A5057641130- Mycobacterium research and diagnosis
- RNA and protein synthesis mechanisms
- Pharmacological Effects of Natural Compounds
- Genomics and Phylogenetic Studies
- Inflammasome and immune disorders
- Tuberculosis Research and Epidemiology
- Diagnosis and treatment of tuberculosis
- RNA modifications and cancer
- Barrier Structure and Function Studies
- Animal Genetics and Reproduction
- Toxoplasma gondii Research Studies
- Chromosomal and Genetic Variations
- Blood donation and transfusion practices
- Helicobacter pylori-related gastroenterology studies
- Neuroscience and Neuropharmacology Research
- Advanced Proteomics Techniques and Applications
- interferon and immune responses
- Aquaculture disease management and microbiota
- Cytomegalovirus and herpesvirus research
- Plant-based Medicinal Research
- Diet and metabolism studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bat Biology and Ecology Studies
- Autoimmune and Inflammatory Disorders
- Atherosclerosis and Cardiovascular Diseases
University of Cambridge
2012-2025
University of Surrey
2023
Ball State University
2023
Wellcome Trust
1999-2017
GlaxoSmithKline (United Kingdom)
2009
Genomics (United Kingdom)
2002
Molecular Sciences Institute
1999
Addenbrooke's Hospital
1999
MRC Human Nutrition Research
1999
BackgroundLimits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across services in maximum donations allowed. We compared standard practice UK with shorter inter-donation intervals used other countries.MethodsIn this parallel group, pragmatic, randomised trial, we recruited donors aged 18 years or older from 25 centres England, UK. By use a computer-based algorithm, men were randomly assigned (1:1:1) 12-week...
Human cytomegalovirus (HCMV) is an important pathogen with multiple immune evasion strategies, including virally facilitated degradation of host antiviral restriction factors. Here, we describe a multiplexed approach to discover proteins innate function on the basis active by proteasome or lysosome during early-phase HCMV infection. Using three orthogonal proteomic/transcriptomic screens quantify protein degradation, high confidence identified 35 enriched in A final screen employed...
The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action diffusible exotoxin, mycolactone. However, its role clinically evident vascular component disease aetiology remains poorly explained. We now dissected mycolactone’s effects on human primary endothelial cells vitro. show that mycolactone-induced changes morphology, adhesion, migration, and permeability are dependent at Sec61...
The phagocyte respiratory burst is crucial for innate immunity. transfer of electrons to oxygen mediated by a membrane-bound heterodimer, comprising gp91phox and p22phox subunits. Deficiency either subunit leads severe immunodeficiency. We describe Eros (essential reactive species), protein encoded the previously undefined mouse gene bc017643, show that it essential host defense via NAPDH oxidase. required expression NADPH oxidase components, p22phox. Consequently, Eros-deficient mice...
We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences been minimally edited searched against protein DNA databases. These data are all displayed on a searchable, publicly available web site at http://fugu.hgmp.mrc.ac.uk/ . With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%–50% each clone. This essentially random set covers nearly 25 Mb (>6%) the genome forms basis series whole analyses which...
ABSTRACT Infection with human cytomegalovirus (HCMV) profoundly affects cellular metabolism. Like in tumor cells, HCMV infection increases glycolysis, and glucose carbon is shifted from the mitochondrial tricarboxylic acid cycle to biosynthesis of fatty acids. However, unlike many where aerobic glycolysis accompanied by suppression oxidative phosphorylation, induces biogenesis respiration. Here, we affinity purified mitochondria used quantitative mass spectrometry determine how proteome...
Uncharacterized and unannotated open-reading frames, which we refer to as novel open reading frames (nORFs), may sometimes encode peptides that remain unexplored for therapeutic opportunities. To our knowledge, no systematic identification characterization of transcripts encoding nORFs or their translation products in cancer, any other physiological process has been performed. We use curated database (nORFs.org), together with RNA-Seq data from The Cancer Genome Atlas (TCGA)...
Haloperidol and olanzapine are widely used antipsychotic drugs in the treatment of schizophrenia other psychotic disorders. Despite extensive research efforts within biopharmaceutical industry academia, exact molecular mechanisms their action remain largely unknown. Since response patients to existing medications can be variable often includes severe side effects, it is critical increase our knowledge on mechanism guide clinical usage new drug development. In this study, we have employed...
