Webb Lab

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

Rheumatic fever

Rheumatic fever has a high incidence in Australian indigenous communities, particularly in children, and if untreated can have serious complications including rheumatic heart disease. Our work is aimed at developing a blood test which will allow us to predict which children are at risk of developing rheumatic fever, so that we can deliver treatment where it is needed most.

Collaborators: Professor Ian Wicks, Professor Liam O’Connor

Gastric cancer

Gastric cancer, one of the world’s most devastating cancers, is a disease that is generally diagnosed at an advanced stage, when there are limited treatment options. Using three of the most relevant models available for intestinal-type gastric cancer, we aim to identify serum biomarkers of gastric cancer and test their validity for human disease.

Collaborators: Dr Tracy Putoczki; Professor Matthias Ernst, Olivia Newton-John Cancer Research Institute

Bak function and conformation

Apoptosis is the fundamental process of programmed cell suicide that is essential for proper development and immune system function. But how the key pro-apoptotic proteins Bak and Bax are restrained, then released to trigger cell death remains unclear. Through the use of the proteomic strategies that have reduced to standard practice in the Proteomics Lab (SILAC and Enrichment Analysis) and the implementation of new methodologies (HDX and cross-linking) we aim to comprehensively characterise the nature of the Bak and Bax apoptotic molecular switches.

Collaborators: Mark Li, Destiny Dalseno, Dr Robert Ninnis, Dr Grant Dewson