigate variation in key viral genetic regions, particularly LMP1, Zp, gp350, EBNA1, and the BART microRNA (miRNA) cluster 2. Determination type 1 2 EBV saliva samples people a wide range geographic ethnic backgrounds demonstrates small percentage healthy white Caucasian British carrying predominantly EBV. Linkage Zp gp350 variants is likely be due...
Here we describe a virus discovery protocol for range of different genera, that can be applied to biopsy-sized tissue samples. Our viral enrichment procedure, validated using canine and human liver samples, significantly improves read copy number increases the length contigs generated by de novo assembly. This in turn enables Illumina next generation sequencing (NGS) platform used as an effective tool from
Due to their shared genetic history, antibodies from the same clonotype often bind epitope. This knowledge is used in immune repertoire mining, where known binders are search bulk sequencing repertoires identify new binders. However, current computational methods cannot epitope convergence between different clonotypes, limiting sequence diversity of antigen-specific that can be identified. We describe how antibody binding site, paratope, cluster with common antigen reactivity clonotypes. Our...
Deep-sequencing methods are rapidly developing in the field of B-cell receptor (BCR) and T-cell (TCR) diversity. These promise to revolutionise our understanding adaptive immune dynamics, identify novel antibodies, allow monitoring minimal residual disease. However, different for BCR TCR enrichment amplification have been proposed. Here we perform first systematic comparison between enrichment, sequencing generating repertoires using large sample numbers. Resampling from same RNA or cDNA...
This study presents 45 new KSHV genomes sequenced from Uganda, a endemic region. We present evidence for the presence of inter- and intragenic recombination across contributing to diversification strains into at least 5 types.
SUMMARY A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe structure-based design of self-assembling protein nanoparticle immunogens that elicit potent protective antibody responses against in mice. The vaccines display 60 copies spike (S) glycoprotein receptor-binding domain (RBD) a highly immunogenic array induce neutralizing titers roughly ten-fold higher than prefusion-stabilized S ectodomain trimer despite more five-fold...
Highly pathogenic avian influenza virus (HPAIV) H5N1 can infect mammals via the intestine; this is unusual since viruses typically respiratory tract. The dissemination of HPAIV following intestinal entry and associated pathogenesis are largely unknown. To assess route spread to other organs determine its pathogenesis, we inoculated infected chicken liver homogenate directly into intestine cats by use enteric-coated capsules. Intestinal inoculation resulted in fatal systemic disease. from...
ABSTRACT Epstein-Barr virus (EBV) is a ubiquitous pathogen of humans that can cause several types lymphoma and carcinoma. Like other herpesviruses, EBV has diversified through both coevolution with its host genetic exchange between strains. Sequence analysis the genome unusually challenging because large number lengths repeat regions within virus. Here we describe sequence assembly internal 1 (IR1; also known as BamW repeats) for more than 70 The diversity latency protein nuclear antigen...
Many regions of the Epstein-Barr virus (EBV) genome, repeated and unique sequences, contribute to geographical variation observed between strains. Here we use a large alignment curated EBV genome sequences identify major sites in type 1 strains; CAO deletion latent membrane protein (LMP1) is most frequent indel present strains from various parts world. Principal component analysis was used patterns sequence nucleotide positions that can distinguish some different regions. Viral also affects...
Abstract Broadly neutralizing antibodies (bnAbs) have promise to protect against HIV infection, but induction of bnAbs by immunization is an unsolved vaccine design challenge. Germline-targeting priming immunogens aim initiate the specifically activating rare bnAb-precursor B cells that can subsequently be matured using suitable heterologous boosting and shepherding immunogens. Several pre-clinical studies, IAVI G001 human clinical trial, demonstrated ability a germline-targeting immunogen,...
Abstract Axonal signals are critical in promoting the survival and maturation of oligodendrocytes during myelination, with contact‐dependent thought to play a key role. However, exact nature these remains unclear. Neural cell adhesion molecule (NCAM) is expressed by both axons ideally localized transduce from axon. This study sought investigate influence NCAM on premyelinating vitro. Both soluble comprising extracellular domain peptide derived fibroblast growth factor receptor (FGFR) binding...
Polyomaviruses infect a diverse range of mammalian and avian hosts, are associated with variety symptoms. However, it is unknown whether the viruses found in all families evolutionary history polyomaviruses still unclear. Here, we report discovery novel polyomavirus European badger (Meles meles), which to our knowledge represents first be characterized family Mustelidae, within carnivoran. Although virus was discovered serendipitously supernatant cell culture inoculated material,...
Human Immunodeficiency Virus 1 (HIV-1) exhibits a wide range of interactions with the host cell but whether viral proteins interact cellular RNA is not clear. A candidate interacting factor trans-activator transcription (Tat) protein. Tat required for expression virus genes activates through an unusual mechanism; binding to stem-loop, transactivation response element (TAR), elongation P-TEFb. HIV-1 has also been shown alter during infection, contributing pathogenesis but, interacts RNAs...