A5028534093- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Food Allergy and Anaphylaxis Research
- Immune Response and Inflammation
- Animal Disease Management and Epidemiology
- Allergic Rhinitis and Sensitization
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Dermatology and Skin Diseases
- Antimicrobial Peptides and Activities
- Genomics and Phylogenetic Studies
- RNA regulation and disease
- Microbial infections and disease research
- Parasitic infections in humans and animals
- Parasite Biology and Host Interactions
- Asthma and respiratory diseases
- Renal and related cancers
- Animal Virus Infections Studies
- Virus-based gene therapy research
- Eosinophilic Esophagitis
- Parasites and Host Interactions
- Eating Disorders and Behaviors
- Influenza Virus Research Studies
- Renal cell carcinoma treatment
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
Wellcome Sanger Institute
2021-2024
Population Health Research Institute
2021
St George's, University of London
2021
University of London
2016-2021
Royal Veterinary College
2009-2018
BackgroundThe influence of early exposure to allergenic foods on the subsequent development food allergy remains uncertain.ObjectiveWe sought determine feasibility introduction multiple exclusively breast-fed infants from 3 months age and effect breastfeeding performance.MethodsWe performed a randomized controlled trial. The group (EIG) continued with sequential 6 foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), wheat; standard followed UK infant feeding...
BackgroundEarly introduction of dietary peanut in high-risk infants with severe eczema, egg allergy, or both prevented allergy at 5 years age the Learning Early About Peanut Allergy (LEAP) study. The protective effect persisted after 12 months avoiding peanuts 12-month extension LEAP study (LEAP-On). It is unclear whether this benefit allergen and allergic disease specific.ObjectiveWe sought to assess early on development disease, food sensitization, aeroallergen sensitization.MethodsAsthma,...
Abstract Genetic redundancy has evolved as a way for human cells to survive the loss of genes that are single copy and essential in other organisms, but also allows tumours despite having highly rearranged genomes. In this study we CRISPR screen 1191 gene pairs, including paralogues known predicted synthetic lethal interactions identify 105 combinations whose co-disruption results cellular fitness. 27 pairs influence fitness across multiple cell lines FAM50A/FAM50B , two unknown function....
The Enquiring About Tolerance (EAT) study was a randomized trial of the early introduction allergenic solids into infant diet from 3 months age. intervention effect did not reach statistical significance in intention-to-treat analysis primary outcome.We sought to determine whether infants at high risk developing food allergy benefited introduction.A secondary performed groups: nonwhite infants; with visible eczema enrollment, severity determined by SCORAD; and enrollment sensitization...
Food allergy is thought to develop through transcutaneous sensitization, especially in the presence of skin barrier impairment and inflammation. Regular moisturizer application infant could potentially promote sensitization development food allergy.We tested this hypothesis Enquiring About Tolerance (EAT) study population.The EAT was a population-based randomized clinical trial conducted from January 15, 2008, August 31, 2015, recruited 1303 exclusively breastfed 3-month-old infants their...
Toll-like receptor (TLR)-mediated vascular inflammation, inducible by - amongst other factors auto-antibodies, is increasingly recognized as a potential mediator of cardiovascular disease. We investigated whether anti-apolipoprotein (Apo)A-1 IgG was associated with pro-inflammatory cytokine profile in myocardial infarction (MI) patients and anti-ApoA-1 elicited response activating TLRs.As surrogate markers atherosclerotic plaque vulnerability, interleukin (IL)-6, tumour necrosis factor...
Abstract Many variants that we inherit from our parents or acquire de novo somatically are rare, limiting the precision with which can associate them disease. We performed exhaustive saturation genome editing (SGE) of BAP1 , disruption is linked to tumorigenesis and altered neurodevelopment. experimentally characterized 18,108 unique variants, 6,196 were found have abnormal functions, then used these data evaluate phenotypic associations in UK Biobank. also a large population-ascertained...
ABSTRACT TLRs mediate recognition of a wide range microbial products, including LPS, lipoproteins, flagellin, and bacterial DNA, signaling through leads to the production inflammatory mediators. In addition TLRs, many other surface receptors have been proposed participate in innate immunity recognition, some these, for example, C-type lectins, is likely cooperate with TLR defining responses. present study, we examined importance ECD intracellular TIR domain boTLR2 huTLR2 induce...
BackgroundThe Enquiring About Tolerance (EAT) study examined whether the early introduction of 6 allergenic foods from 3 months age in exclusively breastfed infants prevented development food allergy. The intervention was effective per-protocol analysis for allergy to 1 or more and egg peanut individually, but only 42% group (EIG) children met criteria.ObjectiveWe sought identify which factors were responsible nonadherence EAT study.MethodsFactors influencing adherence within key period EIG...
