A5101632317- Antifungal resistance and susceptibility
- Genomics and Chromatin Dynamics
- Estrogen and related hormone effects
- Fungal Infections and Studies
- RNA Research and Splicing
- Polysaccharides and Plant Cell Walls
- RNA and protein synthesis mechanisms
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Genomics and Phylogenetic Studies
- Immune Cell Function and Interaction
- Aquaculture disease management and microbiota
- Cytokine Signaling Pathways and Interactions
- Chromosomal and Genetic Variations
- Dermatology and Skin Diseases
- Hormonal and reproductive studies
- Genetic diversity and population structure
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Antimicrobial Peptides and Activities
- Glycosylation and Glycoproteins Research
- Inflammation biomarkers and pathways
- Immune cells in cancer
- T-cell and B-cell Immunology
- Nail Diseases and Treatments
- Mechanisms of cancer metastasis
University of Exeter
2021-2024
University of Aberdeen
2009-2022
Medical Research Council
2018-2021
Cancer Research UK
2009-2016
University of Cambridge
2011-2016
University of Wisconsin–Madison
2015
Hutchison/MRC Research Centre
2010-2012
University of Cape Town
2004-2012
Cancer Research UK Cambridge Center
2008-2010
Wellcome Centre for Infectious Diseases Research in Africa
2008
Transcription factors (TFs) direct gene expression by binding to DNA regulatory regions. To explore the evolution of regulation, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) determine experimentally genome-wide occupancy two TFs, CCAAT/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha, in livers five vertebrates. Although each TF displays highly conserved preferences, most is species-specific, aligned events present all species are rare....
CTCF-binding locations represent regulatory sequences that are highly constrained over the course of evolution. To gain insight into how these DNA elements conserved and spread through genome, we defined full spectrum sites, including a 33/34-mer motif, identified five thousand conserved, robust, tissue-independent by comparing ChIP-seq data from six mammals. Our indicate activation retroelements has produced species-specific expansions CTCF binding in rodents, dogs, opossum, which often...
Innate immune cells detect pathogens via pattern recognition receptors (PRRs), which signal for initiation of responses to infection. Studies with Dectin-1, a PRR fungi, have defined novel innate signaling pathway involving Syk kinase and the adaptor CARD9, is critical inducing Th17 fungal We show that another C-type lectin, Dectin-2, also signals contributes dendritic cell (DC) activation by particles. Unlike Dectin-2 couples indirectly, through association FcRgamma chain. In model Candida...
Estrogen receptor-α (ER) is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting have been limited. We purified endogenous ER using an approach termed RIME (rapid immunoprecipitation mass spectrometry of proteins) discovered interactome under agonist- antagonist-liganded conditions cancer cells, revealing transcriptional networks cancer. The estrogen-enriched interactor GREB1, a...
The cohesin protein complex holds sister chromatids in dividing cells together and is essential for chromosome segregation. Recently, has been implicated mediating transcriptional insulation, via its interactions with CTCF. Here, we show different cell types that functionally behaves as a tissue-specific regulator, independent of CTCF binding. By performing matched genome-wide binding assays (ChIP-seq) human breast cancer (MCF-7), discovered thousands genomic sites share estrogen receptor...
C-type lectin receptors (CLRs) that couple with the kinase Syk are major pattern recognition for activation of innate immunity and host defense. CLRs recognize fungi other forms microbial or sterile danger, they induce inflammatory responses through adaptor protein Card9. The mechanisms relaying CLR proximal signals to core Card9 module unknown. Here we demonstrated C-δ (PKCδ) was activated upon Dectin-1-Syk signaling, mediated phosphorylation at Thr231, responsible Card9-Bcl10 complex...
We report 80,388 ESTs from 23 Atlantic salmon ( Salmo salar ) cDNA libraries (61,819 ESTs), 6 rainbow trout Oncorhynchus mykiss (14,544 2 chinook tshawytscha (1317 sockeye nerka (1243 and lake whitefish Coregonus clupeaformis (1465 ESTs). The majority of these are 3′ sequences, allowing discrimination between paralogs arising a recent genome duplication in the salmonid lineage. Sequence assembly reveals 28,710 different S. , 8981 O. 1085 520 1176 C. putative transcripts. annotate submitted...
