Understanding resistance to apoptotic cell death

Understanding resistance to apoptotic cell death

Project details

Failure of cells to undergo apoptotic cell death contributes to oncogenesis and to resistance to cancer treatments. A key event in apoptotic cell death is the oligomerisation of the Bak and Bax proteins to form pores in mitochondria, although this step can be blocked by binding of the prosurvival Bcl-2 family members. In addition, we also found that cells lacking PACS1 are resistant to apoptosis due to unusual complexes of Bak and Bax (Brasacchio et al, Cell Death Differ 2017, 24:961).  

This project will characterise Bak and Bax complexes that cause resistance to apoptosis, and so identify ways of circumventing chemoresistance in cancer cells. The project will involve a range of biochemical approaches including cell culture, molecular cloning and flow cytometry (Alsop et al, Nat Comm 2015,  6:6841).

 

About our research group

When apoptotic cell death goes wrong, the results are often cancer or autoimmune diseases. Our laboratory aims to illuminate critical "black boxes" in the apoptotic pathway. We focus how the killer Bak and Bax proteins irreversibly commit cells to die, and how these proteins are regulated. Understanding this process is critical to developing new treatments that either enhance or block apoptosis in diseased cells. Our research program uses biochemical, cell biological and structural approaches to examine Bak and Bax regulation (reviewed in Westphal et al, Biochim Biophys Acta 2011, 813:521). 

 

Researchers:

Dr Ruth Kluck

Ruth
Dr
Ruth
Kluck
Laboratory Head
Dr Amber Alsop profile photo
Dr
Amber
Alsop
Molecular Genetics of Cancer division
Dr Rachel Uren prophile image
Dr
Rachel
Uren
Molecular Genetics of Cancer division

Project Type: