Grant: Operating Grant

Programmed cell death or apoptosis normally prevents cells that have lost growth control from going on to form tumours. During apoptosis, holes are formed in the membranes inside of cells, causing cells to die. Chemotherapy kills cancer cells by causing apoptosis, and certain gene products including the protein Bcl-2 inhibit this process; expression of Bcl-2 in cancer causes resistance to treatment. We have discovered that Bcl-2 prevents the formation of holes in membranes by changing its shape after it becomes attached to the membrane. In this new shape, Bcl-2 binds and inhibits other proteins that make the holes in the membrane. We will use new techniques in biophysics to study exactly how holes are formed and how Bcl-2 and other proteins control the formation of these holes inside cancer cells. Understanding how formation of holes in membranes is regulated will advance treatment options currently being explored with Bcl-2 inhibitors and is expected to open up new possibilities for cancer treatment.