- Prion Diseases and Protein Misfolding
- Veterinary Equine Medical Research
- Influenza Virus Research Studies
- Exercise and Physiological Responses
- interferon and immune responses
- Heat shock proteins research
- Asthma and respiratory diseases
- Parasitic Infections and Diagnostics
- Autophagy in Disease and Therapy
- Trace Elements in Health
- Photosynthetic Processes and Mechanisms
- Effects of Environmental Stressors on Livestock
- Cholesterol and Lipid Metabolism
- Nicotinic Acetylcholine Receptors Study
- Viral Infections and Vectors
- Cellular transport and secretion
- Estrogen and related hormone effects
- Liver physiology and pathology
- Alzheimer's disease research and treatments
- Reproductive Biology and Fertility
- Hormonal Regulation and Hypertension
- Cardiac Fibrosis and Remodeling
- Phytoestrogen effects and research
- Retinal Development and Disorders
- Burkholderia infections and melioidosis
Roslin Institute
2016-2025
University of Edinburgh
2016-2025
Biotechnology and Biological Sciences Research Council
2016
Newbury College
2010
The Pirbright Institute
2009-2010
Newcastle University
2009
University of Oxford
2009
John Radcliffe Hospital
2009
University of Nottingham
2009
University of Turku
2006
Abstract We report the proteomes of four life‐cycle stages Apicomplexan parasite Eimeria tenella. A total 1868 proteins were identified, with 630, 699, 845 and 1532 found in early oocysts (unsporulated), late (sporulated), sporozoites second‐generation merozoites, respectively. multidimensional protein identification technology shotgun approach identified 812 sporozoites, 1528 merozoites all oocyst proteins, whereas 2‐D gel proteomics 230 98 merozoite proteins. Comparing invasive stages, we...
•Fn14 is upregulated on tumour cells and CAFs, TWEAK expressed by TAMs in human CCA.•TWEAK/Fn14 are progressively during rodent development.•TWEAK/Fn14 signalling induces TAM accumulation via TWEAK-inducible MCP-1 chemotaxis which can be blocked vivo.•TWEAK-inducible factors from pattern macrophages to a TAM-like phenotype.•TWEAK overexpression experimental formation drives CAF proliferation, collagen deposition increases mice. Background & AimsCholangiocarcinoma (CCA) cancer of the hepatic...
Hepatocyte transplantation has shown promise for genetic diseases of the hepatocytes but to date limited efficacy non-genetic forms severe liver injury. Limited cell engraftment and poor function donor in recipient livers impacts clinical utility hepatocyte therapy. The mechanisms underpinning this are poorly understood. We explored a injury model, where predictable levels senescence was induced AhCreMdm2
A comparative proteomic analysis using 2-DE coupled with MALDI-MS and LC-MS/MS was performed in Synechocystis sp. PCC 6803 to identify protein candidates involved acid stress response cyanobacteria. Comparison of soluble proteins from the cytoplasmic fraction cells grown on media set at pH 7.5 5.5 identified four proteins, which showed significant changes abundance. Surprisingly, several general either heat shock family or chaperonins, did not show perceptible fold acidity. Compared...
The global market for protein drugs has the highest compound annual growth rate of any pharmaceutical class but their availability, especially outside US market, is compromised by high cost manufacture and validation compared to traditional chemical drugs. Improvements in transgenic technologies allow valuable proteins be produced genetically-modified animals; several therapeutic from such animal bioreactors are already on after successful clinical trials regulatory approval. Chickens have...
Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by progressive loss of biliary tract architecture) continue to occur after transplantation, negatively affecting function and frequently leading graft retransplantation. To study biological effects organ preservation before we generated murine models that recapitulate procurement static cold storage. In these...
Phosphatidylinositol 4-kinase IIα (PI4KIIα) generates essential phospholipids and is a cargo for endosomal adaptor proteins. Activity-dependent bulk endocytosis (ADBE) the dominant synaptic vesicle mode during high neuronal activity sustained by glycogen synthase kinase 3β (GSK3β) activity. We reveal GSK3β substrate PI4KIIα ADBE via its depletion in primary cultures. Kinase-dead rescues these neurons but not phosphomimetic form mutated at site, Ser-47. Ser-47 peptides inhibit...
To provide an insight into the heterotrophic metabolism of cyanobacteria, a proteomic approach has been employed with model organism Synechocystis sp. PCC 6803. The soluble proteins from grown under photoautotrophic and light-activated conditions were separated by 2-DE identified MALDI-MS or LC-MS/MS analysis. gels made using narrow- micro-range IPG strips allowed quantitative comparison more than 900 spots. Out 67 abundant protein spots identified, 13 increased 9 decreased heterotrophy,...
