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Cells behaving badly

Clocktower.

Catherine DayAssociate Professor Catherine Day
"Our ultimate aim is to discover improved ways to treat cancer so that only the tumour cells are killed."

Every second of every day, more than a million cells in our bodies kill themselves as part of a constant replacement policy.

This normal programmed cell death – apoptosis – sees cells activating an inbuilt self-destruct mechanism. The process is critical to our well-being. When it fails, and cells don't die when they should, they accumulate and can turn into cancers.

Current cancer treatments include radiotherapy and chemotherapy. But, while they may destroy rogue cells, they tend to wipe out a great deal more as well and the side effects can be unpleasant. So it would be a giant leap forward if there were more effective drugs that could get cancer cells to do the right thing and undergo apoptosis. For more than a decade, Associate Professor Catherine Day (Department of Biochemistry) has been collaborating on the problem with a team of cell biologists based in Melbourne.

"In order to come up with the kind of drugs we need, it is necessary to understand the mechanisms of cell death at the molecular level," says Day, who specialises in understanding the interactions of proteins. She hopes to discover how to control when proteins interact so that apoptosis can be triggered in the unwanted cells and they then die as they were supposed to do. One way to control apoptosis is to regulate the amount of inhibitory proteins present. These proteins act as brakes and, when present in excess, they contribute to tumour formation.

A regulatory protein called ubiquitin, which binds to other proteins and labels them for destruction, is important. "Right now we are working on understanding how modification of a key inhibitor of apoptosis protein by ubiquitin controls apoptosis," says Day.

"We don't know how addition of ubiquitin to this protein is controlled, but we know it is important and when it goes wrong this contributes to cancer, so we are using protein biochemistry and structural biology to try to understand the process.

"There are already therapeutic compounds that target this protein in trials and we hope that our work will allow better compounds to be developed.

"We're not working from ground zero, but it's still early days. Our ultimate aim is to discover improved ways to treat cancer so that only the tumour cells are killed." Day notes that, without substantial internal and external funding, the programme would have struggled to retain its leading role.

"Constant support from the Marsden Fund has been critical for pretty much everything that we have done. That's really made a difference, because this research depends on having a good team of people as well as access to the right equipment.

"Investment in equipment by the University has really paid off for us. We now have the capacity to work effectively so that we can contribute to international collaborations."

Funding

  • Marsden Fund
  • Lottery Health Research
  • University of Otago