Dr Simon Johnston
PhD
Clinical Medicine, School of Medicine and Population Health
Senior Research Fellow
s.a.johnston@sheffield.ac.uk
+44 114 222 2301
+44 114 222 2301
+44 114 222 2702
(lab)
Firth Court
Full contact details
Dr Simon Johnston
Clinical Medicine, School of Medicine and Population Health
Firth Court
Western Bank
Sheffield
S10 2TN
Clinical Medicine, School of Medicine and Population Health
Firth Court
Western Bank
Sheffield
S10 2TN
- Profile
-
For enquiries please contact - ClinMed-Operational@sheffield.ac.uk
- 2018 - Senior Research Fellow. Department of Infection, Immunity and Cardiovascular Disease, Bateson Centre, University of Sheffield.
- 2012 - 2018 Medical Research Council - Career Development Award Fellow, Department of Infection, Immunity and Cardiovascular Disease, MRC Centre for Developmental and Biomedical Genetics. (2012-2014) and Bateson Centre (2014), University of Sheffield.
- 2012 - 2017 Krebs Institute - Fellow, Krebs Institute, University of Sheffield.
- 2011 - 2012 Lister Institute Post-Doctoral Research Associate, University of Birmingham, Birmingham.
- 2010 - 2011 Wellcome Trust - Post-Doctoral Research Associate, University of Birmingham, Birmingham.
- 2007 - 2010 Medical Research Council - Post-Doctoral Research Associate, University of Birmingham, Birmingham.
- 2003 - 2007 PhD Cell Biology, University of Birmingham.
- 2000 - 2003 BSc (Hons) Biochemistry, University of Birmingham.
- Research interests
-
My research group is focused on the study infectious disease to improve patient treatment and to further our fundamental understanding of how the immune system functions. We use a multidisciplinary approach in collaboration with biologists, clinicians, engineers and physicists. In this way we aim to use the best experimental model to answer the specific research question at hand.
We have a particular interest in opportunistic fungal infections in immunocompromise. One example is Cryptococcus neoformans, which is a fungal pathogen of humans and causes hundreds of thousands of deaths in the severely immunocompromised world-wide each year.
Most life-threatening infections are in individuals with AIDS in Africa where it is the most common cause of meningo-encephalitis and the cause of 15% of AIDS-related deaths. In our studies of cryptococcal disease my group has contributed to how the immune system is defective in responding to cryptococcal infection in immunocompromise and what features of cryptococci drive their virulence.
Currently, we have three research priorities:
- Macrophage mediated immunity to opportunistic infection
- Central nervous system pathology in infection and immune system disease
- Mechanisms and regulation of phagocytosis
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection. PLoS Pathogens, 15(3). 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
- A transgenic zebrafish model for the
in vivo
study of the blood and choroid plexus brain barriers using
claudin 5. Biology Open, 7(2), bio030494-bio030494. View this article in WRRO
- The cause and effect of Cryptococcus interactions with the host.. Curr Opin Microbiol, 40, 88-94. View this article in WRRO
- Vomocytosis of live pathogens from macrophages is regulated by the atypical MAP kinase ERK5. Science Advances, 3(8). View this article in WRRO
- Cryptococcus neoformans Intracellular Proliferation and Capsule Size Determines Early Macrophage Control of Infection. Scientific Reports, 6(1), 21489-21489. View this article in WRRO
- Cryptococcus neoformans Thermotolerance to Avian Body Temperature Is Sufficient For Extracellular Growth But Not Intracellular Survival In Macrophages. Scientific Reports, 6. View this article in WRRO
- Immunity to Cryptococcus neoformans and C. gattii during cryptococcosis. Fungal Genetics and Biology, 78, 76-86. View this article in WRRO
- ‘Division of labour’ in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak. Nature Communications, 5, 5194-5194. View this article in WRRO
- Cryptococcus interactions with macrophages: evasion and manipulation of the phagosome by a fungal pathogen.. Cell Microbiol, 15(3), 403-411.
- The human fungal pathogen Cryptococcus neoformans escapes macrophages by a phagosome emptying mechanism that is inhibited by arp2/3 complex- mediated actin polymerisation. PLoS Pathogens, 6(8), 27-28.
All publications
Books
- Cryptococcus From Human Pathogen to Model Yeast. Amer Society for Microbiology.