Autolysosomal dysfunction and unstable microtubules are hallmarks of chronic neurodegenerative diseases associated with misfolded proteins. Investigation impaired protein quality control clearance systems could therefore provide an important avenue for intervention. To investigate this we have used a highly controlled model aggregation, in vitro prion system. Here report that aggregates traffic via autolysosomes the cytoplasm. Treatment natural polyamine spermine clears by enhancing...
Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that induces the rapid onset of T-cell lymphomas in poultry. The MDV-encoded oncoprotein Meq plays an important role oncogenicity, as its deletion abolishes ability to induce tumours. It has been shown previously oncogenicity linked interaction with C-terminal binding protein 1 (CtBP), property also shared by other virus-encoded oncoproteins such adenovirus E1A and Epstein–Barr EBNA3A -3C. Therefore, this study examined...
Ocular coloboma (OC) is a defect in optic fissure closure and common cause of severe congenital visual impairment. Bilateral OC primarily genetically determined shows marked locus heterogeneity. Whole-exome sequencing (WES) was used to analyze 12 trios (child affected with both unaffected parents). This identified de novo mutations 10 different genes eight probands. Three these encoded proteins associated actin cytoskeleton dynamics: ACTG1, TWF1, LCP1. Proband-only WES second unrelated...
Sortase (a transamidase) has been shown to be responsible for the covalent attachment of proteins bacterial cell wall. Anchoring is effected on secreted containing a specific wall motif toward their C-terminus; that sortase A (SrtA) in Gram-positive bacteria often incorporates sequence LPXTG. Such surface are characterized as virulence determinants and play important roles during establishment persistence infection. Intramammary infection with Streptococcus uberis common cause bovine...
Abstract Background Skeletal damage is a challenge for laying hens because the physiological adaptations required egg make them susceptible to osteoporosis. Previously, we showed that genetic factors explain 40% of variation in end lay bone quality and detected quantitative trait locus (QTL) large effect on chicken chromosome 1. The aim this study was combine data from commercial founder White Leghorn population F2 mapping fine-map QTL understand its function terms gene expression...
Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms the prion protein. These aggregated produced misfolding normal protein, PrPC, to disease-associated form, PrPSc, through mechanisms that remain elusive but which require either direct or indirect interaction between PrPC and PrPSc isoforms. A wealth evidence implicates other non-PrP molecules as active participants in process, catalyse conformational conversion provide a...
Abstract Neutrophilic airway inflammation is highly prevalent in racehorses training, with the term mild to moderate equine asthma (MMEA) being applied majority of such cases. Our proposed study largely derived from strong association between MMEA and their entry into a race training program. The objectives this are characterise effect on local pulmonary immune system by defining gene protein expression tracheal wash (TW) samples Thoroughbred prior following commencement training. Multiomics...
Cardiac repair and remodeling following myocardial infarction (MI) is a multifactorial process involving pro-reparative inflammation, angiogenesis fibrosis. Noninvasive imaging using radiotracer targeting these processes could be used to elucidate cardiac wound healing mechanisms. The alpha7 nicotinic acetylcholine receptor (ɑ7nAChR) stimulates macrophage activity angiogenesis, making it potential biomarker in this context. We investigated by assessing vitro cellular expression of ɑ7nAChR,...
The multifunctional NS1 protein of influenza A virus has roles in antagonising cellular innate immune responses and promoting viral gene expression. To better understand the interplay between these functions, we tested effects effector domain mutations known to affect homo-dimerisation or interactions with PI3 kinase Trim25 on ability promote nuclear export mRNAs. dimerisation mutant W187R retained functions binding NXF1 as well stabilising interaction segment 7 mRNAs their export. Two...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still adapting to its new human host. Attention has focussed on the viral spike protein, but substantial variation been seen in ORF8 gene. Here, we show that SARS-CoV-2 protein undergoes signal peptide-mediated processing through endoplasmic reticulum and secreted as a glycosylated, disulphide-linked dimer. The from prototype virus had no major effect viability of variety cell types, or IFN NF-κB signalling. However, it...
Abstract Airway inflammation is highly prevalent in horses, with the majority of non-infectious cases being defined as equine asthma. Currently, cytological analysis airway derived samples principal method assessing lower inflammation. Samples can be obtained by tracheal wash (TW) or lavage respiratory tract (bronchoalveolar (BAL) fluid; BALF). Although BALF cytology carries significant diagnostic advantages over TW for diagnosis asthma, sample acquisition invasive, making it prohibitive...
In Thailand, diabetes mellitus is the most significant risk factor for melioidosis, a severe disease caused by Burkholderia pseudomallei. this study, neutrophils isolated from healthy or diabetic subjects were infected with B. thailandensis E555, variant strain pseudomallei-like capsular polysaccharide used here as surrogate micro-organism At 2 h post-infection, neutrophil proteins subjected to 4-plex iTRAQ-based comparative proteomic analysis. A total of 341 identified in two more samples,...