A5036721635- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Trace Elements in Health
- Animal Virus Infections Studies
- Clostridium difficile and Clostridium perfringens research
- Mosquito-borne diseases and control
- Alzheimer's disease research and treatments
- Human-Animal Interaction Studies
- Antibiotic Resistance in Bacteria
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Bacterial Identification and Susceptibility Testing
- Animal Genetics and Reproduction
- Amino Acid Enzymes and Metabolism
- Lysosomal Storage Disorders Research
- Streptococcal Infections and Treatments
- RNA regulation and disease
- Nuclear Structure and Function
- Ovarian cancer diagnosis and treatment
- Viral Infections and Vectors
- Primate Behavior and Ecology
- Neuroinflammation and Neurodegeneration Mechanisms
- Vector-borne infectious diseases
University of Edinburgh
2017-2025
Roslin Institute
2017-2025
Scottish National Blood Transfusion Service
2022
Edinburgh College
2021
Virologie et Immunologie Moléculaires
2008-2013
The abnormally folded form of the prion protein (PrP(Sc)) accumulating in nervous and lymphoid tissues prion-infected individuals can be naturally cleaved to generate a N-terminal-truncated fragment called C2. Information about identity cellular proteases involved this process its possible role biology has remained limited controversial. We investigated PrP(Sc) N-terminal trimming different cell lines primary cultured nerve cells, brain spleen tissue from transgenic mice infected by ovine...
Abstract Feline cognitive dysfunction syndrome (CDS) is an age-related neurodegenerative disorder, comparable to dementia in people, characterised by behavioural changes such as increased vocalisation, altered social interactions, sleep-wake cycle, disorientation and house-soiling. Although the underlying mechanisms remain poorly understood, pathologies similar those observed Alzheimer’s disease (AD), have been identified brains of aged or CDS-affected cats, including brain atrophy, neuronal...
Abstract After peripheral infections, the initial accumulation of prions within secondary lymphoid tissues is essential for transmission disease to brain. Macrophages are considered sequester or destroy prions, but little was known their impact on susceptibility after a infection. Inflammation in peritoneal cavity can trigger macrophage disappearance reaction, whereby macrophages temporarily contained cellular aggregates mesothelium. We studied bacterial lipopolysaccharide (LPS)-mediated...
Variant Creutzfeldt–Jakob disease (vCJD) is a fatal zoonotic caused by the ingestion of bovine spongiform encephalopathy (BSE)-infected meat products. Although number vCJD cases due to dietary exposure has significantly declined, true burden subclinical infections remains uncertain. Several large-scale surveys using appendix tissue samples have indicated presence abnormal prion protein (PrP Sc ; for scrapie) in lymphoid small proportion UK population. These may represent silent carriers...
Clostridium perfringens poses a serious threat to small ruminants by causing moderate severe enterotoxaemia. Due its ability produce wide arsenal of toxins, it is ranked among the most prevalent and important pathogens in livestock. This study focused on molecular characterization different types along with their antimicrobial resistance profile. An overall higher prevalence C. (46.1%) was detected based mPCR sheep goats (healthy diseased) Punjab province, Pakistan. The majority isolates...
ABSTRACT Infection by prions involves conversion of a host-encoded cell surface protein (PrP C ) to disease-related isoform Sc ). PrP carries two glycosylation sites variably occupied complex N-glycans, which have been suggested previous studies influence the susceptibility these diseases and determine characteristics prion strains. We used Rov system, is susceptible sheep prions, generate series mutants with mutations at one or both attachment sites. examined their subcellular trafficking...
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...
Variant Creutzfeldt-Jakob disease (vCJD) is a human prion resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases vCJD by blood transfusion necessitate on-going risk reduction measures to protect supplies, such as leucodepletion (removal white cells, WBCs). This study set out determine the risks labile components (red platelets, plasma) commonly used in medicine, and effectiveness preventing infection, using BSE-infected sheep model. All were capable...
Efforts to prevent human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) by contaminated blood would be aided the development a sensitive diagnostic test that could routinely used screen donations. As samples from vCJD patients are extremely rare, here we describe optimisation real-time quaking-induced conversion (RT-QuIC) for detection PrPSc (misfolded prion protein, marker infection) in an established large animal model vCJD, sheep experimentally infected with bovine...
Dysfunction of the endoplasmic reticulum associated protein degradation/proteasome system is believed to contribute initiation or aggravation neurodegenerative disorders with misfolding, and there some evidence suggest that proteasome dysfunctions might be implicated in prion disease. This study investigated effect inhibitors on biogenesis both cellular (PrP(C)) abnormal (PrP(Sc)) forms CAD neuronal cells, a newly introduced cell system. In uninfected impairment altered intracellular...
Abstract Infectious prion diseases have very long incubation periods, and the role that subclinical infections play in transmission, persistence re-emergence of these is unclear. In this study, we used a well-established model vCJD (sheep experimentally infected with bovine spongiform encephalopathy, BSE) to determine prevalence infection following exposure by blood transfusion from donors. Many recipient sheep survived for years post-transfusion no clinical signs disease-associated PrP (PrP...
Abstract Infectious prion diseases have very long incubation periods, and the role that subclinical infections play in transmission, persistence re-emergence of these is unclear. In this study, we used a well-established model vCJD (sheep experimentally infected with bovine spongiform encephalopathy, BSE) to determine prevalence infection following exposure by blood transfusion from donors. Many recipient sheep survived for years post-transfusion no clinical signs disease-associated PrP (PrP...