Validation and characterization of the caspase-6 interactome

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The role of caspase-6 in programmed cell death pathways Apoptosis, the process of a genetically programmed form of cell death that utilizes certain proteins called caspases, leads to the removal or elimination of a cell without damaging other cells in the vicinity. Once this program is triggered in the cell it causes the cell to shrink, the chromosomes and cellular organelles to condense in an orderly way and form apoptotic bodies that are then removed by neighbouring cells. Apoptosis is used extensively during development and has broad evolutionary implications applicable to all vertebrates. In an average human adult, approximately 50 billion cells die by this process per day. Research indicates activation of caspase-6, a type of molecular scissors that cleaves certain proteins, occurs early in the programmed cell death pathway and orchestrates a highly efficient series of cascades that can ultimately culminate in death and removal of a cell. When proteins are cut, the small fragments generated can also be involved in triggering and/or amplyifing the death of the cell. Despite the wealth of evidence demonstrating a critical, early role for caspase-6 in apoptosis, currently it is unclear how caspase-6 is regulated and how its activation leads to the death of the cell. Caspase-6 is highly conserved evolutionarily and thefore its role in programmed cell death has potentially wide-ranging significance towards undertanding eukaryotic development in general. My research program will identify what proteins regulate caspase-6 in order to understand how it becomes activated or suppressed, and to determine what particular proteins it cleaves. Exploring the biology of caspase-6 and other caspases in apoptotic cellular models will provide valuable new insights into the fundamental biological mechanisms underlying apoptosis/cell death as well as provide a more thorough understanding of the critical factors that influence regulation of the programmed cell death pathway.