Understanding the proteins that regulate programmed cell death at the molecular level

Understanding the proteins that regulate programmed cell death at the molecular level

 

Project details

Apoptosis is the principle pathway that targets cells for programmed death and is required for removal of faulty cells, for example due to viral infection or cancer. Defective cell death can contribute to disease in a variety of settings including cancers, heart attack, stroke or degenerative disease (Moldoveanu and Czabotar, Cold Spring Harbour Perpec Biol 2020 vol 12).

We are interested in understanding how the pro-apoptotic protein Bax, a member of the BCL-2 family, promotes apoptosis. To understand this we will characterise 3‑D structures of Bax using X-ray crystallography and CryoEM. In addition we will characterise binding of ligands to Bax using a combination of structural and biophysical techniques.

The project will suit students interested in protein crystallography, structural biology, drug discovery and protein-ligand interactions.

About our research group

The Czabotar lab is situated in the Institute’s Structural Biology division. Our research focuses on using X-ray crystallography, CryoEM and other biophysical techniques to understand the processes involved in targeted cell death (eg Czabotar, Cell 2013 152:519-31). We aim to exploit high resolution structural information obtained by crystal structures to guide development of novel therapies for diseases characterized by cell death and to understand resistance mechanisms to drugs targeting the family members eg Venetoclax (Birkinshaw Nature Communication 2018 vol 10 p2835).

 

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