Regulating the mitochondrial pathway of apoptosis
Project type
Honours
| Supervisor(s) | Division | |
| (Primary) | Molecular Genetics of Cancer | .(JavaScript must be enabled to view this email address) |
Dr Amber Alsop (Co-supervisor) |
Molecular Genetics of Cancer | .(JavaScript must be enabled to view this email address) |
Details of project
The decisive step for a cell to die by apoptosis involves self-association of the Bcl-2 family members Bak and Bax to form the “apoptotic pore” in mitochondria. In turn, this critical step can be blocked by pro-survival proteins such as Bcl-2 and Mcl-1, yet how they do so remains unclear.
This project will investigate how and when Bak and Bax bind to prosurvival proteins in cells that are dying or that are blocked from dying. Understanding these complexes will help design and target drugs that can initiate apoptosis in cancer cells. Techniques employed will include DNA cloning, PCR mutagenesis, mammalian cell culture (retroviral infection, death assays), western blotting, immunoprecipitation.
Project references
- Dewson G, Kratina T, Czabotar P, Day CL, Adams JM, Kluck RM. Bak activation for apoptosis involves oligomerization of dimers via their alpha6 helices. Mol Cell. 2009 36(4):696-703.
- Dewson G, Kratina T, Sim HW, Puthalakath H, Adams JM, Colman PM et al. To trigger apoptosis Bak exposes its BH3 domain and homo-dimerizes via BH3:grooove interactions. Mol Cell. 2008 30(3):369-380.
- Westphal D, Dewson G, Czabotar PE, Kluck RM. Molecular biology of Bax and Bak activation and action. Biochim Biophys Acta. 2011 1813(4):521-31.
Research interests
Our research focuses on two Bcl-2 protein family members, Bak and Bax, that kill cells by damaging mitochondria. We aim to characterise how Bak and Bax kill cells, by using a range of cell biology, biochemical and structural approaches. Ascertaining how Bax and Bak permeabilise the outer membrane, and how permeability is regulated by other Bcl-2 family proteins such as Bcl-2 and Mcl-1, is important for the development of anti-cancer agents based on the Bcl-2 family of proteins.
Research theme
Cancer
Scientific discipline
- Biochemistry
- Cell Biology
- Molecular Biology
Keywords
apoptosis, mitochondria, Bcl-2 proteins, cancer, Bak, Mcl-1