A5052782792- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Hydrology and Watershed Management Studies
- Phagocytosis and Immune Regulation
- Cellular transport and secretion
- Invertebrate Immune Response Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Flood Risk Assessment and Management
- 3D Printing in Biomedical Research
- Advanced biosensing and bioanalysis techniques
- Cell Adhesion Molecules Research
- Extracellular vesicles in disease
- Biocrusts and Microbial Ecology
- Ferroptosis and cancer prognosis
- Water resources management and optimization
- Nanoplatforms for cancer theranostics
- Hippo pathway signaling and YAP/TAZ
- Hydrology and Sediment Transport Processes
- Autophagy in Disease and Therapy
- Physiological and biochemical adaptations
- Immune cells in cancer
- Trace Elements in Health
- Genetics, Aging, and Longevity in Model Organisms
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
University of Glasgow
2019-2025
Cancer Research UK
2025
University of Edinburgh
2019-2024
MRC Centre for Regenerative Medicine
2023-2024
Centre for Inflammation Research
2019-2023
Queen's Medical Centre
2019
Cancer Research UK Scotland Institute
2011-2019
University of Bristol
2016-2019
Glasgow Life
2013
Sydney Water
2011
Apoptosis of cells and their subsequent removal through efferocytosis occurs in nearly all tissues during development, homeostasis, disease. However, it has been difficult to track cell death corpse vivo. We developed a genetically encoded fluorescent reporter, CharON (Caspase pH Activated Reporter, Fluorescence ON), that could emerging apoptotic efferocytic clearance by phagocytes. Using Drosophila expressing CharON, we uncovered multiple qualitative quantitative features coordinated...
Selectively labeling cells with damaged membranes is needed not only for identifying dead in culture, but also imaging membrane barrier dysfunction pathologies vivo. Most permeability stains are permanently colored or fluorescent dyes that need washing to remove their non-uptaken extracellular background and reach good image contrast. Others DNA-binding environment-dependent fluorophores, which lack design modularity, have potential toxicity, can detect permeabilization of cell volumes...
Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, which the edge is driven forward hydrostatic pressure instead of actin. In
Abstract The impact of future climate on runoff generation and the implications these changes for management water resources in a river basin are investigated by running through catchment system models. Two conceptual daily rainfall‐runoff models used to simulate across Macquarie‐Castlereagh region historical (1895–2006) (∼2030) based outputs from 15 23 IPCC AR4 GCMs A1B global warming scenario. estimates as inputs model. mean annual rainfall averaged is 544 mm simulated 34 30 SIMHYD...
Ferroptosis is a distinct form of necrotic cell death caused by overwhelming lipid peroxidation, and emerging evidence indicates major contribution to organ damage in multiple pathologies. However, ferroptosis has not yet been visualized vivo due lack specific probes, which severely limited the study how immune system interacts with ferroptotic cells this process contributes inflammation. Consequently, whether physiological role remained key outstanding question. Here we identify distinct,...
Abstract Cells are thought to adopt mechanistically distinct migration modes depending on cell-type and environmental factors. These assumed be driven by mutually exclusive actin cytoskeletal organizations, which either lamellar (flat, branched network) or cortical (crosslinked the plasma membrane). Here we exploit Drosophila macrophage (hemocyte) developmental dispersal reveal that these cells maintain both a network at their cell front rear. Loss of classical cortex regulators, such as...
Sterile tissue injury is accompanied by an acute inflammatory response whereby innate immune cells rapidly migrate to the site of guided pro-inflammatory chemotactic damage signals released at wound. Understanding this key improving human health, and recent advances in imaging technology have allowed researchers using different model organisms observe vivo. Over decades, offering a unique combination live time-lapse microscopy genetics, fruit fly Drosophila has emerged as powerful system...
The loading controls used for quantitative immunoblotting of mammalian proteins are not appropriate use with Dictyostelium discoideum. Actin levels, example, change greatly during development. In addition, Dictyostelium-specific antibodies other potential control commercially available. Here we demonstrate the labeled streptavidin to detect biotinylated mitochondrial 3-methylcrotonyl-CoA carboxylase α (MCCC1), providing a robust and convenient tool normalization Western blots, as well...
Efficient motility requires polarized cells, with pseudopods at the front and a retracting rear. Polarization is maintained by restricting pseudopod catalyst, active Rac, to front. Here, we show that actin nucleation-promoting factor Wiskott-Aldrich syndrome protein (WASP) contributes maintenance of front-rear polarity controlling localization cellular levels Rac. Dictyostelium cells lacking WASP inappropriately activate Rac rear, which affects their speed. WASP's Cdc42 interacting binding...
Drosophila provides a powerful model in which to study inflammation vivo, and previous studies have revealed many of the key signaling events critical for recruitment immune cells tissue damage. In fly, wounding stimulates rapid production hydrogen peroxide (H
The actin cytoskeleton is the engine that powers inflammatory chemotaxis of immune cells to sites tissue damage or infection. Here we combine genetics with live, in vivo imaging investigate how cytoskeletal rearrangements drive macrophage recruitment wounds Drosophila. We find actin-regulatory protein Ena a master regulator lamellipodial dynamics migrating macrophages where it remodels form linear filaments can then be bundled together by cross-linker Fascin. In contrast, formin Dia...
The SCAR/WAVE complex drives actin-based protrusion, cell migration, and separation during cytokinesis. However, the contribution of individual members to activity whole remains a mystery. This is primarily because depend on one another for stability, which limits scope experimental manipulation. Several studies suggest that Abi, relatively small member, connects signaling localization activation through its polyproline C-terminal tail. We generated deletion series Dictyostelium discoideum...
The SCAR/WAVE complex drives the actin polymerisation that underlies protrusion of front cell and thus migration. However, it is not understood how activity regulated to generate infinite range cellular shape changes observed during motility. What are relative roles subunits complex? signaling molecules do they interact with? And does integrate all this information in order control temporal spatial formation? Unfortunately, interdependence SCAR members has made genetic dissection hard. In...
ABSTRACT Selectively labelling cells with damaged membranes is needed in contexts as simple identifying dead culture, or complex imaging membrane barrier functionality vivo . The commonly used dyes are permanently coloured/fluorescent that simply excluded by intact membranes, but to achieve good image contrast therefore requires removing their extracellular signal washing background subtraction, which not possible Here, we develop fluorogenic probes sensitively and selectively reveal cells,...
Summary Efficient motility requires polarised cells, with anterior pseudopods and a retracting rear. This polarisation that the pseudopod catalyst Rac is restricted to front. Here we show Arp2/3 complex regulator WASP important for maintaining front–rear polarity, using mechanism limits where active localises. Dictyostelium cells lacking inappropriately activate SCAR/WAVE at their rears, leading reduced cell speed. facilitates internalisation of clathrin-coated pits, its Rac-binding CRIB...