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Life and Death Decisions
The Barker lab studies biochemical signals, which determine whether neurons survive and grow or, instead commit suicide through a process called apoptosis. Neurons make these life-and-death decisions in response to a family of molecules called neurotrophins, which are secreted into the environment surrounding the cells. Neurotrophins bind to and activate specialized proteins called receptors, which are located on the surface of the cells (Fig. 1). The interaction between a neurotrophin and its receptor is like a key fitting into a lock: the receptor contains a binding site which specifically accommodates the neurotrophin. Once activated by the binding of a neurotrophin molecule, the receptor initiates a cascade of biochemical events inside the cell. Depending on the specific circumstances - e.g. the type of neurotrophin, the type of receptor or the specific properties of the cell - these biochemical signals may cause the nerve cell to thrive or to kill itself by apoptosis. We are especially interested in a type of neurotrophin receptor called p75 NTR, which is important for normal apoptosis and which has also been implicated in Alzheimer's disease, amyotropic lateral sclerosis (ALS) and the irreversible damage that occurs after nerve injury.
It may seem surprising that nature would evolve a process by which cells would initiate their own deaths. However, this process of apoptosis has a number of crucially important biological functions. For example, during the early stages of nervous system development, the brain actually makes more neurons than it needs. The excess neurons - those that fail to make the proper connections with other neurons - are selectively pruned through apoptosis. Indeed, abnormalities of apoptosis may be involved in disorders of brain development such as autism. Apoptosis also has an important role in the body's defence against cancer. Various cell mechanisms detect damaged or otherwise abnormal cells and destroy them through apoptosis before they begin uncontrolled cell division to form a tumour.
Although apoptosis is crucial for normal body homeostasis, such as eliminating potentially cancerous cells and determining the appropriate number of cells in the brain and other organs, this process may also contribute to some of the most serious disorders of the brain and nervous system. Alzheimer's disease, ALS and the events following stroke all share in common the progressive loss of neurons. By gaining a better understanding of the processes that initiate and execute cell death we may be able to intervene and thus arrest the neuronal death associated with these devastating conditions.
Phil Barker, Professor in the Departments of Neurology and Neurosurgery, and Anatomy and Cell Biology, is a molecular biologist and biochemist. He received his PhD from the University of Alberta and completed his post-doctoral training at Stanford University. Phil co- founded a successful biotech company and served as Director of the Neuro’s $15 million Centre of Excellence in Commercialization and Research award.
