Grant: Discovery Grants Program - Individual

The normal development and survival of animals require that some of their cells undergo a form of cellular suicide, termed programmed cell death. For example, during development, fingers are formed when the cells between the fingers die via programmed cell death. The Bell laboratory has discovered and continues to lead investigations into a new pathway of programmed cell death, termed the TAF6delta  pathway. The TAF6delta  pathway differs from known pathways of cell death in several important respects. These include its ability to kill cells in the absence of a central suicide protein known as p53, and, more importantly, the fact that the gene that encodes TAF6 is essential to cell survival, whereas those of other known cell death proteins are not. Here, we propose a research program to better understand how cells are able to interpret their environment to decide whether to undergo suicide or continue to live, using the TAF6 pathway as a model. We propose to answer three research questions. 1) Firstly, we know TAF6 is cleaved by cellular enzymes during cell death. We will ask whether or not this cleavage functions to accelerate or potentially slow down the cell death process. 2) Secondly, we will dissect the molecular responsible for turning on the TAF6delta  pathway. We will identify cellular proteins that control TAF6delta  expression using a powerful analytical technique called mass spectrometry. 3) Thirdly, we will determine where in the body TAF6delta  is expressed, using both experimental and computational methods. The outcome of our research will be to shed further light on the TAF6delta  pathway and its impact on cell death. Better understanding cell death pathways has far-reaching applications in biomedicine and biotechnology. Concretely, several disease states, including neurodegenerative disorders such as Alzheimer's disease and cancer, result from uncontrolled cell death. Moreover, the control of cell death has potential applications in ecology, agriculture and the food industry to increase or decrease biomass. Importantly, our research program provides a multidisciplinary, inclusive and collaborative environment for the training of the next generation of young scientists. By providing deeper insights into programmed cell, and by creating training opportunities for young researchers, our research program will contribute to a dynamic Canadian knowledge-based economy.