Development of fluorescently labeled Bcl-2 inhibitors
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
| (Primary) | Chemical Biology | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Molecular Genetics of Cancer | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Chemical Biology | .(JavaScript must be enabled to view this email address) |
Details of project
Inhibition of the pro-survival Bcl-2 proteins, which act to block programmed cell death, by small molecule inhibitors is a new approach for the treatment of selected cancers. Small molecule inhibitors of these proteins have recently entered clinical trials. These compounds work though inhibition of the activity of the cell death inhibitor Bcl-2 (or its relatives Bcl-xL, Bcl-w) by mimicking its binding interaction with pro-apoptotic BH3-only proteins (such as BIM).
In cells, pro-survival Bcl-2-like proteins exist either free or in complex with pro-apoptotic BH3-only proteins. A simple method to determine the amount of free Bcl-2 in cancer cells would allow identification of those cells (and thus patients) most appropriate for targeting with Bcl-2 inhibitors.
We propose to modify a panel of known Bcl-2 inhibitors with fluorophores to generate cell-permeable fluorescent probes for free Bcl-2 protein. Such compounds will be designed using the known binding mode of these inhibitors to Bcl-2 proteins and will be tested in an array of mammalian cancer cell lines.
Research interests
Our laboratories are engaged in basic research in cancer biology and the development of novel cancer therapeutics. Specifically, Dr Burns (a laboratory head within the Chemical Biology division headed by Professor David Huang) research interests are in the design and synthesis of novel chemical compounds with potent biological activity against targets implicated in cancer. Such compounds have the potential to be further developed as drugs and can also help unravel the complex signaling processes present in cancer cells.
Professor Strasser’s research interests include identification of the signalling pathways that mediate developmentally programmed cell death in mammals and those that are responsible for chemotherapy-induced killing of cancer cells, with the goal to develop improved strategies for treatment of cancer and autoimmune diseases.
Research theme
Cancer
Scientific discipline
- Cell Biology
- Chemistry
Keywords
fluorescent labelling, apoptosis, synthesis