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Cambridge Immunology Network



The Cell surface signalling laboratory is interested in the molecular basis of cellular recognition. Using our technologies, we have shown that it is possible to identify extracellular protein interactions that are essential for cellular processes that are critical for disease pathogenesis. We are currently working on recognition events that are important in malaria, heart disease and fertilization.
The team, headed by Gavin Wright, has developed a screening assay called AVEXIS (AVidity-based EXtracellular Interaction Screen) that overcomes many of the technical problems associated with identifying interactions between receptor proteins. Using this method, the team takes a unique large-scale approach to systematically identify networks of extracellular protein interactions between cells.
The basic rationale is to compile recombinant protein libraries containing the full repertoire of receptor proteins displayed on the surface of known interacting cell types. These receptor proteins are then screened against each other to identify novel interactions. The cellular interactions that we select for study are important for fundamental biological processes or the pathogenesis of disease. Once we have identified the receptor-ligand interactions involved, we aim to determine their role using functional assays.
Taking this approach, we have identified critical receptor interactions that can then be targeted to develop novel therapeutics. Importantly, extracellular protein interactions are amenable to this approach because they are accessible to systemically delivered drugs such as therapeutic antibodies. Currently, the laboratory is focusing on three main cellular interactions:
  • P. falciparum merozoite:Red blood cell - A host-pathogen interaction required for the pathogenesis of malaria.
  • Platelet:Platelet - The cellular interaction responsible for heart disease and stroke, two of the leading causes of human mortality.
  • Sperm:Egg - The cellular interaction responsible for new life. Understanding this could lead to the development of novel contraceptives and fertility treatments.


Key publications: 

Bianchi-E, Doe-B, Goulding-D, Wright-GJ. “Juno is the Izumo egg receptor and is essential for mammalian fertilization.” Nature 2014 508 p483.


Bianchi-E and Wright-GJ. “Cross-species fertilisation: the hamster egg receptor, Juno, binds the human sperm ligand, Izumo1.” Philosophical Transactions B 2015 370 p20140101.


Crosnier-C, Bustamante-LY, Bartholdson-SJ, Bei-AK, Theron-M, Uchikawa-M, Mboup-S, Ndir-O, Kwiatkowski-DP, Duraisingh-MT, Rayner-JC, Wright-GJ. “Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum.” Nature 2011 480 p534.


Wanaguru-M, Liu-W, Hahn-BH, Rayner-JC, Wright-GJ. “The RH5-Basigin interaction plays a major role in the host tropism of Plasmodium falciparum.” PNAS 2013 110 p20735.


Zenonos-ZA, Dummler-SK, Muller-Sienerth-N, Chen-J, Preiser-PR, Rayner-JC, Wright-GJ. “Basigin is a druggable target for host-oriented anti-malarial interventions.” Journal of Experimental Medicine 2015 212 p1145.


Galaway-F, Drought-LG, Fala-M, Cross-N, Kemp-AC, Rayner-JC, Wright-GJ. “P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5.” Nature Communications 2017 8 p14333.


Douglas-AD, Baldeviano-GC, Lucas-CM, Lugo-Roman-LA, Crosnier-C, Bartholdson-SJ, Diouf-A, Miura-K, Lambert-LE, Ventocilla-JA, Leiva-KP, Milne-KH, Illingworth-JJ, Spencer-AJ, Hjerrild-KA, Alanine-DG, Turner-AV, Moorhead-JT, Edgel-KA, Wu-Y, Long-CA, Wright-GJ, Lescano-AG, Draper-SJ. “A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in Aotus monkeys.” Cell Host Microbe 2015 14 p130.


Bartholdson-SJ, Bustamante-LY, Crosnier-C, Johnson-S, Lea-S, Rayner-JC, Wright-GJ. "Semaphorin-7A is an Erythrocyte Receptor for P. falciparum Merozoite-Specific TRAP Homolog, MTRAP." PLoS Pathogens 2012 8 e1003031.


Crosnier-C, Wanaguru-M, McDade-B, Osier-FH, Marsh-K, Rayner-JC, Wright-GJ. “A library of functional recombinant cell-surface and secreted P. falciparum merozoite proteins.” Molecular and Cellular Proteomics 2013 12 p3976.


Crosnier-C, Iqbal-Z, Knuepfer-E, Maciuca-S, Perrin-AJ, Kamuyu-G, Goulding-D, Bustamante-LY, Miles-A, Moore-SC, Dougan-G, Holder-AA, Kwiatkowski-DP, Rayner-JC, Pleass-RJ, Wright-GJ. "Binding of Plasmodium falciparum merozoite surface proteins DBLMSP and DBLMSP2 to human Immunoglobulin M is conserved among broadly diverged sequence variants." Journal of Biological Chemistry 2016 291 p14285.


Wanaguru-M, Crosnier-C, Johnson-S, Rayner-JC, Wright-GJ. “A biochemical analysis of the Plasmodium falciparum Erythrocyte Binding Antigen-175 (EBA175): Glycophorin-A interaction: implications for vaccine design.” Journal of Biological Chemistry 2013 288 p32106.


Dundas-K, Shears-MJ, Sun-Y, Hopp-CS, Crosnier-C, Metcalf-T, Girling-G, Sinnis-P, Billker-O, Wright-GJ. “Alpha-v-containing integrins are host receptors for the Plasmodium falciparum sporozoite surface protein, TRAP.” PNAS 2018 115 p4477.


Wright-GJ, Puklavec-MJ, Willis-AC, Hoek-RM, Sedgwick-JD, Brown-MH and Barclay-AN. “Lymphoid/neuronal cell surface OX2 glycoprotein recognises a novel receptor on macrophages implicated in the control of their function.” Immunity. 13 2000 p233.


Hoek-RM, Ruuls-SR, Murphy-CA, Wright-GJ, Goddard-R, Zurawski-SM, Blom-B, Homola-ME, Streit-WJ, Brown-MH, Barclay-AN, Sedgwick-JD. “Down-regulation of the macrophage lineage through interaction with OX2 (CD200).” Science. 290 2000 p1768.


Powell-GT and Wright-GJ. “Jamb and jamc are essential for vertebrate myocyte fusion.” PLoS Biology 2011 9 e1001216.


Söllner-C and Wright-GJ. “A cell surface interaction network of neural leucine-rich repeat receptors.” Genome Biology 2009 10 R99.


Wright-GJ†, Leslie-JD†, Ariza-McNaughton-L and Lewis-J. “Delta proteins and MAGI proteins: an interaction of Notch ligands with intracellular scaffolding molecules and its significance for zebrafish development.” Development 131 2004 p5659.


Bushell-KM, Söllner-C, Schuster-Boeckler-B, Bateman-A, Wright-GJ. “Large-scale screening for novel low-affinity extracellular protein interactions.” Genome Research 2008 18 p622.


Sharma-S, Bartholdson-SJ, Couch-A, Yusa-K, Wright-GJ. “Genome-scale identification of cellular pathways required for cell surface recognition.” Genome Research 2018 28 p1372.


Sun-Y, Vandenbriele-C, Kauskot-A, Verhamme-P, Hoylaerts-MF, Wright-GJ. “A human platelet receptor protein microarray identifies FcεR1α as an activating PEAR1 ligand.” Molecular and Cellular Proteomics 2015 14 p1265.


Dr Gavin  Wright
Not available for consultancy


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