Journal articles
- Aging-related defects in macrophage function are driven by MYC and USF1 transcriptional programs. Cell Reports, 43(4). View this article in WRRO
- Tribbles 3 deficiency promotes atherosclerotic fibrous cap thickening and macrophage-mediated extracellular matrix remodelling. Frontiers in Cardiovascular Medicine, 9. View this article in WRRO
- Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection. PLoS Pathogens, 18(4).
- Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species. PLoS Pathogens, 17(9). View this article in WRRO
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).. Autophagy. View this article in WRRO
- Neutrophils use selective autophagy receptor Sqstm1/p62 to target Staphylococcus aureus for degradation in vivo in zebrafish. Autophagy. View this article in WRRO
- The autophagic response to Staphylococcus aureus provides an intracellular niche in neutrophils. Autophagy. View this article in WRRO
- PPAR-gamma fun(gi) with prostaglandin. Nuclear Receptor Signaling, 17. View this article in WRRO
- Investigating a novel commensal strain of Candida famata within Daniorerio. Access Microbiology, 1(9).
- Are macrophages the heroes or villains during cryptococcosis?. Fungal Genetics and Biology, 132, 103261-103261.
- Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution. PLOS Biology, 17(5). View this article in WRRO
- 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection. PLoS Pathogens, 15(3). View this article in WRRO
- Inhibition of Classical and Alternative Modes of Respiration in Candida albicans Leads to Cell Wall Remodeling and Increased Macrophage Recognition.. mBio, 10(1). View this article in WRRO
- Bayesian Polytrees with Learned Deep Features for Multi-Class Cell Segmentation. IEEE Transactions on Image Processing, 1-1. View this article in WRRO
- A glucuronoxylomannan epitope exhibits serotype-specific accessibility and redistributes towards the capsule surface during Titanisation of the fungal pathogen Cryptococcus neoformans.. Infection and Immunity. View this article in WRRO
- Strategic Research Funding: A Success Story for Medical Mycology. Trends in Microbiology. 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
- A transgenic zebrafish model for the
in vivo
study of the blood and choroid plexus brain barriers using
claudin 5. Biology Open, 7(2), bio030494-bio030494. View this article in WRRO
- The cause and effect of Cryptococcus interactions with the host.. Curr Opin Microbiol, 40, 88-94. View this article in WRRO
- Nutritional Requirements and Their Importance for Virulence of Pathogenic Cryptococcus Species.. Microorganisms, 5(4). View this article in WRRO
- Vomocytosis of live pathogens from macrophages is regulated by the atypical MAP kinase ERK5. Science Advances, 3(8). View this article in WRRO
- Microevolutionary traits and comparative population genomics of the emerging pathogenic fungus Cryptococcus gattii. Philosophical Transactions of the Royal Society B: Biological Sciences, 371(1709), 20160021-20160021. View this article in WRRO
- Using Flow Cytometry to Analyze Cryptococcus Infection of Macrophages.. Methods Mol Biol, 1519, 349-357. View this article in WRRO
- CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell–like Populations and Diverse Mononuclear Phagocytes. Journal of Immunology, 197(9), 3520-3530. 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
- Cryptococcus neoformans Intracellular Proliferation and Capsule Size Determines Early Macrophage Control of Infection. Scientific Reports, 6(1), 21489-21489. View this article in WRRO
- Cryptococcus neoformans Thermotolerance to Avian Body Temperature Is Sufficient For Extracellular Growth But Not Intracellular Survival In Macrophages. Scientific Reports, 6. View this article in WRRO
- Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages. Cellular Microbiology, 18(1), 80-96. View this article in WRRO
- Immunity to Cryptococcus neoformans and C. gattii during cryptococcosis. Fungal Genetics and Biology, 78, 76-86. View this article in WRRO
- ‘Division of labour’ in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak. Nature Communications, 5, 5194-5194. View this article in WRRO
- Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis. Journal of Clinical Investigation, 124(5), 2000-2008.
- Cryptococcus interactions with macrophages: evasion and manipulation of the phagosome by a fungal pathogen.. Cell Microbiol, 15(3), 403-411.
- Actin polymerization driven by WASH causes V-ATPase retrieval and vesicle neutralization before exocytosis. Journal of Cell Biology, 193(5), 831-839.
- SEC14 is a specific requirement for secretion of phospholipase B1 and pathogenicity of Cryptococcus neoformans. Molecular Microbiology, 80(4), 1088-1101.
