Research
Despite extracellular adaptive and innate immunity, viral and bacterial pathogens are still able to infect cells. Because of this there must be a way to neutralise pathogens once they are inside the cell. Historically, infected cells have been seen as largely helpless and only able to signal for help. However, there is increasing evidence that cells have their own mechanisms for directly restricting pathogen replication. It is this process of intracellular immunity that my lab is interested in.
In order to study intracellular immunity, we combine in vivo and in vitro pathogen infection experiments with structural and biophysical approaches. Using these techniques we are attempting to address how the host targets fast evolving pathogens and the different mechanisms that are employed to neutralise them.
Publications
Intracellular sensing of complement C3 activates cell autonomous immunity (2014) Jerry C. H. Tam, Susanna R. Bidgood, William A. McEwan, Leo C. James Science 2014: Vol. 345 no. 6201
Vaysburd M, Watkinson RE, Cooper H, Reed M, O'Connell K, Smith J, Cruickshanks J, James LC. (2013) Intracellular antibody receptor TRIM21 prevents fatal viral infection. Proc Natl Acad Sci U S A. ;110(30):12397-401.
Randow F, MacMicking JD, James LC.(2013) Cellular self-defense: how cell-autonomous immunity protects against pathogens. Science. 340(6133):701-6.
McEwan WA, Tam JC, Watkinson RE, Bidgood SR, Mallery DL, James LC (2013) Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21. Nat Immunol. 14(4):327-36.
Hauler F, Mallery DL, McEwan,WA, Bidgood SR, James LC (2012) AAA ATPase p97/VCP is essential for TRIM21-mediated virus neutralization. Proc Natl Acad Sci U S A. 109(48):19733-8.
Price AJ, Fletcher AJ, Schaller T, Elliott T, Lee K, Kewalramani VN, Chin JW, Towers GJ, James LC (2012) CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication PLoS Pathog. 8, e1002896, doi:10.1371/journal.ppat.1002896.
McEwan WA, Hauler F, Williams CR, Bidgood SR, Mallery DL, Crowther RA, James LC. (2012) Regulation of Virus Neutralization and the Persistent Fraction by TRIM21. J Virol. May 30
Caines ME, Bichel K, Price AJ, McEwan WA, Towers GJ, Willett BJ, Freund SM, James LC. (2012) Diverse HIV viruses are targeted by a conformationally dynamic antiviral. Nat Struct Mol Biol. Mar 11;19(4):411-6
Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC (2010) Antibodies mediate intracellular immunity through TRIM21 Proc Natl Acad Sci USA. 107(46):19985-90
