Structure function studies of the Pyrin inflammasome

Structure function studies of the Pyrin inflammasome

Project details

We recently identified a new disease caused by a mutation in the innate immune receptor Pyrin, which results in a severe chronic inflammation (Masters et al, Sci Trans Med 2016). This mutation increases the activation of the Pyrin “inflammasome”, a protein complex that produces the cytokine IL-1b. Therefore the patients have now been treated by blocking IL-1b.

In this project we will study the three dimensional structure of Pyrin in its inactive and active confirmations. This will involve protein biochemistry techniques for modifications and purification, followed by structural analysis by SAXS, CryoEM and crystalisation. Based on these results we will perform additional functional studies to confirm the basis for Pyrin activation, with relevance for chronic inflammatory diseases, and infectious pathogens that trigger the Pyrin inflammasome.

 

About our research group

This project is a collaborative effort between the Institute and the University of Bonn, supported by the Bonn & Melbourne Research and Graduate training group (Bo&merang). 
The student will perform two years research in the laboratory of Dr Seth Masters at the Walter and Eliza Hall Institute, and one year in the laboratory of Dr Matthias Geyer at the University of Bonn, Germany.

The Masters laboratory studies innate immunity based on investigations of genetic changes that result in inflammatory diseases. This is mostly focused around a family of innate immune receptors that can form inflammasome complexes and trigger production of the potent inflammatory cytokine IL-1b.

The Geyer lab is interested in the molecular mechanisms that govern immune receptor activation. This incorporates a variety of techniques from molecular biology and biochemistry to structural biology to analyse interaction between proteins, RNA, lipids, and ligands. 

 

Researchers:

Dr Seth Masters

Seth Masters
Dr
Seth
Masters
Laboratory Head
Professor Matthias Geyer profile shot
Professor
Matthias
Geyer
University of Bonn

Project Type:

Dr Seth Masters in a lab

The mystery of a rare, debilitating disease that has afflicted generations of European families – and long baffled their doctors – has been solved.