- The human fungal pathogen Cryptococcus neoformans escapes macrophages by a phagosome emptying mechanism that is inhibited by arp2/3 complex- mediated actin polymerisation. PLoS Pathogens, 6(8), 27-28.
- Automated analysis of cryptococcal macrophage parasitism using GFP-tagged cryptococci.. PLoS One, 5(12), e15968.
- The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation.. Proc Natl Acad Sci U S A, 106(31), 12980-12985.
- Arp2/3 complex activity in filopodia of spreading cells.. BMC Cell Biol, 9, 65.
- MIM: a multifunctional scaffold protein.. J Mol Med (Berl), 85(6), 569-576.
- N-WASP involvement in dorsal ruffle formation in mouse embryonic fibroblasts.. Mol Biol Cell, 18(2), 678-687.
- Exploring the role of E. faecalis enterococcal polysaccharide antigen (
EPA ) and lipoproteins in evasion of phagocytosis. Molecular Microbiology.
- Altered Macrophage Polarization Induces Experimental Pulmonary Hypertension and Is Observed in Patients With Pulmonary Arterial Hypertension. Arteriosclerosis, Thrombosis, and Vascular Biology.
- Correction: 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection. PLOS Pathogens, 16(11), e1009058-e1009058.
- Neutrophils use selective autophagy receptor p62/SQSTM1 to target Staphylococcus aureus for degradation in vivo in zebrafish.
- The autophagic response toStaphylococcus aureusprovides an intracellular niche in neutrophils.
- Dissemination of Cryptococcus neoformans via localised proliferation and blockage of blood vessels.
- The mouse lung early cellular innate immune response is not sufficient to control fungal infection with Cryptococcus neoformans.
Chapters
- Zebrafish Larvae as an Experimental Model of Cryptococcal Meningitis, Methods in Molecular Biology (pp. 47-69). Springer US
- Intracellular Replication and Exit Strategies, Cryptococcus (pp. 441-450). ASM Press
Conference proceedings papers
- Multi-class Image Segmentation in Fluorescence Microscopy Using Polytrees (pp 517-528) View this article in WRRO
Preprints
- Exploring the role ofE. faecalisEnterococcal Polysaccharide Antigen (EPA) and lipoproteins in evasion of phagocytosis, Cold Spring Harbor Laboratory.
- Exploring the role of E. faecalis Enterococcal Polysaccharide Antigen (EPA) and lipoproteins in evasion of phagocytosis, Authorea, Inc..
- Candida albicanssuppression of neutrophil reactive nitrogen species is rescued by host Hif-1αin vivo, Cold Spring Harbor Laboratory.
- Ageing-related defects in macrophage function are driven byMYCandUSF1transcriptional programmes, Cold Spring Harbor Laboratory.
- Candida albicanscells lacking AP-2 have defective hyphae and are avirulent despite increased host uptake and intracellular proliferation in macrophages, Cold Spring Harbor Laboratory.
- An in vitro model to study the naïve human peripheral blood mononuclear cell response to Cryptococcus neoformans infection, Cold Spring Harbor Laboratory.
- Blood vessel occlusion byCryptococcus neoformansis a mechanism for haemorrhagic dissemination of infection, Cold Spring Harbor Laboratory.
- Redistribution of a glucuronoxylomannan epitope towards the capsule surface coincides with Titanisation in the human fungal pathogenCryptococcus neoformans, Cold Spring Harbor Laboratory.
- Alternative oxidase induction protects Candida albicans from respiratory stress and promotes hyphal growth, Cold Spring Harbor Laboratory.
- Inhibition of classical and alternative modes of respiration in C. albicans leads to cell wall remodelling and increased macrophage recognition, Cold Spring Harbor Laboratory.
- A transgenic zebrafish model for the in vivo study of the blood and choroid plexus brain barriers using claudin 5, Cold Spring Harbor Laboratory.
- Mycophenolate mofetil increases inflammation resolution in zebrafish via neutrophil apoptosis, Cold Spring Harbor Laboratory.
- Mycophenolate mofetil increases susceptibility to opportunistic fungal infection independent of lymphocytes, Cold Spring Harbor Laboratory.
- 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection, Cold Spring Harbor Laboratory.
- 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection. PLoS Pathogens, 15(3). View this article in WRRO