Leicester Institute of Structural and Chemical Biology

Russell Wallis

Structural biology of complement activation

Research summary

Our research aims to understand how mammalian hosts defend themselves against pathogenic microorganisms, with a particular focus on a reaction cascade called complement. Complement activates as soon as a pathogen enters the body and serves to neutralise the threat via lysis or opsonisation (where the pathogen is tagged for destruction by host phagocytic cells) and prepare the body against further assault by stimulating and directing inflammatory and adaptive immune responses. Defective complement activation is associated with a wide range of diseases including immunodeficiences, inflammatory disorders (e.g. lupus erythematosus and rheumatoid arthritis), transplant rejection, and ischaemic diseases e.g. of the heart, kidney and brain.

Our research is focused on understanding four main aspects of complement activation at the molecular level: how complement components are able to distinguish between self and non- or altered-self structures; how binding to these structures initiates complement activation; how complement regulators control activation and prevent damage to host tissues and how mutations to complement components lead to disease. Our strategy is to characterise the protein-protein and protein carbohydrate interactions of complement using structural biology (X-ray crystallography, SAXS and EM) and biophysical methods (e.g. ITC, surface plasmon resonance, analytical ultracentrifugation and fluorescence). Our work is carried out in collaboration with Professors Peter Moody (LISCB) and Wilhelm Schwaeble, Department of Respiratory Sciences.

In addition to our work on complement activation, we are also interested in other host-pathogen interactions associated with disease, including the mechanism of action of the pore forming toxin, pnemolysin, of Streptococcus pneumoniae, with Professor Peter Andrew (Respiratory Sciences) and Dr Andrew Hudson (LISCB) and enzymes and signalling pathways of Mycobacterium tuberculosis and Gram +ve bacteria, with Drs Helen O’Hare, Galina Mukamolova, Ed Galyov and Hasan Yesilkaya (Respiratory Sciences).

Key publications

Group members

Ahmad Alzamami, Luay Al-Kanan, Jamal Almitairi, Farah Badakshi, Baleeg Kadhim (with Galina Mukamolova) and Zac Newland-Smith (with Helen O’Hare).

See Russell Wallis's staff page.

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