ORCID Profile
0000-0003-0537-0863
Current Organisation
University of York
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Publisher: Public Library of Science (PLoS)
Date: 27-02-2015
Publisher: Springer Science and Business Media LLC
Date: 20-12-2011
DOI: 10.1038/NCOMMS1615
Publisher: eLife Sciences Publications, Ltd
Date: 30-07-2019
Publisher: Public Library of Science (PLoS)
Date: 27-07-2012
Publisher: Cold Spring Harbor Laboratory
Date: 11-08-2022
DOI: 10.1101/2022.08.09.503398
Abstract: Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have been studied extensively in P. falciparum and are hypothesized to have overlapping, but critical roles just prior to host cell entry. The zoonotic malaria parasite, P. knowlesi , has larger invasive merozoites and contains a smaller, less redundant, DBP and RBL repertoire than P. falciparum . One DBP (DBPα) and one RBL, normocyte binding protein Xa (NBPXa) are essential for invasion of human RBCs. Taking advantage of the unique biological features of P. knowlesi and iterative CRISPR-Cas9 genome editing, we determine the precise order of key invasion milestones and demonstrate distinct roles for each family. These distinct roles support a mechanism for phased commitment to invasion and can be targeted synergistically with invasion inhibitory antibodies.
Publisher: eLife Sciences Publications, Ltd
Date: 22-08-2019
DOI: 10.7554/ELIFE.46840
Abstract: The immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor G6b-B is critical for platelet production and activation. Loss of G6b-B results in severe macrothrombocytopenia, myelofibrosis and aberrant platelet function in mice and humans. Using a combination of immunohistochemistry, affinity chromatography and proteomics, we identified the extracellular matrix heparan sulfate (HS) proteoglycan perlecan as a G6b-B binding partner. Subsequent in vitro biochemical studies and a cell-based genetic screen demonstrated that the interaction is specifically mediated by the HS chains of perlecan. Biophysical analysis revealed that heparin forms a high-affinity complex with G6b-B and mediates dimerization. Using platelets from humans and genetically modified mice, we demonstrate that binding of G6b-B to HS and multivalent heparin inhibits platelet and megakaryocyte function by inducing downstream signaling via the tyrosine phosphatases Shp1 and Shp2. Our findings provide novel insights into how G6b-B is regulated and contribute to our understanding of the interaction of megakaryocytes and platelets with glycans.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 30-07-2014
DOI: 10.1126/SCITRANSLMED.3008705
Abstract: Uncharacterized proteins from the merozoite stage of Plasmodium falciparum provide new antigens for malaria blood-stage vaccine development.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 06-2019
Publisher: Springer Science and Business Media LLC
Date: 22-10-2015
Publisher: Public Library of Science (PLoS)
Date: 08-11-2012
Publisher: Elsevier BV
Date: 07-2016
Publisher: Elsevier BV
Date: 2015
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Gavin Wright.