Research Pillar: Biomedical

Salmonella enterica serovar Typhimurium is a bacterium that causes gastroenteritis, a type of food poisoning characterized by abdominal pain, fever, vomiting, and diarrhoea. Most Salmonella infections arise from oral ingestion of tainted food or water and are a significant cause of disease and death in animals and humans worldwide. Dr. Brian Coombes is studying the molecular mechanisms by which Salmonella use virulence factors to modify their host environment. Once injected into mammalian host cells, these virulence factors rearrange and reprogram the cells so that Salmonella can replicate and evade the body’s immune system. Learning more about how bacteria use specific virulence factors to manipulate their environment during infection may lead to the design of new therapeutic strategies to treat or block the disease process.

Escherichia coli (E. coli) bacteria cause numerous diseases including meningitis, urinary tract infections and diarrhea. Worldwide, enteropathogenic E. coli (EPEC) is one of the leading causes of diarrhea in children and is an endemic health threat in the developing world, causing the death of several hundred thousand people each year. Isolated outbreaks of enterohaemorrhagic E. coli (EHEC) also occur in developed countries, often transmitted in contaminated hamburgers and water supplies, and can cause diarrhea and fatal kidney disease. After binding to the cells that line the intestine, E. coli injects several proteins that lead to diarrhea and disease. Dr. Philip Hardwidge aims to identify these proteins and determine their structure and function. He is also examining how intestinal cells respond to E. coli at the level of gene expression, using an advanced technique to analyze several thousand genes at a time. This research could guide the design of future vaccines and antibiotics to prevent and treat E. coli.

Close to 250,000 Canadians over the age of 65 have Alzheimer’s disease. The leading cause of dementia, Alzheimer’s is a degenerative disease characterized by loss of memory, judgement and reasoning, and changes in mood and behaviour. There is no known cause or cure. Within the brain, cells shrink or disappear and are replaced by dense spots, or plaques, which contain a protein called beta amyloid. Recent studies show chronic inflammation in the brain cells plays an important role in the development of Alzheimer Disease. Microglia — the smallest cells surrounding neurons — seem to contribute to this process, and the beta amyloid protein interacts with these cells. Dr. Aline Stephan is studying how amyloid deposits inside the brain induce neural changes to affect synaptic processes and memory function. Her research will help explain how inflammation exacerbates memory deficits, and may lead to new therapies to treat the disease.

Dr. Ross Waller’s earlier research into the malaria parasite has contributed important information leading to a new array of drugs to treat the disease. Now he is studying microsporidia, a group of intracellular parasites that infect humans and animals. In particular, microsporidia infect immune-compromised individuals, causing encephalitis (inflammation of the brain) and gastroenteritis (inflammation of the stomach and intestines). The parasites have a remarkable method for invading host cells. This small, simple spore releases a harpoon-like tube that pierces the host cell. The parasite contents are then injected into the host through this tube, establishing the infection. Ross is identifying specific genes and proteins involved in the infection process, using genome sequences that have identified all the genes in two microsporidia. He is looking at the way proteins are prepared prior to and during the initial stages of infection. The results may provide new ways to combat these organisms.