A5102904076- Plant Pathogenic Bacteria Studies
- Plant-Microbe Interactions and Immunity
- Legume Nitrogen Fixing Symbiosis
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Inflammasome and immune disorders
- Neurological Disease Mechanisms and Treatments
- Plant Pathogens and Fungal Diseases
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Immune Response and Inflammation
- Plant pathogens and resistance mechanisms
- Genomics and Phylogenetic Studies
- Polysaccharides and Plant Cell Walls
- Trace Elements in Health
- Plant Pathogens and Resistance
- Barrier Structure and Function Studies
- Immune cells in cancer
- Crystallization and Solubility Studies
- Amyotrophic Lateral Sclerosis Research
- Polysaccharides Composition and Applications
- Tryptophan and brain disorders
- X-ray Diffraction in Crystallography
- Microbial infections and disease research
- Ion Channels and Receptors
UK Dementia Research Institute
2019-2024
University of Edinburgh
2019-2024
Manchester Academic Health Science Centre
2017-2021
University of Manchester
2016-2021
Edinburgh College
2019
University of Chicago
2011
Sainsbury Laboratory
1993-2006
John Innes Centre
1991-2006
Norwich Research Park
1993-2006
University of Newcastle Australia
1998
Mutations in the seven clustered rpf genes cause downregulated synthesis of extracellular enzymes and reduced virulence Xanthomonas campestris pathovar ( Xcc ). The phenotype mutants one genes, rpfF , can be restored by a diffusible factor (DSF) produced all strains tested, apart from rpfB mutants. DSF accumulates early stationary phase (when is maximal), but levels decline subsequently. Addition to exponentially‐growing wild‐type bacteria does not precocious enzyme synthesis. are expressed...
Saponins are glycosylated plant secondary metabolites found in many major food crops [Price, K. R., Johnson, I. T. & Fenwick, G. R. (1987) CRC Crit. Rev. Food Sci. Nutr. 26, 27-133]. Because saponins have potent antifungal properties and present healthy plants high concentrations, these molecules may act as preformed chemical barriers to fungal attack. The isolation of mutants defective saponin biosynthesis represents a powerful strategy for evaluating the importance compounds defense. oat...
Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1) and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible for the processing of proinflammatory cytokine interleukin-1β implicated in many inflammatory diseases. Here we show that several clinically approved widely used NSAIDs fenamate class are effective selective inhibitors via inhibition volume-regulated anion channel macrophages, independently COX Flufenamic acid mefenamic...
Interleukin-1β (IL-1β) is a critical regulator of the inflammatory response. IL-1β not secreted through conventional ER–Golgi route protein secretion, and to date its mechanism release has been unknown. Crucially, secretion depends upon processing precursor form following activation multimolecular inflammasome complex. Using novel reversible pharmacological inhibitor process, in combination with biochemical, biophysical, real-time single-cell confocal microscopy macrophage cells expressing...
Synapse loss correlates with cognitive decline in Alzheimer's disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence any glial involvement removal AD remains to be established. Here we observe astrocytes and brains contain greater amounts of synaptic protein compared non-disease controls, that proximity amyloid-β plaques the APOE4 risk gene exacerbate this effect. In culture, primary phagocytose patient-derived synapses more...
In Arabidopsis ecotype Landsberg erecta (Ler), RPP5 confers resistance to the pathogen Peronospora parasitica. is part of a clustered multigene family encoding nucleotide binding-leucine-rich repeat (LRR) proteins. We compared 95 kb DNA sequence carrying Ler haplotype with corresponding 90 Columbia (Col-0). Relative remainder genome, and Col-0 haplotypes exhibit remarkable intraspecific polymorphism. The gene probably evolved by extensive recombination between LRRs from an RPP5-like...
Antifungal saponins occur in many plant species and may provide a preformed chemical barrier to attack by phytopathogenic fungi. Some fungal pathogens can enzymatically detoxify host saponins, which suggests that saponin detoxification determine the range of these A gene encoding detoxifying enzyme was cloned from cereal-infecting fungus Gaeumannomyces graminis. Fungal mutants generated targeted disruption were no longer able infect saponin-containing oats but retained full pathogenicity...
Alzheimer's disease is a devastating neurodegenerative with dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing disease. Zinc deficiency most prevalent malnutrition in world may be factor for potentially through enhanced inflammation, although evidence this limited. Here we provide epidemiological suggesting that zinc supplementation was associated reduced slower cognitive decline, people mild impairment. Using...
NLRP3 is a receptor important for host responses to infection, yet also known contribute devastating diseases such as Alzheimer's disease, diabetes, atherosclerosis, and others, making inhibitors sought after. One of the currently in use 2-aminoethoxy diphenylborinate (2APB). Unfortunately, addition inhibiting NLRP3, 2APB displays non-selective effects on cellular Ca2+ homeostasis. Here, we chemical scaffold build series inhibitors, NBC series, which inhibit inflammasome vitro vivo without...
Interleukin (IL)-1 family cytokines potently regulate inflammation, with the majority of IL-1 proteins being secreted from immune cells via unconventional pathways. In many cases, secretion appears to be closely coupled cell death, yet secretory mechanisms involved remain poorly understood. Here, we studied three best-characterized members superfamily, IL-1α, IL-1β, and IL-18, in a range conditions types, including murine bone marrow–derived peritoneal macrophages, human monocyte–derived...
The interleukin-1 (IL-1) receptor and ligand families are components of the immune system. Knowledge their evolutionary history is essential to understand function. Using chromosomal anatomy sequence similarity, we show that IL-1 family members related nine likely formed from duplication modification a proto-IL-1R1 receptor. ligands have different history. first proto-IL-1β gene coincided with events resulted in majority members. However, large distances observed for IL-1α, IL-18 IL-33...
Inoculation of pepper leaves, Capsicum annuum cv. Early Calwonder ECW 10R, with strains Xanthomonas campestris led to an accumulation the phenolic conjugates feruloyltyramine (FT) and p-coumaroyltyramine (CT) 24 h postinoculation in nonhost- gene-for-gene-determined incompatible interactions X. pv. vesicatoria, respectively. In contrast, neither compound was detected compatible vesicatoria. The FT CT preceded by increase extractable activity tyrosine decarboxylase as well increases...
A DNA fragment from Xanthomonas campestris pv. that partially restored the carbohydrate fermentation pattern of a cya crp Escherichia coli strain was cloned and expressed in E. coli. The nucleotide sequence this revealed presence 700-base-pair open reading frame coded for protein highly similar to catabolite activation factor (CAP) (accordingly named CLP CAP-like protein). An X. clp mutant constructed by reverse genetics. This not affected utilization various carbon sources but had strongly...
Clinical correlations between bacterial infections and rejection suggest a hypothesis that innate immune stimulation by results in the production of inflammatory cytokine facilitate bystander T-cell activation, increased alloreactivity inhibition tolerance induction. Previous studies demonstrated IFNβ produced during an infection with model bacterium, Listeria monocytogenes, prevented induction transplantation mice anti-CD154 donor-specific transfusion (DST) (1). We investigated impact two...
Xanthomonas campestris pv ( Xcc ) is a plant pathogenic bacterium that controls the production of pathogenicity factors in part by cluster genes designated rpf (regulation factors). Sequence analysis one these rpfA revealed an open reading frame with amino acid sequence similarity to aconitases from other bacteria. Aconitase activity was lower cellular extracts ::Tn 5 mutant than those wild type. A zymogram aconitase after native gel electrophoresis showed presence two distinct ; major...
The gum gene cluster of Xanthomonas campestris pv. comprises 12 genes whose products are involved in the biosynthesis extracellular polysaccharide xanthan. These expressed primarily as an operon from a promoter upstream first gene, gumB. Although regulation xanthan synthesis vitro has been well studied, nothing is known its planta. A reporter plasmid was constructed which region fused to gusA. In liquid cultures, expression gumgusA correlated closely with production xanthan, although low...
Infection and injury of the gut are associated with cell damage release molecules such as extracellular adenosine 5′‐triphosphate (ATP), which is recognised by purinergic P2X7 receptor (P2X7R). P2X7R widely expressed in antigen‐presenting cells (APCs) epithelial cells, but role on poorly understood. We investigated intestinal epithelium vitro vivo using two model infections, Toxoplasma gondii Trichinella spiralis . Lipopolysaccharide ATP treatment infection T. did not promote...
Microglial endolysosomal (dys)function is strongly implicated in neurodegenerative disease. Transcriptomic studies show that a microglial state characterised by set of genes involved function induced both mouse Alzheimer’s disease (AD) models and human AD brain, the emergence this emphasised females. Cst7 (encoding cystatin F) among most highly upregulated these microglia. However, despite such striking robust upregulation, not understood. Here, we crossed -/- mice with App NL-G-F to test...
In mammalian metallothionein Zn<sup>2+</sup> is exclusively coordinated to Cys-thiolate form clusters in which the metal thermodynamically stable but also kinetically labile. By contrast, little known about coordination prokaryotic metallothionein, SmtA. 3 nmol of Zn<sup>2+</sup>nmol<sup>−1</sup> SmtA were displaced by 8 <i>p-</i>(hydroxymercuri)phenylsulfonate implicating eight nine Cys three ions. None associated with was accessible 4-(2-pyridylazo)resorcinol prior addition...
Pre-treatment of leaves pepper (Capsicum annuum) with lipopolysaccharide (LPS) preparations from enteric bacteria and Xanthomonas campestris could prevent the hypersensitive response caused by an avirulent X. strain. By use a range deep-rough mutants, minimal structure in Salmonella LPS responsible for elicitation this effect was determined to be lipid A attached disaccharide 2-keto-3-deoxyoctulosonate; alone free core oligosaccharide Ra mutant were not effective. For Xanthomonas, had...