skip to primary navigationskip to content
 

Dr Gavin Wright

Research Interests

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 egg Izumo receptor and is essential for mammalian fertilization.
Nature. 2014 Apr 24;508(7497):483-7. doi: 10.1038/nature13203. Epub 2014 Apr 16. PMID: 24739963
Wanaguru M, Liu W, Hahn BH, Rayner JC, Wright GJ. RH5-Basigin interaction plays a major role in the host tropism of Plasmodium falciparum. Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20735-40. doi: 10.1073/pnas.1320771110. Epub 2013 Dec 2.
PMID: 24297912
 
Powell GT, Wright GJ. Jamb and jamc are essential for vertebrate myocyte fusion. PLoS Biol. 2011 Dec;9(12):e1001216. doi: 10.1371/journal.pbio.1001216. Epub 2011 Dec 13. PMID: 22180726
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 Nov 9;480(7378):534-7. doi: 10.1038/nature10606. PMID: 22080952
 
Bushell KM, Söllner C, Schuster-Boeckler B, Bateman A, Wright GJ. Large-scale screening for novel low-affinity extracellular protein interactions. Genome Res. 2008 Apr;18(4):622-30. doi: 10.1101/gr.7187808. Epub 2008 Feb 22. PMID: 18296487
 
Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH, Barclay AN. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity. 2000 Aug;13(2):233-42. PMID: 10981966