A5083765071- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Neurobiology and Insect Physiology Research
- Ion channel regulation and function
- Growth Hormone and Insulin-like Growth Factors
- Neuroscience and Neuropharmacology Research
- Genetics, Aging, and Longevity in Model Organisms
- Radiology practices and education
- Innovations in Medical Education
- Diet and metabolism studies
- RNA modifications and cancer
- Clinical Reasoning and Diagnostic Skills
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neural Engineering
- Lipid metabolism and disorders
- Invertebrate Immune Response Mechanisms
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Neurogenetic and Muscular Disorders Research
- T-cell and B-cell Immunology
- Healthcare Quality and Management
- Traumatic Brain Injury Research
- Heat shock proteins research
- Optical Coherence Tomography Applications
- Erythrocyte Function and Pathophysiology
Lancaster University
2023
University of Plymouth
2010-2022
The Francis Crick Institute
1992-2022
Peninsula College of Medicine and Dentistry
2007-2017
University of Cambridge
2001-2014
Addenbrooke's Hospital
2014
University of Exeter
2010-2011
Case Western Reserve University
2004-2011
National Hospital for Neurology and Neurosurgery
2002-2004
University College London
2002-2004
Amphiphysins 1 and 2 are enriched in the mammalian brain proposed to recruit dynamin sites of endocytosis. Shorter amphiphysin splice variants also found ubiquitously, with an enrichment skeletal muscle. At Drosophila larval neuromuscular junction, is localized postsynaptically mutants have no major defects neurotransmission; they viable, but flightless. Like muscles, does not bind clathrin, can tubulate lipids on T-tubules. Amphiphysin a novel phenotype, severely disorganized...
The autosomal recessive neurodegenerative disease spinal muscular atrophy (SMA) results from low levels of survival motor neuron (SMN) protein; however, it is unclear how reduced SMN promotes SMA development. Here, we determined that ubiquitin-dependent pathways regulate neuromuscular pathology in SMA. Using mouse models SMA, observed widespread perturbations ubiquitin homeostasis, including ubiquitin-like modifier activating enzyme 1 (UBA1). physically interacted with UBA1 neurons, and...
Cytoplasmic accumulation and nuclear clearance of TDP-43 characterize familial sporadic forms amyotrophic lateral sclerosis frontotemporal lobar degeneration, suggesting that either loss or gain function, both, cause disease formation. Here we have systematically compared loss- gain-of-function Drosophila TDP-43, TAR DNA Binding Protein Homolog (TBPH), in synaptic function morphology, motor control, age-related neuronal survival. Both TBPH severely affect development result premature...
"Snapshot" images of localized Ca2+ influx into patch-clamped chromaffin cells were captured by using a recently developed pulsed-laser imaging system. Transient opening voltage-sensitive channels gave rise to elevations that had the appearance either "hotspots" or partial rings found immediately beneath plasma membrane. When technique was employed in conjunction with flame-etched carbon-fiber electrodes spatially map release sites catecholamines, it observed entry and catecholamine...
Epidermal growth factor receptor pathway substrate clone 15 (Eps15) is a protein implicated in endocytosis, endosomal sorting, and cytoskeletal organization. Its role is, however, still unclear, because of reasons including limitations dominant-negative experiments apparent redundancy with other endocytic proteins. We generated Drosophila eps15-null mutants show that Eps15 required for proper synaptic bouton development normal levels vesicle (SV) endocytosis. Consistent SV moves from the...
To identify novel proteins required for receptor-mediated endocytosis, we have developed an RNAi-based screening method in Drosophila S2 cells, based on uptake of a scavenger receptor ligand. Some known endocytic are essential endocytosis this assay, including clathrin and alpha-adaptin; however, other important synaptic vesicle not required. In small screen proteins, identified the homologue Vps35, component retromer complex, involved endosome-to-Golgi trafficking. Loss Vps35 inhibits...
Synaptic terminals are known to expand and contract throughout an animal's life. The physiological constraints demands that regulate appropriate synaptic growth connectivity currently poorly understood. In previous work, we identified a Drosophila model of lysosomal storage disease (LSD), spinster ( spin ), with larval neuromuscular synapse overgrowth. Here identify reactive oxygen species (ROS) burden in may be attributable previously lipofuscin deposition dysfunction, cellular hallmark...
Abstract: The effect of inositol 1,4,5‐trisphosphate [Ins‐(1,4,5)P 3 ] and caffeine on Ca 2+ release from digitonin‐per‐meabilised bovine adrenal chromaffin cells was examined by using the indicator fura‐2 to monitor [Ca ]. Permea‐bilised accumulated in presence ATP addition either Ins(1,4,5)P or released 17% 40–50%, respectively, , indicated sustained rises cell suspension. Prior Ins(l,4,5)P had no magnitude response a subsequent caffeine. prevented prior CaCl 2 indicating that blocked...
Abstract The synaptic protein SNAP-25 is an important component of the neurotransmitter release machinery, although its precise function still unknown. Genetic analysis other proteins has yielded valuable information on their role in transmission. In this study, we performed a mutagenesis screen to identify new alleles that fail complement our previously isolated recessive temperature-sensitive allele SNAP-25, SNAP-25ts. 100,000 flies, 26 F1 progeny failed SNAP-25ts and 21 these were found...
We have characterized the effect of Ca(2+)-ATPase inhibitors 2,5-di-(t-butyl)-1,4-benzohydroquinone (tBHQ) and thapsigargin on concentration cytosolic Ca2+ in single bovine adrenal chromaffin cells by video-imaging fura-2-loaded cells. Addition either inhibitor released from internal stores absence external Ca2+. tBHQ was unable to stimulate further release after addition thapsigargin, but could do so tBHQ, indicating that tBHQ-sensitive are a sub-set those sensitive thapsigargin....
Cytokinesis is a highly ordered cellular process driven by interactions between central spindle microtubules and the actomyosin contractile ring linked to dynamic remodelling of plasma membrane. The mechanisms responsible for reorganizing membrane at cell equator its coupling in cytokinesis are poorly understood. We report here that Syndapin, protein containing an F-BAR domain required curvature, contributes around cytokinesis. Syndapin colocalizes with phosphatidylinositol 4,5-bisphosphate...
Retrograde growth factors regulating synaptic plasticity at the neuromuscular junction (NMJ) in Drosophila have long been predicted but their discovery has scarce. In vertebrates, such retrograde produced by muscle include GDNF and neurotrophins (NT: NGF, BDNF, NT3 NT4). NT superfamily members identified throughout invertebrates, so far no functional vivo analysis carried out NMJ invertebrates. The family of proteins is formed DNT1, DNT2 Spätzle (Spz), with sequence, structural conservation...
RNA interference (RNAi) has a range of physiological functions including as defence mechanism against viruses. To protect uninfected cells in multicellular organism, not only cell-autonomous RNAi response is required but also systemic one. However, the route spread remains unclear. Here we show that phagocytosis can be for double-stranded uptake. Double-stranded expressed Escherichia coli induces robust Drosophila S2 cells, with effectiveness comparable to naked dsRNA. We could separate this...
Summary We have previously shown, in a transgenic mouse model, that the pituitary gland is susceptible to CD8 T‐cell‐mediated autoimmunity, triggered by cell‐specific model autoantigen, resulting pan‐anterior hypophysitis and dwarfism. In present study, we now demonstrate antigen dose, T‐cell precursor frequency, degree of lymphopenia context target expression, are important parameters determining time course extent pathological consequences autoimmunity. Furthermore, our data indicate...