TNF and IFN signalling

Inflammation is the driving force for several diseases, including rheumatoid arthritis, and is believed to contribute to the severity of other diseases including cancer. Although these pro-inflammatory cytokines have been extensively studied, the roles of tumour necrosis factor (TNF) and interferon-γ (IFNγ) in healthy and disease states remains to be fully elucidated. Using proteomics techniques developed specifically for this project, we are defining the molecular mechanisms regulating cellular responses to TNF and IFNγ, and identifying new components and mechanisms of cytokine signaling signalling.

Collaborators: Dr. Ueli Nachbar and Maria Tanzer, Silke Laboratory; Hartland Laboratory, The University of Melbourne

Necroptosis signalling

The identification of MLKL as the likely final kill switch in the necroptosis signalling cascade has led to enormous interested into its mechanism of action. Using established strategies (SILAC and Enrichment Analysis) and implementing new methodologies (Hydrogen Deuterium Exchange, HDX, and covalent cross-linking) we aim to comprehensively characterise the biological function of MLKL.

Collaborators: Dr Joanne Hildebrand, Silke Laboratory; Dr James Murphy

SOCS5 function

In stark contrast to SOCS1, 2 and 3, a clear biological role for the highly evolutionarily conserved SOCS5 protein has remained elusive. We are interested in identifying and characterising the endogenous protein interactors of SOCS5 through the use SILAC coupled pull downs, cross-linking analysis and phosphoproteomic profiling.

Collaborators: Professor Nic Nicola, Edmond Linossi, Nicholson Laboratory