We collaborate widely with scientists and clinicians to advanced proteomics technologies to identify and quantify proteins in cells and biofluids.
Our laboratory covers diverse range of areas that can be categorised into five key focus areas:
A/Prof Andrew Webb is Head of the Colonial Foundation Healthy Ageing Centre.
Australia, Monash University, BSc (MSc)
Australia, Monash University, PhD
Nachbur U, Stafford C, Bankovacki A, Zhan Y, Lindqvist L, Fiil B, Khakam Y, Ko HJ, Sandow J, Falk H, Holien J, Chau D, Hildebrand J, Vince J, Sharp P, Webb AI, Jackman K, Mühlen S, Kennedy C, Lowes K, Murphy J, Hansen MG, Parker M, Hartland E, Lew A, Huang D, Lessene G, and Silke J. A novel RIPK2 inhibitor delays NOD signalling complex formation yet prevents inflammatory cytokine production. Nature Communications. Accepted Jan 2015.
Hildebrand JM, Tanzer MC, Lucet IS, Young SN, Spall SK, Sharma P, Pierotti C, Garnier JM, Dobson RC, Webb AI, Tripaydonis A, Babon JJ, Mulcair MD, Scanlon MJ, Alexander WS, Wilks AF, Czabotar PE, Lessene G, Murphy JM, Silke J. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proceedings of the National Academy of Sciences. 111,42,15072-15077, 2014. PMID: 25288762
Wong W*, Webb AI*, Olshina MA, Infusini G, Tan YH, Hanssen E, Catimel B, Suarez C, Condron M, Angrisano F, Nebi T, Kovar DR, Baum J. A Mechanism for Actin Filament Severing by Malaria Parasite Actin Depolymerizing Factor 1 via a Low Affinity Binding Interface. Journal of Biological Chemistry. 289,7,4043-4054, 2014. PMID: 24371134
Chambers JM, Lindqvist LM, Webb AI, Huang DC, Savage GP, Rizzacasa MA. Synthesis of biotinylated Episilvestrol: highly selective targeting of the translation factors eIF4AI/II. Organic letters. 15,6,1406-1409, 2013. PMID: 23461621
Etemadi N, Webb AI, Bankovacki A, Silke J, Nachbur U. Progranulin does not inhibit TNF and lymphotoxin-α signalling through TNF receptor 1. Immunology and cell biology. 91(10) 661-4, 2013. PMID: 24100384
Pearson JS, Giogha C, Ong SY, Kennedy CL, Kelly M, Robinson KS, Lung TW, Mansell A, Riedmaier P, Oates CV, Zaid A, Mühlen S, Crepin VF, Marches O, Ang CS, Williamson NA, O’Reilly LA, Bankovacki A, Nachbur U, Infusini G, Webb AI, Silke J, Strasser A, Frankel G, Hartland EL. A type III effector antagonizes death receptor signalling during bacterial gut infection, Nature, 501,7466,247-251, 2013. PMID: 24025841
Murphy JM, Czabotar PE, Hildebrand JM, Lucet IS, Zhang JG, Alvarez-Diaz S, Lewis R, Lalaoui N, Metcalf D, Webb AI, Young SN, Varghese LN, Tannahill GM, Hatchell EC, Majewski IJ, Okamoto T, Dobson RC, Hilton DJ, Babon JJ, Nicola NA, Strasser A, Silke J, Alexander WS., The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism, Immunity, 39,3,443-453, 2013. PMID: 24012422
Dejnirattisai W*, Webb AI*, Chan V, Jumnainsong A, Davidson A, Mongkolsapaya J, Screaton G. Lectin switching during dengue virus infection. Journal of Infectious Diseases. 203,12,1775-1783, 2011. PMID: 21606536
Gerlach B*, Cordier SM*, Schmukle AC*, Emmerich CH*, Rieser E*, Haas TL*, Webb AI*, Rickard JA, Anderton H, Wong WW, Nachbur U, Gangoda L, Warnken U, Purcell AW, Silke J, Walczak H. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 471,7340,591-596, 2011. PMID: 21455173
Theodossis A1, Guillonneau C, Welland A, Ely LK, Clements CS, Williamson NA, Webb AI, Wilce JA, Mulder RJ, Dunstone MA, Doherty PC, McCluskey J, Purcell AW, Turner SJ, Rossjohn J. Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition. Proceedings of the National Academy of Sciences. 107,12,5534-5539, 2010. PMID: 20212169
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
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
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 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, 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