Russell Wallis

Structural biology of complement activation

Russel Wallis 2.0

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 Infection, Immunity and Inflammation (III).

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 (III) 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 (III).

The structure of pneumolysin, a pore-forming toxin from Streptococcus pneumoniae
The structure of pneumolysin, a pore-forming toxin from Streptococcus pneumoniae

The interaction between the collagen-like domain of mannan-binding lectin and its associated serine protease, MASP-1
The interaction between the collagen-like domain of mannan-binding lectin and its associated serine protease, MASP-1

Key Publications

Group Members

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

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