Do membrane forces govern assembly of the deadly apoptotic pore?

Do membrane forces govern assembly of the deadly apoptotic pore?

Project details

The goal of this project is to determine how the apoptotic pore forming proteins (BAK and BAX) cluster on the outer membrane of mitochondria. We understand that BAK and BAX form symmetric homodimers and that these dimers form higher-order clusters leading to the formation of the apopotic pore. In the absence of a dominant protein-protein interface between dimers (Uren, eLife 2017 Feb 6;6:e19944; Uren, Philos Trans R Soc Lond B Biol Sci 2017; 372(1726):20160218), we hypothesise that membrane forces drive the association of dimers into clusters during apoptosis.  

We will test this hypothesis using established biochemical techniques (cell culture, protein gel electrophoresis, western blot) in addition to cutting-edge quantitative live cell microscopy techniques in collaboration with the WEHI Centre for Dynamic Imaging. 

About our research group

The Kluck lab investigates how cells die via a process called apoptosis - a normal process that helps remove excess or damaged cells. When apoptotic cell death goes wrong, the results are often cancer or autoimmune diseases.  

We are interested in the proteins inside cells that orchestrate apoptosis, in particular how two pore-forming BCL-2 family members, BAX and BAK, undergo a major conformation change to generate homo-oligomers that generate pores in the mitochondrial outer membrane.  

The overall goal of our research is to identify new means of specifically regulating apoptotic cell death in cancer and other diseases. 

 

Email supervisors

 

Researchers:

Dr Rachel Uren prophile image
Dr
Rachel
Uren
Blood Cells and Blood Cancer division

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