Enabling deubiquitinase drug discovery

Enabling deubiquitinase drug discovery

Project details

The ubiquitin proteasome system presents significant untapped potential for drug discovery. Ubiquitination regulates the turnover of proteins, and artificially changing the ubiquitination state of a protein hence enables new ways to regulate protein abundance. Importantly, this concept extends to so-called undruggable targets: activation of E3 ligases (which add ubiquitin), or inhibition of deubiquitinases (aka DUBs, enzymes that remove ubiquitin) represent state-of-the-art concepts in drug discovery.

The Komander lab has recently been involved in some of the very first efforts to specifically target the oncogenic DUB USP7 (Turnbull et al, Nature 2017, 550(7677):481-486), providing proof-of-concept that DUBs are viable drug targets. This protein biochemistry project will entail molecular and structural characterisation of DUB domains, drug discovery, and testing of compounds in available and to-be-established biological systems.

About our research group

The Komander lab is the core of the Institute’s recently established Ubiquitin Signalling division, which is the first-of-its-kind ubiquitin focused research division in Australia. Professor Komander is a world leader in ubiquitination research, with strong interests in unravelling the ubiquitin code, and exploiting ubiquitination in drug discovery.

You will be working in a multi-disciplinary environment within the lab, the division, and Institute, with many layers of support for each part of the project, including support through the National Drug Discovery Centre, and through a network of Australian and global collaborators. Strong links to pharma and biotech industries enable additional perspectives. 

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