Professor Jason King
School of Biosciences
Professor
- Profile
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- 2015 - present Royal Society University Research Fellow
- 2013 - present Advanced Vice-Chancellors Fellow, University of Sheffield
- 2007 - 2013 Post-doctoral fellow. CR-UK Beatson Institute. Advisor: Prof. Robert Insall
- 2003 - 2007 PhD. Cardiff University. Advisor: Prof Adrian Harwood.
- 2000 - 2001 MPhil(res) University of Birmingham
- 1996 - 1999 BSc Medical Biochemistry, University of Birmingham
- Research interests
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The main focus of the laboratory is to understand how cells perform macropinocytosis – the bulk capture of extracellular fluid. This plays important and distinct roles in diverse cell types such as macrophages, dendritic cells and neurons, by allowing cells to sample their environment and regulating membrane turnover. However macropinocytosis also allows cancer cells to scavenge the extracellular nutrients required to support their growth, and provides a route for pathogens and prions to enter host cells.
The diverse importance of macropinocytosis has only recently become clear, and both the formation and maturation of macropinosomes is poorly understood. My laboratory is thus trying to answer two fundamental questions:
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How do cells generate the cup-shaped protrusions required to entrap extracellular fluid?
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How are macropinosomes and phagosomes processed after internalisation?
Autophagy and lysosomal degradation pathways
Macroautophagy is a critical process used by cells to recycle nutrients to survive starvation, but also for protein and organelle homeostasis, cellular remodelling, and protection from pathogens and mis-folded proteins. Our primary aim is to understand the underlying mechanisms of autophagic degradation, how specific targets are recruited to autophagosomes, and how this integrates into the larger cellular context.
Our primary experimental system is the soil amoeba Dictyostelium discoideum. This allows us to use powerful molecular techniques to dissect autophagy in a simple model system. In addition, as Dictyostelium exclusively use phagocytosis and macropinocytosis to take up nutrients, they are an excellent model for phagocytic immune cells and allow us to circumvent the experimental limitations of macrophages and neutrophils. We are therefore currently exploiting this system to understand immune cell interactions with a variety of bacterial and fungal pathogens.
Full publication details at: Google Scholar
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- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Phosphatidylinositol 3,5-bisphosphate facilitates axonal vesicle transport and presynapse assembly. Science, 382(6667), 223-230.
- Coordinated ras and rac activity shapes macropinocytic cups and enables phagocytosis of geometrically diverse bacteria. Current Biology, 30. View this article in WRRO
- PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection. PLoS Pathogens, 15(2). View this article in WRRO
- The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the Mycobacterium-containing vacuole but have opposite impact on containing the infection. PLoS Pathogens, 14(12). View this article in WRRO
- Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner. PLoS Pathogens, 13(4). View this article in WRRO
- WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors. Proceedings of the National Academy of Sciences, 113(40), E5906-E5915. View this article in WRRO
- The autophagic machinery ensures nonlytic transmission of mycobacteria. Proceedings of the National Academy of Sciences, 112(7), E687-E692.
- WASH is required for lysosomal recycling and efficient autophagic and phagocytic digestion. Molecular Biology of the Cell, 24(17), 2714-2726. View this article in WRRO
- The induction of autophagy by mechanical stress. AUTOPHAGY, 7(12), 1490-1499.
All publications
Journal articles
- Pharmacological inhibition of ENT1 enhances the impact of specific dietary fats on energy metabolism gene expression. Proceedings of the National Academy of Sciences, 121(36).
- Phosphatidylinositol 3,5-bisphosphate facilitates axonal vesicle transport and presynapse assembly. Science, 382(6667), 223-230.
- A PI(3,5)P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes. Journal of Cell Biology, 222(9).
- Formation and closure of macropinocytic cups in Dictyostelium. Current Biology.
- The Amoebal Model for Macropinocytosis, 41-59.
- A bacterial endosymbiont of the fungus Rhizopus microsporus drives phagocyte evasion and opportunistic virulence. Current Biology.
- Moving the research forward : the best of British biology using the tractable model system Dictyostelium discoideum. Cells, 10(11).
- Dynamic Rac1 inhibition by CYRI helps cells drink, but stops them from driving.. J Cell Biol, 220(9).
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).. Autophagy. View this article in WRRO
- Coordinated ras and rac activity shapes macropinocytic cups and enables phagocytosis of geometrically diverse bacteria. Current Biology, 30. View this article in WRRO
- Water loss regulates cell and vesicle volume. Science, 367(6475), 246-247.
- The endocytic pathways of Dictyostelium discoideum. The International Journal of Developmental Biology, 63(8-9-10), 461-471. View this article in WRRO
- The UK cellular microbiology network: Exploring the host‐bacterial interface. Cellular Microbiology, 21(9).
- Gamma secretase orthologs are required for lysosomal activity and autophagic degradation in Dictyostelium discoideum, independent of PSEN (presenilin) proteolytic function. Autophagy, 15(8), 1407-1418.
- PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection. PLoS Pathogens, 15(2). View this article in WRRO
- The breadth of macropinocytosis research. Philosophical Transactions of the Royal Society B: Biological Sciences, 374(1765), 20180146-20180146.
- The origins and evolution of macropinocytosis. Philosophical Transactions B: Biological Sciences, 374(1765). View this article in WRRO
- Cellular Microbiology Interview - Dr. Jason King.. Cellular Microbiology. View this article in WRRO
- The ESCRT and autophagy machineries cooperate to repair ESX-1-dependent damage at the Mycobacterium-containing vacuole but have opposite impact on containing the infection. PLoS Pathogens, 14(12). View this article in WRRO
- Cryptococcus neoformans escape from Dictyostelium amoeba by both WASH-mediated constitutive exocytosis and vomocytosis. Frontiers in Cellular and Infection Microbiology, 8. View this article in WRRO
- Nutritional Requirements and Their Importance for Virulence of Pathogenic Cryptococcus Species.. Microorganisms, 5(4). View this article in WRRO
- Methods to Monitor and Quantify Autophagy in the Social Amoeba Dictyostelium discoideum. Cells, 6(3). View this article in WRRO
- Drinking problems: Mechanisms of macropinosome formation and maturation.. FEBS Journal. View this article in WRRO
- Mroh1, a lysosomal regulator localized by WASH-generated actin. Journal of Cell Science, 130(10), 1785-1795. View this article in WRRO
- Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner. PLoS Pathogens, 13(4). View this article in WRRO
- Autophagy in Dictyostelium: Mechanisms, regulation and disease in a simple biomedical model.. Autophagy, 13(1), 24-40. View this article in WRRO
- WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors. Proceedings of the National Academy of Sciences, 113(40), E5906-E5915. View this article in WRRO
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy, 12(1), 1-222.
- Erratum. Autophagy, 12(2), 443-443.
- The autophagic machinery ensures nonlytic transmission of mycobacteria. Proceedings of the National Academy of Sciences, 112(7), E687-E692.
- Comparative genome and transcriptome analyses of the social amoeba Acytostelium subglobosum that accomplishes multicellular development without germ-soma differentiation. BMC Genomics, 16. View this article in WRRO
- Vmp1 Regulates PtdIns3P Signaling During Autophagosome Formation inDictyostelium discoideum. Traffic, 15(11), 1235-1246.
- WASH is required for lysosomal recycling and efficient autophagic and phagocytic digestion. Molecular Biology of the Cell, 24(17), 2714-2726. View this article in WRRO
- The use of streptavidin conjugates as immunoblot loading controls and mitochondrial markers for use with Dictyostelium discoideum. BioTechniques, 55(1), 39-41.
- Cyclical Action of the WASH Complex: FAM21 and Capping Protein Drive WASH Recycling, Not Initial Recruitment. Developmental Cell, 24(2), 169-181.
- Mechanical stress meets autophagy: potential implications for physiology and pathology. Trends in Molecular Medicine, 18(10), 583-588.
- SCAR knockouts in Dictyostelium: WASP assumes SCAR's position and upstream regulators in pseudopods.. J Cell Biol, 198(4), 501-508. View this article in WRRO
- Autophagy across the eukaryotes Is S. cerevisiae the odd one out?. AUTOPHAGY, 8(7), 1159-1162.
- Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy, 8(4), 445-544.
- The induction of autophagy by mechanical stress. AUTOPHAGY, 7(12), 1490-1499.