Abstract Studies of pituitary‐related disorders would be facilitated by enhanced knowledge the pituitary proteome. To construct a data set human proteins, separate protein extracts were prepared from 15 post‐mortem pituitaries and analyzed independent label‐free nanoflow liquid chromatography mass spectrometry (nLC‐MS E ). The detected mass/time features aligned quantified using Rosetta Elucidator ® system annotated results ProteinLynx Global Server. resulting comprised 1007 unique with...
Mutations in the human NBEAL2 gene cause gray platelet syndrome (GPS), a bleeding diathesis characterized by lack of α granules platelets. The functions protein have not been explored outside biology, but there are reports increased frequency infection and abnormal neutrophil morphology patients with GPS. We therefore investigated role immunity analyzing phenotype Nbeal2-deficient mice. found profound abnormalities immune system, particularly function neutrophils NK cells. Phenotyping showed...
The search for biomarkers to diagnose psychiatric disorders such as schizophrenia has been underway decades. Many molecular profiling studies in this field have focused on identifying individual marker signals that show significant differences expression between patients and the normal population. However, multiple analyte combinations exhibit patterned behaviors less exploited. Here, we present a novel approach of using serum analytes from first onset, drug-naïve controls. strength was...
Unabated activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome is linked with pathogenesis various inflammatory disorders. Polo-like kinase 1 (PLK1) has been widely studied for its role in mitosis. Here, using both pharmacological and genetic approaches, we demonstrate that PLK1 promoted NLRP3 at cell interphase. Using an unbiased proximity-dependent biotin identification (Bio-ID) screen interactome macrophages, show enhanced proximal association upon activation. We...
Abstract Schizophrenia (SCZ) and bipolar disorder are debilitating neuropsychiatric disorders arising from a combination of environmental genetic factors. Novel open reading frames (nORFs) genomic loci that give rise to previously uncharacterized transcripts protein products. In our previous work, we have shown nORFs can be biologically regulated they may play role in cancer rare diseases. More importantly, emerge accelerated regions the genome giving species-specific functions. We...
Abstract In this study, we performed the first high‐throughput and comprehensive proteomic profiling of rat hippocampal proteome. Using a combination 2‐D LC‐MS data analysis with Rosetta Elucidator ® system, identified 1340 unique proteins. Functional classification showed that most these were associated synaptic function comprised high proportion phosphorylated proteins analytically challenging classes membrane such as ion channel receptor subunits.
BackgroundThe INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet shortages. We extended the further 2 years evaluate longer-term risks and benefits of varying intervals, compare routine versus more intensive reminders help donors keep appointments.MethodsThe was parallel group, pragmatic, randomised that recruited aged 18 or older from 25 static donor centres NHS Blood Transplant across England, UK. Here we report...
The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action diffusible exotoxin, mycolactone. However, its role clinically-evident vascular component disease aetiology remains poorly explained. We now dissected mycolactone’s effects on primary endothelial cells vitro and vivo . show that mycolactone-induced changes morphology, adhesion, migration, permeability are dependent at Sec61...
Plasminogen related growth factors (PRGFs) and their receptors play major roles in embryogenesis, tissue regeneration neoplasia. In order to investigate the complexity evolution of PRGF receptor family we have cloned sequenced three for PRGFs teleost fish Fugu rubripes , a model vertebrate with compact genome. One genes isolated encodes orthologue mammalian MET, whilst other two may represent orthologues RON SEA. This is first time been identified single species.
Abstract Novel open reading frames (nORFs) with coding potential may arise from noncoding DNA. Not much is known about their emergence, functional role, fixation in a population or contribution to adaptive radiation. Cichlids fishes exhibit extensive phenotypic diversification and speciation. Encounters new environments alone are not sufficient explain this striking diversity of cichlid radiation because other taxa coexistent the Cichlidae demonstrate lower species richness. Wagner et al....
Abstract Translation products encoded by non canonical or novel open reading frame (ORF) genomic regions are generally considered too small to play any significant biological role, and dismissed as inconsequential. In this study, we show that mutations mapping ORFs have significantly higher pathogenicity scores than in protein-coding regions. Importantly, can translate into protein-like structures with putative independent functions be of relevance disease states, including cancer. We thus...