Program: Trainee

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.

Tuberculosis (TB) is a contagious illness of the respiratory system that is spread through coughing and sneezing. This chronic infectious disease is caused by a bacterial microorganism, Mycobacterium tuberculosis. This bacterium infects one in three people worldwide and claims the lives of two to three million people each year. The incidence of TB is on the rise due to the emergence of multi-drug resistant strains and escalating numbers of HIV-linked deaths. These alarming trends have led the World Health Organization to declare tuberculosis a global health emergency. Pathogenicity of this bacterium is due in part to its unusual ability to survive for long periods of time and to replicate in human immune cells. The mechanisms behind this persistence are poorly understood which is why Katherine Yam is investigating a number of genes essential to pathogenesis of M. tuberculosis. Studies recently revealed that some of these genes are involved in degradation of cholesterol — a source of energy for the bacterium during infection. Yam is studying two of these cholesterol-degrading enzymes, HsaC and HsaD, which help the bacterium survive in the human body. By designing inhibitors for these enzymes, the cholesterol-degrading pathway of M. tuberculosis can be blocked, which will reduce the bacterium’s ability to cause disease. These enzymes are excellent new targets for TB drug treatments as they are not targets of current drugs and thus will circumvent the problem of drug resistance in TB.

Salmonella bacteria cause severe intestinal infection and diarrhea in humans. Millions of cases of Salmonella infection occur every year, predominantly in developing countries. However, salmonellosis is still a persistent problem in developed nations; young children, the elderly, and people with compromised immune systems are the most likely to have severe infections. Salmonella bacteria infect human cells and somehow manage to avoid activating the immune system from attacking them, allowing the bacteria to replicate. How these bacteria evade the host immune system response is poorly understood. Salmonella bacteria secrete proteins, called effectors, directly into the host cell through a needle-like channel. Dr. Amit Bhavsar is researching how these effectors bind to other host proteins in human cells; how the host proteins’ ability to function is affected; and how this enables Salmonella to evade the immune system. This research will result in a better understanding of how Salmonella bacteria evade the host immune system. It could also lead to new ways of restoring the immune system to fight infection, providing an alternative to conventional antibiotics, which have become less effective in the face of antibiotic resistance.

Stroke is the leading cause of adult disability, often rendering its victims with profound impairments in sensory, motor or cognitive function. Fortunately, many individuals experience some partial form of recovery over the ensuing weeks, months and years after stroke. This recovery of function is thought to be dependent on how well surviving brain cells (called neurons) and their connections adapt and form new circuits. However, the nature by which these neurons change in a living organism and the factors that regulate these changes, has not been determined. Craig Brown’s research is aimed at determining how the parts of the neuron that receive information (dendrites) and those that transmit information to other cells (axons) reorganize after stroke. Given that neurons are critically dependent on sufficient levels of blood flow to survive and flourish after stroke, he is also examining structural changes in brain blood vessels and their delivery of blood to vulnerable regions of the brain. He will then examine how therapeutic interventions, such as movement-induced therapies or sensory/electrical stimulation, influence brain reorganization. A better understanding of how the brain adapts to injury and the factors that regulate these process will pave the way for future therapies to optimize recovery of function after stroke.