Leucine-rich repeats (LRRs) are versatile motifs present in more than 6000 proteins throughout the phylogenetic kingdom. Tandem LRRs generate a characteristic horseshoe with diverse range of functions. Fulfilling key role innate immune system, form TLR and NOD-like receptor (NLR) pathogen-recognition domain. Host–pathogen interactions mediated by drive those involved ligand recognition to become distinct from their consensus motif. Most between 21 30 residues; however, large insertions...
BackgroundThe early introduction group participants of the Enquiring About Tolerance study were asked to undertake a proscriptive regimen and sustained consumption 6 allergenic foods. It was envisaged that this might be challenging, families presented with an open-text question express any problems they experiencing in recurring online questionnaires.ObjectiveWe sought analyze these questionnaire responses aim identifying challenges associated regular foods.MethodsThree combinations interim...
Pathogenic variants in RAD51C confer an elevated risk of breast and ovarian cancer, while individuals homozygous for specific alleles may develop Fanconi anemia. Using saturation genome editing (SGE), we functionally assess 9,188 unique variants, including >99.5% all possible coding sequence single-nucleotide alterations. By computing changes variant abundance Gaussian mixture modeling (GMM), classify 3,094 to be disruptive use clinical truth sets reveal accuracy/concordance classification...
Abstract Melanoma represents ~5% of all cutaneous malignancies, yet accounts for the majority skin cancer deaths due to its propensity metastasise. To develop new therapies, novel target molecules must be identified and accessibility cell surface proteins makes them attractive targets. Using CRISPR activation technology, we screened a library guide RNAs targeting membrane protein-encoding genes identify whose upregulation enhances metastatic pulmonary colonisation capabilities tumour cells...
Schistosomiasis, the most important helminthic disease of humanity, is caused by infection with parasitic flatworms genus Schistosoma . The driven parasite eggs becoming trapped in host tissues, followed inflammation and granuloma formation. Despite abundant transcriptome data for developmental stages three main human-infective schistosome species— mansoni , S. japonicum haematobium —the transcriptomic profiles developing remain under unexplored. In this study, we performed RNAseq laid vitro...
Fumarate hydratase (FH) is a mitochondrial enzyme that catalyzes the reversible hydration of fumarate to malate in tricarboxylic acid (TCA) cycle. Germline mutations FH lead hereditary leiomyomatosis and renal cell carcinoma (HLRCC), cancer syndrome characterized by highly aggressive form cancer. Although HLRCC tumors metastasize rapidly, FH-deficient mice develop premalignant cysts kidneys, rather than carcinomas. How Fh1 -deficient cells overcome these tumor-suppressive events during...
In recent years, the focus of disease resistance and susceptibility studies in cattle have been on determining patterns innate immune response key proteins, such as Toll-like receptors (TLR). bovine genome, there are 10 TLR family members and, these, TLR2, TLR4, TLR6 specialized recognition bacterial ligands. Indigenous breeds Anatolia reported to show fewer signs clinical infections, tuberculosis mastitis, it is hypothesized that this might be due a less stringent genetic selection during...
Equine chorionic girdle trophoblast cells play important endocrine and immune functions critical in supporting pregnancy. Very little is known about the genes pathways that regulate development. Our aim was to identify signalling active vivo equine within a 7 days window. We exploited late implantation of conceptus obtain tissue. An Agilent 44K microarray performed using RNA extracted from Chorionic Girdle Chorion (control) pregnancy 27, 30, 31 34 (n=5), corresponding initiation...
Abstract Background Cutaneous leiomyosarcoma (cLMS) is a rare soft tissue neoplasm, showing smooth muscle differentiation, that arises from the mesenchymal cells of dermis. To-date, genetic investigation these tumours has involved studies with small sample sizes and limited analyses identified recurrent somatic mutations in RB1 TP53, copy number gain MYCOD IGF1R, loss PTEN. Objectives To better understand molecular pathogenesis cLMS, we comprehensively explored mutational landscape to...
Compelling evidence suggests that the early interaction between porcine circovirus 2 (PCV-2) and innate immune system is key event in pathogenesis of Post-Weaning Multisystemic Wasting Syndrome (PMWS). Furthermore, PCV2 has been detected bone-marrow samples, potentially enabling an easy spread reservoir for virus. To assess gene-expression differences induced by in-vitro PCV2b infection different three myeloid cell subsets generated from same animal, we used Agilent Porcine Gene Expression...
Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of livestock-associated methicillin-resistant aureus infections in Europe North America. This strain characterised by high promiscuity terms host species also lacks several traditional S. virulence factors. does not however explain apparent ease with which it crosses species-barriers. Recently, TIR-domain containing proteins (Tcps) inhibitng innate immune response were identified some Gram-negative...
ABSTRACT Essential bacterial genes located within operons are particularly challenging to study independently because of coordinated gene expression and the nonviability knockout mutants. Essentiality scores for many operon remain uncertain. Antisense RNA (asRNA) silencing or in-frame disruption may help establish essentiality but can lead polar effects on downstream upstream target gene. Here, Escherichia coli ribF-ileS-lspA-fkpB-ispH was used evaluate possibility studying an essential...