A5073122430- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Metabolism and Genetic Disorders
- Extracellular vesicles in disease
- Cancer therapeutics and mechanisms
- Genetic Neurodegenerative Diseases
- Cell Image Analysis Techniques
- Advanced NMR Techniques and Applications
- Adipose Tissue and Metabolism
- Neurogenetic and Muscular Disorders Research
- ATP Synthase and ATPases Research
- DNA and Nucleic Acid Chemistry
- Single-cell and spatial transcriptomics
- DNA Repair Mechanisms
- RNA modifications and cancer
- Cardiomyopathy and Myosin Studies
- Digital Imaging for Blood Diseases
Newcastle University
2022-2024
Wellcome Centre for Mitochondrial Research
2022-2024
NIHR Newcastle Biomedical Research Centre
2023
University of Newcastle Australia
2023
Newcastle upon Tyne Hospitals NHS Foundation Trust
2023
Abstract In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of inheritance have been described the neuromuscular disease field. Here we show that predicted deleterious SRPK3 , encoding X-linked serine/argenine protein kinase 3, lead a progressive early onset skeletal muscle myopathy only when combination with heterozygous TTN gene. The co-occurrence / was not seen among 76,702 healthy male individuals, and statistical...
Myotonic dystrophy type 1 (DM1) is a dominant autosomal neuromuscular disorder caused by the inheritance of CTG triplet repeat expansion in Dystrophia Myotonica Protein Kinase (DMPK) gene. At present, no cure currently exists for DM1 disease.This study investigates effects 12-week resistance exercise training on mitochondrial oxidative phosphorylation skeletal muscle cohort patients (n = 11, men) comparison to control with normal phosphorylation.Immunofluorescence was used assess protein...
Abstract Genetic processes require the activity of multiple topoisomerases, essential enzymes that remove topological tension and intermolecular linkages in DNA. We have investigated subcellular localisation six human topoisomerases with a view to understanding maintenance mitochondrial Our results indicate mitochondria contain two TOP1MT TOP3A. Using molecular, genomic biochemical methods we find both proteins contribute mtDNA replication, addition decatenation role TOP3A, is stimulated by...
Mitochondrial DNA (mtDNA) deletions which clonally expand in skeletal muscle of patients with mtDNA maintenance disorders, impair mitochondrial oxidative phosphorylation dysfunction. Previously we have shown that these arise and accumulate perinuclear mitochondria causing localised dysfunction before spreading through the fibre. We believe mito-nuclear signalling is a key contributor accumulation spread deletions, knowledge how fibres respond to our understanding disease mechanisms. To...
Abstract Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder, for which no cure exists. This study investigates the effects of 12-week strength training on mitochondrial oxidative phosphorylation in skeletal muscle cohort DM1 patients (n=11, males) comparison to untrained sex-matched healthy subjects. Immunofluorescence was used assess protein levels key respiratory chain subunits complex I (CI) and IV (CIV), markers mass cell membrane individual myofibers sampled from biopsies. We...
Single cell analysis of human skeletal muscle (SM) tissue cross-sections is a fundamental tool for understanding many neuromuscular disorders. For this to be reliable and reproducible, identification individual fibres within microscopy images (segmentation) SM should automatic precise. Biomedical scientists in field currently rely on custom tools general machine learning (ML) models, both followed by labour intensive subjective manual interventions fine-tune segmentation. We believe that...
Abstract Mitochondrial DNA deletions clonally expand in skeletal muscle of patients with mtDNA maintenance disorders, impairing mitochondrial oxidative phosphorylation dysfunction. Previously we have shown that these originally arise and accumulate the perinuclear mitochondria causing localised dysfunction before spreading through fibre. We believe mito-nuclear signalling is a key contributor this process. To further understand role signalling, use imaging mass cytometry to characterise...
Single cell analysis of skeletal muscle (SM) tissue is a fundamental tool for understanding many neuromuscular disorders. For this to be reliable and reproducible, identification individual fibres within microscopy images (segmentation) SM should precise. There currently no or pipeline that makes automatic precise segmentation curation cross-sections possible. Biomedical scientists in field rely on custom tools general machine learning (ML) models, both followed by labour intensive...
Single cell analysis of human skeletal muscle (SM) tissue cross-sections is a fundamental tool for understanding many neuromuscular disorders. For this to be reliable and reproducible, identification individual fibres within microscopy images (segmentation) SM should automatic precise. Biomedical scientists in field currently rely on custom tools general machine learning (ML) models, both followed by labour intensive subjective manual interventions fine-tune segmentation. We believe that...