Abstract Background We have developed and fabricated a salmonid microarray containing cDNAs representing 16,006 genes. The genes spotted on the array been stringently selected from Atlantic salmon rainbow trout expressed sequence tag (EST) databases. EST databases presently contain over 300,000 sequences 175 cDNA libraries derived wide variety of tissues different developmental stages. In order to evaluate utility microarray, number hybridization techniques screening methods tested. Results...
Abstract We recently demonstrated that the β-glucan receptor Dectin-1 (βGR) was major nonopsonic on macrophages (Mφ) for yeast-derived particle zymosan. However, resident peritoneal Mφ, we identified an additional mannan-inhibitable zymosan distinct from Mφ mannose (MR). In this study, have studied mannose-binding potential of murine and dendritic cell-specific ICAM-3-grabbing nonintegrin homolog, SIGN-related 1 (SIGNR1), as a MR Mφ. Both SIGNR1 βGR cooperated in recognition by these When...
The murine molecule dectin-1 (known as the beta-glucan receptor in humans) is an immune cell surface implicated immunological defense against fungal pathogens. Sequence analysis has indicated that extracellular domain a C-type lectin-like domain, and functional studies have established it binds beta-glucans. We report several crystal structures, including high-resolution structure 2.8 angstroms resolution which short soaked natural trapped lattice. In vitro characterization of presence its...
Zymosan is a particulate yeast preparation that elicits high levels of IL-2 and IL-10 from dendritic cells (DC) engages multiple innate receptors, including the Syk-coupled receptor dectin-1 MyD88-coupled TLR2. Here, we show induction by zymosan requires activation ERK MAP kinase in murine DC. Surprisingly, response to completely blocked Syk-deficient DC unaffected MyD88 deficiency. Conversely, TLR2 agonist Pam3Cys dependent Syk The inability ligands couple may explain dependence emphasises...
Despite continuous contact with fungi, immunocompetent individuals rarely develop pro-inflammatory antifungal immune responses. The underlying tolerogenic mechanisms are incompletely understood. Using both mouse models and human patients, we show that infection the pathogenic fungi Aspergillus fumigatus Candida albicans induces a distinct subset of neutrophilic myeloid-derived suppressor cells (MDSCs), which functionally suppress T NK cell Mechanistically, induce MDSCs through pattern...
Piscirickettsia salmonis is the intracellular bacterium that causes salmonid rickettsial septicemia, an infectious disease kills millions of farmed fish each year. The mechanisms used by P. to survive and replicate within host cells are not known. Piscirickettsiosis severe necrosis hematopoietic kidney. Microarray-based experiments with QPCR validation were identify Atlantic salmon macrophage kidney genes differentially transcribed in response infection. Infections confirmed microscopy...
Dectin-1 is the archetypal signaling, non-Toll-like pattern recognition receptor that plays a protective role in immune defense to Candida albicans as major leukocyte for beta-glucans. Dectin-1-deficiency associated with impaired recruitment of inflammatory leukocytes and mediator production at site infection. In this study, we have used mice define mechanisms regulate dectin-1-mediated responses. Myeloid cell activation by dectin-1 controlled inherent cellular programming, distinct...
Human polymorphonuclear leukocytes (PMN) are a first line of defense against fungal infections. PMN express numerous pattern recognition receptors (PRR) that facilitate identification invading microorganisms and ultimately promote resolution disease. Dectin-1 (beta-glucan receptor) is PRR expressed on several cell types has been studied monocytes macrophages. However, the role played by dectin-1 in killing fungi unknown. We investigated ability to mediate human phagocytosis fungicidal...
ChIP-exonuclease (ChIP-exo) is a modified ChIP-seq approach for high resolution mapping of transcription factor DNA sites. We describe an Illumina-based ChIP-exo method which provides global improvement the data quality estrogen receptor (ER) ChIP and insights into motif structure key ER-associated factors. ER pioneer FoxA1 identifies protected with predictable 8 bp overhang from Forkhead motif, we term mesas. show that mesas occur in multiple cellular contexts exist as single or overlapping...
Chromoblastomycosis is a subcutaneous mycosis that remains therapeutic challenge, with no standard treatment and high rates of relapse. On the basis our recent discoveries in mouse models, we tested efficacy topical applications imiquimod to treat patients afflicted this chronic fungal infection. We report results for first 4 recipients imiquimod, all whom displayed marked improvement their lesions, both without concurrent oral antifungal therapy.