A5010467611- Alzheimer's disease research and treatments
- Cell Adhesion Molecules Research
- Prion Diseases and Protein Misfolding
- Protein Structure and Dynamics
- Tissue Engineering and Regenerative Medicine
- Wnt/β-catenin signaling in development and cancer
- Protease and Inhibitor Mechanisms
- Cellular Mechanics and Interactions
- Lysosomal Storage Disorders Research
- Autoimmune and Inflammatory Disorders Research
- Advanced Glycation End Products research
- Angiogenesis and VEGF in Cancer
- Connective Tissue Growth Factor Research
- Marine Ecology and Invasive Species
- Lipid Membrane Structure and Behavior
- Connective tissue disorders research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cancer Cells and Metastasis
- Cellular transport and secretion
- Marine Sponges and Natural Products
- Marine Invertebrate Physiology and Ecology
- 3D Printing in Biomedical Research
- Immune Cell Function and Interaction
- S100 Proteins and Annexins
- Metabolomics and Mass Spectrometry Studies
University of Bristol
2015-2022
Institute of Structural and Molecular Biology
2013-2014
University of Leeds
2009-2014
Fibrils associated with amyloid disease are molecular assemblies of key biological importance, yet how cells respond to the presence remains unclear. Cellular responses may not only depend on chemical composition or properties fibrils, but their physical attributes such as length, width, surface area also play important roles. Here, we report a systematic investigation effect fragmentation structural and fibrils. In addition expected relationship between ability seed, show striking finding...
Protein misfolding and aggregation cause serious degenerative conditions such as Alzheimer’s, Parkinson, prion diseases. Damage to membranes is thought be one of the mechanisms underlying cellular toxicity a range amyloid assemblies. Previous studies have indicated that fibrils can membrane leakage elicit damage, these effects are enhanced by fragmentation fibrils. Here we report direct 3D visualization damage specific interactions lipid bilayer with amyloid-like formed in vitro from β 2...
Amyloid assemblies are associated with several debilitating human disorders. Understanding the intra- and extracellular assembly of normally soluble proteins peptides into amyloid aggregates how they disrupt normal cellular functions is therefore paramount importance. In a recent report, we demonstrated striking relationship between reduced fibril length caused by fragmentation enhanced ability samples to membranes reduce cell viability. These findings have important implications for our...
Abstract Thrombospondins (TSPs) are multidomain glycoproteins with complex matricellular functions in tissue homeostasis and remodeling. We describe a novel role of TSP as Wnt signaling target the basal eumetazoan Hydra . Proteome analysis identified magnipapillata (HmTSP) major component cnidarian mesoglea. In general, domain organization TSPs is related to pentameric bilaterians, phylogenetic analyses formed separate clade high sequence diversity. HmTSP expression polyps was restricted...
The extracellular matrix (ECM) is recognized as a diverse, dynamic, and complex environment that involved in multiple cell-physiological pathological processes. However, the isolation of ECM, from tissues or cell culture, complicated by insoluble cross-linked nature assembled ECM potential contamination extracts with surface intracellular proteins. Here, we describe method for use cultured cells rapid reliably removes to isolate cell-derived downstream experimentation. Through this method,...
Amyloid fibril accumulation is a pathological hallmark of several devastating disorders, including Alzheimer's disease, prion diseases, type II diabetes, and others. Although the molecular factors responsible for amyloid pathologies have not been deciphered, interactions misfolded proteins with cell membranes appear to play important roles in these disorders. Despite increasing evidence involvement amyloid-mediated cytotoxicity, pursuit therapeutic strategies has focused on preventing...
Natural killer (NK) cell secretory lysosome exocytosis and cytotoxicity are impaired in familial hemophagocytic lymphohistiocytosis type 4 (FHL-4), a disorder caused by mutations the gene encoding SNARE protein syntaxin 11. We show that 11 binds to SNAP23 NK cells this interaction is reduced FHL-4 truncation frameshift mutation proteins delete all or part of domain In contrast mutant bound Sec-1/Munc18-like (SM) Munc18-2. demonstrate C-terminal cysteine rich region 11, which deleted mutants,...
Thrombospondins (TSPs) are evolutionarily-conserved, secreted glycoproteins that interact with cell surfaces and extracellular matrix (ECM) have complex roles in interactions. Unlike the structural components of ECM form networks or fibrils, TSPs deposited into as arrays nanoscale puncta. The cellular molecular mechanisms for patterning poorly understood. In present study, we investigated whether TSP cell-derived involves actin cytoskeletal pathways oligomer state. From tests a suite...
The extracellular matrix (ECM) is recognized as a diverse, dynamic, and complex environment that involved in multiple cell-physiological pathological processes. However, the isolation of ECM, from tissues or cell culture, complicated by insoluble cross-linked nature assembled ECM potential contamination extracts with surface intracellular proteins. Here, we describe method for use cultured cells rapid reliably removes to isolate cell-derived downstream experimentation. Through this method,...
The matricellular glycoprotein thrombospondin-1 (TSP1) has complex roles in the extracellular matrix (ECM) and at cell surfaces, but relatively little is known about its intracellular associations prior to secretion. To search for novel interactions of TSP1 situ, we carried out a biotin ligase-based interactome screen identified protein disulfide isomerase A3 (PDIA3/ERp57) as candidate binding protein. In validation, PDIA3 were established bind vitro colocalize endoplasmic reticulum human...