Chemical probing to identify effectors of necroptotic cell death

Chemical probing to identify effectors of necroptotic cell death

Project details

Several tissue inflammatory diseases have been linked to a dysregulation of necroptosis, a regulated form of cell death (Sun, Trends Biochem. Sci. 2014 39:587). This highlights the importance of necroptosis and its promising role as a therapeutic target in the treatment of multiple diseases. 

Necroptosis is triggered by a well-orchestrated signalling cascade involving the kinase RIPK3 and its substrate MLKL, but further effectors remain to be elucidated. We recently identified small molecule inhibitors of necroptotic signalling.

The aim of this project is to design and synthesise chemical probes of these inhibitors and to use them to identify their targets, validate these as necroptotic effectors. Organic synthesis will be a major component of this research, as well as biochemical and cell biology techniques.

 

About our research group

Our lab has a strong focus on medicinal chemistry and chemical biology, and we strive to integrate multi-disciplinary approaches based on cohesive teams of researchers. To achieve this goal, we collaborate widely across the Institute, and all our projects are run as multidisciplinary collegial teams.

In collaboration with colleagues including Dr James Murphy and Professor John Silke, we are developing a range of chemical probes that modulate necroptosis, a programmed form of cellular necrosis. Most of the intricacies of this pathway are still unknown, so we aim to use our chemical probes to identify new protein components of this pathway, and to employ the most advanced compounds to validate necroptosis inhibition in inflammatory diseases.

 

Project schematic
Chemical probes will be used to identify new effectors of necroptosis

 

Researchers:

Dr Christoph Grohmann profile shot
Dr
Christoph
Grohmann
ACRF Chemical Biology division

Project Type: