Structural Biology of Inflammation

Project description

Description
My laboratory utilises structural biology methods to investigate the structure and function of protein and protein-nucleic acid complexes important in inflammation and cancer. Students undertaking this project will learn a variety of experimental techniques and obtain expertise in protein chemistry, biochemistry and structural biology/cryo-EM, while contributing to research which will lead to new knowledge required for therapeutic designs. It is anticipated students will generate data that will contribute to manuscripts suitable for publication.

Inflammation
An important part of innate immunity is the ability of infected cells to sense and respond to infections by eliciting pro-inflammatory processes. Inflammasomes are key cytoplasmic sensors that detect pathogen components to undergo conversion from inactive to active signalling inflammasomes to drive inflammatory signalling. The activation status of inflammasomes is under tight-regulations to maintain healthy homeostasis, but mutations in inflammasome components can result in imbalance of inflammatory signalling which is the underlying basis of many autoinflammatory diseases. Our interest is focused on understanding how the activity of inflammasome is controlled and the mechanisms by which inflammasome sensors detect infections and the molecular details of inflammasome activation.

In this project, the student will investigate the AIM2 inflammasome sensor and its binding with interacting partners and characterise the role of these interactions in AIM2 inflammasome activation. Specific aims will include characterisation on the mechanism of AIM2 oligomerisation and recruitment of core components of the inflammasome including ASC and caspase1 to form signalling inflammasome. Students will use protein expression and purification, functional biochemistry and structural biology method (cryo-EM) to understand AIM2 inflammasome signalling.

Selected publications:
– Wong W*, Huang R*, Menant S, Hong C, Sandow JJ, Birkinshaw RW, Healer J, Hodder AN, Kanjee U, Tonkin CJ, Heckmann D, Soroka V, Sogaard TMM, Jorgensen T, Duraisingh MT, Czabotar PE, Jongh WAd, Tham WH, Webb AI, Yu Z, Cowman AF. (2019) Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex, Nature. 565: 118-121. *co-first author
– Wong W*, Bai XC*, Sleeb BE*, Triglia T*, Brown A, Thompson JK, Jackson KE, Hanssen E, Marapana DS, Fernandez IS, Ralph SA, Cowman AF, Scheres SHW, Baum J. (2017) Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis. Nature Microbiology 2 Article number: 17031. *co-first author
– Wong W*, Bai XC*, Brown A*, Fernandez IS, Hanssen E, Condron M, Tan YH, Baum J, Scheres SH. (2014) Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine eLife 3 – P12695994, *co-first author