Research Pillar: Biomedical

Campylobacter jejuni (Cj) is the leading cause of bacterial food poisoning in the world. Each year about 300,000 Canadians are infected by these highly invasive bacteria through ingestion of undercooked meats or dairy products. An acute infection causes diarrhea, fever, vomiting, and, occasionally, death. Cj infection may also lead to Guillain-Barré Syndrome, an autoimmune disease that causes weakness or tingling in the legs and arms. In some cases, symptoms can become so severe that the patient is almost totally paralyzed. Most people recover, although some continue to have some degree of weakness. Ann Lin is researching how Cj bacteria cause disease in the gastrointestinal tract. Cj is predominantly found in the first and last sections of the small intestine and the colon. The bacteria penetrate layers of cells in the intestine and infect underlying tissues. Lin is examining whether this process disrupts the intercellular junctions that provide integrity for host epithelial cells. Disrupting this barrier is believed to contribute to diarrhea, but the molecular process is not well understood. Lin will determine whether Cj causes gastrointestinal disease by damaging the barrier. Ultimately, her findings could lead to the development of new methods of preventing Cj infection.

Chromosomes, which are a compacted form of DNA, must be accurately duplicated and separated into two new daughter cells during each cell cycle. Genetic instability arises when chromosomes are separated improperly. This error is the source of many diseases, such as cancer and Down’s syndrome. Accurate chromosome separation relies on machinery assembled on each chromosome called the kinetochore. The regulation of the kinteochore is essential for cellular fitness and prevention of genetic instability. Understanding the mechanism by which the kinetochore is regulated will lead to a better view of cellular division and will provide insight into the treatment of diseases such as cancer. Because chromosome separation is a fundamental cellular process in all types of cells, Jennifer McQueen is using budding yeast as a model to study chromosome segregation. She is using many genetic and biochemical tools to examine the involvement of the Mck1 kinase in chromosome separation. Her project aims to discover a new role for the Mck1 kinase in kinetochore function and to produce a new model of kinteochore regulation that is applicable to human health.

Normal brain activity involves the controlled transmission of electrical impulses across networks of neurons (nerve cells). Occasionally, undesired electrical activity occurs within cellular networks and a response is necessary to suppress this outburst. Kirk Mulatz is investigating a negative feedback mechanism that allows neurons to inhibit this atypical electrical activity. He is focusing on the role of T-type calcium ion channels in generating this aberrant electrical activity, and exploring the effectiveness of inhibiting characteristics of the channels to inhibit the activity. Investigations into negative feedback mechanisms both increase understanding of normal brain activity and how cells respond to abnormal activity. A number of neuronal disorders such as epilepsies, mood disorders and chronic pain are associated with atypical brain activity, and the feedback mechanism that Mulatz is researching may contribute to restoring normal activity across cellular networks.

Certain strains of Escherichia coli (E. coli) bacteria can be harmful and cause disease; other strains are harmless and live harmoniously with their host. In fact, harmless strains of E. coli colonize the human intestine shortly after birth and survive there. In contrast, the disease-causing strains produce a wide variety of infections, including meningitis, urinary tract infections and intestinal infections. Enterohaemorrhagic E. coli (EHEC) colonizes the small intestine and induces severe bloody diarrhea. It is a significant cause of illness and death worldwide. EHEC attaches to the surface of cells lining the intestinal walls. These epithelial cells have microvilli, which are small finger-like projections that increase the surface area available to absorb water and nutrients. EHEC causes flattening of microvilli, which enables the bacteria to bind tightly to the intestinal cells and inject effector proteins into the interior of the host cell where they disrupt normal host cell processes and cause disease. Seven novel EHEC effector proteins have been identified and the mechanisms of their function are unknown. In her research, Stephanie Shames is working to identify host proteins in epithelial cells that are targeted by the seven novel EHEC effector proteins and to describe the interaction that occurs between these host and bacterial proteins. This research may provide important insights into how EHEC causes diarrhea which, in turn, could lead to the development of better methods of treatment and prevention, with world-wide benefits.

Diabetes is a rapidly growing worldwide epidemic. It’s estimated that by 2030, more than 366 million people will have the disease, many of whom will acquire additional conditions such as neurological dysfunction, kidney failure and cardiovascular disease. Between 90 and 95 per cent of diabetics have type II diabetes mellitus. This results in hyperglycemia and hyperlipidemia (high glucose and fat in the blood), which causes cell death in the beta cells that produce insulin. This further reduces insulin output, accelerating other conditions associated with diabetes. However, by increasing insulin secretion and promoting survival of beta cells, it should be possible to reduce or prevent the conditions associated with type II diabetes. Glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived peptide hormone whose stimulatory actions enhance insulin secretion and inhibit beta cell death. However, the mechanisms by which GIP protects beta cells are unknown. Scott Widenmaier is studying the possibility that GIP prevents beta cell death by relieving the stress placed on the mitochondria, the cell’s energy producing machine. It is expected that this protective mechanism of GIP will provide key information regarding the effects of chronically-high glucose and lipids on beta cells in type II diabetics. This could lead to a novel class of therapeutics to prevent beta cell death, contributing to better health outcomes for type II diabetics.