WEHI Special ACRF Chemical Biology Seminar hosted by Dr Brad Sleebs
 

Dr Laura Edgington-Mitchell

Head – Protease Pathophysiology Laboratory, Department of Biochemistry & Pharmacology, Bio21 Institute, The University of Melbourne

Application of chemical tools to dissect the pathophysiological roles of proteases

 

Davis Auditorium

Join via TEAMS

Including Q&A session

Proteases are enzymes that cleave peptide bonds within proteins, and this function is critical for a wide range of cellular processes, from digestion and regulation of protein homeostasis to apoptosis and immune function. Aberrant protease activity is a hallmark of many diseases, including cancer, inflammation, neurodegenerative diseases and associated pain. Proteases are thus attractive as targets for both the diagnosis and treatment of these conditions.

As protease activity is tightly controlled at the post-translational level, measures of total protein expression rarely reflect the pool of active, functional protease. We have developed a series of novel chemical tools called activity-based probes (ABPs) that can measure the activity of proteases with high specificity. These tools can be applied to measure protease activity in whole animals by non-invasive imaging, in tissues by ex vivo imaging, and at the cellular level by confocal microscopy and flow cytometry. The major innovation of ABPs is that they covalently modify their protease targets, allowing for careful validation by in-gel fluorescence, immunoprecipitation or activity-based proteomics. In this talk, I will introduce ABPs and give examples of the breadth of their application, particularly with respect to their value as pharmacological tools to support drug discovery (inhibitor development, monitoring of target engagement, target validation, and application to fluorescence-guided surgeries). I will also introduce our refined chemical proteomics platform that allows systematic and unbiased identification of protease substrates in complex samples such as tissue lysates.

Dr Laura Edgington-Mitchell is the Head of the Protease Pathophysiology Lab in the Dept of Biochemistry & Pharmacology at Bio21. Laura’s research program broadly aims to validate proteases as therapeutic targets in cancer and inflammation. Laura has been awarded an NHMRC Peter Doherty Fellowship, Grimwade and ARC DECRA Fellowships. She is also the current Vice President of the International Proteolysis Society.

All welcome!