Emerging from the interface between chemistry and biology, chemical biology has led to the establishment of several game-changing drug discovery paradigms. Among these revolutionary approaches, PROteolysis-TArgeting Chimera(PROTAC) has attracted considerable attention in repurposing broad-spectrum therapeutics to be target-selective degraders. Together with the Payne research group, we are aiming to rationally re-design kinase inhibitors as PROTAC constructs for next-generation precision medicine to treat otherwise intractable cancers and cardiovascular complications.
The Akt kinases are critical regulators of cell physiology but have also been associated with the development of thrombosis, cancer and other biggest killer diseases. This kinase family is composed of three highly homologous isoforms (with 73% sequence similarity): Akt1, Akt2 and Akt3. Gene knockout studies have shown that Akt isoforms have non-overlapping regulatory functions in cell which contribute to their pathological and physiological diversity in vivo. For example, both Akt2 and Akt3 regulate platelet activation in thrombosis, whereas Akt1 knockout mice develop a severe defect in haemostatic plug formation. This observation together with the well-established Akt-isoform signalling in cancer underscore the urgent need of Akt-isoform-specific inhibitors for next-generation precision medicines.
Recently, the revolutionary approaches in drug development termed PROTAC (PROteolysis-TArgeting Chimera) have attracted considerable attention in repurposing broad-spectrum therapeutics to be target-selective degraders. PROTACs are bifunctional molecules capable of binding to a ubiquitinase complex and the protein target simultaneously, thereby promoting selective target degradation. Importantly, rational design of PROTAC constructs has led to isoform-specific degraders to target oncogenic kinases and transcription factors otherwise intractable to functional inhibition.
HDR Inherent Requirements
In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:
- Confidential disclosure and registration of a disability that may hinder your performance in your degree;
- Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
- Ability to perform independently and/or with minimal supervision;
- Ability to undertake certain physical tasks (e.g. heavy lifting);
- Ability to undertake observatory, sensory and communication tasks;
- Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);
- Ability to work in confined spaces or at heights;
- Ability to operate heavy machinery (e.g. farming equipment);
- Hold or acquire an Australian driver’s licence;
- Hold a current scuba diving license;
- Hold a current Working with Children Check;
- Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)
You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.
The opportunity ID for this research opportunity is 2738