Research Location: University of British Columbia - Point Grey

Many microorganisms reside in our bodies as part of normal living. For example, bacteria in the gastrointestinal system outnumber our own cells and form a stable connection with the body that persists for life. These resident bacteria are needed for parts of the digestive tract to develop and function properly. In addition, beneficial bacteria attach to the walls of the intestinal tract, preventing harmful bacteria from occupying these surfaces, and protect us from infectious diseases as a result. A lot of research has focused on disease-causing bacteria like E. coli and Salmonella, which are among the leading causes of gastrointestinal illness and death worldwide. Yet little is known about the role of beneficial bacteria in battling these microbes, which is the focus of Inna Sekirov’s research. She is examining what role resident bacteria play during the response of the intestinal immune system to infection and how these bacteria respond to antibiotics used to treat gastrointestinal illnesses. Findings from her research will help to establish whether drugs are likely to have a positive or adverse impact on a patient’s beneficial bacteria, and could also help inform new therapies or dietary regimes that complement or strengthen the ability of these bacteria to help the body fight infection.

Many diseases, including cancers and autoimmune disorders, arise from malfunctions of complex cellular processes. These processes regulate such things as the cell’s ability to grow, change cell type, and even die. Complex biomolecular networks, consisting of interacting genes and proteins, create the sophisticated information processing circuits within cells that control these biomolecular events. Inherited genetic defects, genetic mutations and some environmental cues can alter these networks to create abnormal cellular functioning leading to disease. Medicines treat and cure disease by controlling malfunctioning biomolecular networks. This requires a deep understanding of how cellular networks function and why malfunctioning networks fail. James Taylor’s research focuses on cellular signaling, the mechanism for processing external information that is the basis for a cell’s ability to sense the environment and communicate with other cells. He is studying how information signals flow through, and are processed by, signaling networks. The research is being conducted with baker’s yeast, a single cell organism that is commonly used for research involving fundamental cellular processes. Using computational, engineering and advanced experimental methods, Taylor is exploring how these networks create normal cell functionality and how changes in these networks lead to disease. By contributing to our knowledge of cellular signaling in yeast cells, this research will shed light on malfunctions of cellular processes in humans.

Resistance to insulin — the hormone that converts sugar into energy — leads to diabetes and high blood pressure (hypertension). Chronic hypertension can lead to cardiovascular complications like heart disease and stroke — two leading causes of death. This is a cause for concern since two million Canadians have diabetes, and this number is expected to rise to three million by the end of the decade. Consuming a diet high in fructose, a sugar used to sweeten soft drinks and other foods, causes insulin resistance and increases blood pressure. Harish Vasudevan has found that differences in gender and sex hormones play a role in the development of high blood pressure. For example, pre-menopausal women are less likely to develop hypertension than men or post-menopausal women. The female sex hormone, estrogen, protects these women against developing insulin resistance and high blood pressure. But the male sex hormone, testosterone, is required for blood pressure to elevate following insulin resistance. Fructose also disturbs the normal relaxation in blood vessels, but requires testosterone to do so. Vasudevan is examining how changes in the blood vessels depend on testosterone and estrogen. This research will further clarify the role of sex hormones in the development of insulin resistance and hypertension, which should, in turn, lead to new treatments for these chronic diseases.

DNA damage repair pathways prevent cancer by recognizing and repairing DNA damage. If DNA damage is not constantly and consistently repaired in this way, it can lead to mutations in the DNA, which accumulate over time. Without normal DNA repair pathways in action, cancer will eventually develop. Jillian Youds’ research focuses on the DNA repair pathway involved in the hereditary cancer susceptibility syndrome Fanconi anemia. Patients with Fanconi anemia have unstable chromosomes and commonly develop cancer at a young age. It is thought that these patients are unable to repair cross-links in their DNA, which can prevent essential cell processes from occurring. As these DNA repair pathways are common to many organisms, Youds is using the nematode C. elegans to conduct her studies. Using molecular biology, genetic and biochemistry techniques, Youds will study how DNA cross-links are repaired by the cell under normal circumstances. This research is relevant to patients with Fanconi anemia, and it will contribute to the development of the best possible chemotherapeutics to optimize cancer treatments. Since the loss of functional repair pathways is a contributing cause of cancer and also a means to target cancer cells for elimination during treatment, an understanding of how the DNA cross-link repair pathway works will bring us closer to the ultimate goals of prevention and successful treatment of cancer.