Grant: Discovery Grants Program - Individual

The control of life and death is as crucial as any question in biology. The survival and growth of cells are controlled by mechanisms that interpret signals from both inside and outside the cell to alter its activity. Over recent years, the processes that control cell death have become very well understood. More recently, the cellular functions that help cells live and grow are being recognised as interdependent. In our laboratory, we study the common fruit fly, the genes of which are far more similar to humans than we once thought. It is an ideal model organism to study this aspect of cell biology. Before opening my lab, I demonstrated that extremely reduced levels of akt a target protein of the insulin receptor, result in cell death throughout the embryonic fruit fly. Since then we have found that a target of akt, foxo, is key in the interpretation of low levels of insulin receptor signalling and acts to inhibit growth and alter metabolism in fruit flies. Most importantly, we have found that foxo may provide a limited survival mechanism during conditions of starvation when nutrients are unavailable. Curiously, foxo may have an important role in sensing the availability of nutrition. In addition, we are investigating other components of insulin receptor signalling including the Down Syndrome gene, minibrain, in flies. In the future, we will identify additional targets of akt, minibrain and foxo and evaluate their roles in cell survival and growth. As cell death plays a role in degeneration of neurons, we investigate the cellular basis of protein induced neurodegeneration in flies. We are studying the effect of the parkin and Pink1, two genes that are defective in some inherited forms of Parkinson disease, in the counteraction of cell death induced by toxic proteins. By increasing the activity of these genes, we have been able to prevent these defects. We are striving to fully understand the biological effects of this process. In summary, our research into the molecular cell biology of fruit flies provides a great opportunity to explore the mechanisms that control the delicate balance between life and death.