Workpackage 1

The development of new assays to investigate death-inducing protein complexes and to identify small molecule regulators of these complexes. This research will generate a new understanding of cell death-inducing protein complexes and enable screening approaches that form workpackage 2.

Workpackage 2

The screening of unique natural product libraries with new high-throughput assays that measure the formation of cell-death inducing protein complexes.

Compounds that either activate or inhibit complex formation are of interest and such compounds will become bio-tools for the cell-death research community and potential lead compounds for development as therapeutics for cancer, inflammatory diseases and other pathologies.

Workpackage 3

The purification and structure elucidation of bio-active chemicals from natural product extracts.

Workpackage 4

The development of new models of protein:protein interactions in the apoptosome and necrosome to identify pharmacophores that block or mimic protein-protein interactions as well as drug:protein interactions.

Peptidomimetics based on these predictions will be synthesized and tested using the new assays emerging from WP1. This will also deliver training in virtual screening and chemo-informatic tools used to identify, analyse and optimize drug-like molecules.