- SCAR/WAVE is activated at mitosis and drives myosin-independent cytokinesis. JOURNAL OF CELL SCIENCE, 123(13), 2246-2255.
- Genetic Control of Lithium Sensitivity and Regulation of Inositol Biosynthetic Genes. PLOS ONE, 5(6). View this article in WRRO
- Chemotaxis: finding the way forward with Dictyostelium. TRENDS IN CELL BIOLOGY, 19(10), 523-530.
- PtdIns(3,4,5)P-3 and inositol depletion as a cellular target of mood stabilizers. BIOCHEMICAL SOCIETY TRANSACTIONS, 37, 1110-1114.
- The mood stabiliser lithium suppresses PIP3 signalling in Dictyostelium and human cells. DISEASE MODELS & MECHANISMS, 2(5-6), 306-312.
- Chemotaxis: TorC before you Akt.... CURRENT BIOLOGY, 18(18), R864-R866.
- Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport-Luebering glycolytic shunt. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105(16), 5998-6003.
- Phospholipase C regulation of phosphatidylinositol 3,4,5-trisphosphate-mediated chemotaxis. MOLECULAR BIOLOGY OF THE CELL, 18(12), 4772-4779.
- Replacement of the essential Dictyostelium Arp2 gene by its Entamoeba homologue using parasexual genetics. BMC GENETICS, 8. View this article in WRRO
- Parasexual genetics of Dictyostelium gene disruptions: identification of a ras pathway using diploids. BMC GENETICS, 4. View this article in WRRO
- Preparation of monodisperse ellipsoidal polystyrene particles. Colloid & Polymer Science, 271(5), 469-479.
- Making cups and rings: the ‘stalled-wave’ model for macropinocytosis. Biochemical Society Transactions.
- Investigating Metabolic and Molecular Ecological Evolution of Opportunistic Pulmonary Fungal Coinfections: Protocol for a Laboratory-Based Cross-Sectional Study. JMIR Research Protocols, 12, e48014-e48014.
- Katnip is required to maintain microtubule function and lysosomal delivery to autophagosomes and phagosomes. Molecular Biology of the Cell.
- The great host‐pathogen war:
UK
cellular microbiology meeting 2020. Cellular Microbiology.
- Co-ordinated Ras and Rac activity shapes macropinocytic cups and enables phagocytosis of geometrically diverse bacteria.
Chapters
- Parasexual genetics using axenic cells. (pp. 125-135).
Preprints
- A role for class I PAKs in the regulation of the excitability of the actin cytoskeleton., Cold Spring Harbor Laboratory.
- Pulses of Class I PI3kinase activity identify the release and recapture of prey from neutrophil phagosomes, Cold Spring Harbor Laboratory.
- The formation and closure of macropinocytic cups in a model system, Cold Spring Harbor Laboratory.
- A PI(3,5)P2 probe reveals PIKfyve is required for Rab7 acquisition and the delivery and fusion of early macropinosomes to phagosomes, Cold Spring Harbor Laboratory.
- Environmental interactions with amoebae as drivers of bacterial-fungal endosymbiosis and pathogenicity, Cold Spring Harbor Laboratory.
- PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction ofLegionellainfection, Cold Spring Harbor Laboratory.
- Katnip is required to maintain microtubule function and lysosomal delivery to autophagosomes and phagosomes, Cold Spring Harbor Laboratory.
- Phosphatidylinositol 3,5-bisphosphate facilitates axonal vesicle transport and presynapse assembly. Science, 382(6667), 223-230.
- Grants
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- BBSRC
- Royal Society
- Teaching activities
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I give lectures at both Level 2 (BMS242) and 3 (BMS376) on autophagy in health and disease, as well as support level 3 and 4, practical and dissertation modules.
- Professional activities and memberships
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- Vice-Chair Gordon Research Seminar on Autophagy in Stress, Development and Disease 2012
- Vice Chancellor’s Advanced Fellow
- Associate editor BMC Cell Biology
- Society for General Microbiology, Eukaryotic Division committee member
- Dictybase Scientific advisory board member
- Opportunities
We advertise PhD opportunities (Funded or Self-Funded) on FindAPhD.com
For further information and details of other projects on offer, please see the department PhD Opportunities page.