Research Location: University of British Columbia

Canada has a growing diabetes epidemic, which costs the Canadian health care system an estimated $13 billion annually. More than two million Canadians have the disease, and by 2010, the number is expected to increase to three million. Diabetes is also a major health problem worldwide. Although diabetes can be treated with insulin, a cure for this devastating disease remains elusive. All forms of diabetes are associated with the loss of functional pancreatic islet cells. However, very little is known about the underlying factors controlling how and why pancreatic islet cells die. Dr. James Johnson recently discovered important networks of molecules that control survival of islet cells. For example, one such network includes the RyR2 protein, which controls the release of calcium in the cell, and the calpain protein, which can split other proteins in response to increased calcium. Dr. Johnson is comparing the role of this survival network to other molecular networks to investigate how pancreatic islet cells die. The research could lead to better therapies for diabetes, including more successful pancreatic islet transplantation, a promising experimental treatment that depends critically on the continued survival of the donated cells. The findings could also improve understanding of other diseases where calcium is involved in cell death, such as heart failure, Alzheimer’s disease and stroke.

Parkinson’s disease is a chronic, progressive disorder that affects about 100,000 Canadians, at an annual cost of more than $2.5 billion. The disease involves loss of both brain cells and chemicals that modulate communications between brain cells – causing not only motor symptoms of tremor, stiffness, and slow movements but also cognitive and behavioural changes. Conventional drug therapy for Parkinson’s disease replaces dopamine in the brain. Although most motor deficits usually improve after therapy, more than 50 percent of patients (particularly those in the later stages of the disease) may develop difficult problems, such as involuntary movements, dementia and psychosis. Dr. Chong Lee is studying neural mechanisms of these complications, which are resulting from the disease itself or the chronic use of Parkinson’s drugs. Dr. Lee is also evaluating the effectiveness of neuro-protective treatment, a strategy to prolong the survival of injured cells and slow the progression of Parkinson’s disease. He ultimately aims to develop strategies to treat dementia and behavioural symptoms of the disease and to reduce or prevent treatment-induced complications in patients with Parkinson’s disease.

Cells must accurately duplicate their chromosomes (genes in the cell’s nucleus) and segregate them equally to daughter cells for proper cell growth and division. Errors in segregation results in cells with abnormal numbers of chromosomes (aneuploidy), which can lead to birth defects, Down’s syndrome and cancer. Cells have developed safeguards to ensure chromosomes are accurately segregated. A region of each chromosome called the centromere is bound by kinetochore proteins which attach to spindle microtubules, tiny fibres that pull newly separated chromosomes to each side of a dividing cell. If any mistakes occur in spindle attachment, kinetochore proteins signal the spindle checkpoint machinery, which delays segregation until the defects are corrected. Using yeast as a model, Dr. Vivien Measday is studying how kinetochore proteins attach to spindle microtubles and communicate with the checkpoint machinery. The research will improve understanding of chromosome segregation and could lead to treatments for diseases caused by abnormal numbers of chromosomes.

Degenerative diseases have an enormous economic and social impact on BC’s aging population. In the long term, identifying cells that could regenerate organs damaged by degenerative diseases could revolutionize how these conditions are managed. Care could shift from expensive, lifelong drug treatments to therapies that permanently restore organ function. Research suggests that bone marrow contains stem cells (precursor cells that have the ability to develop into cells specific to types of tissues) capable of repairing damaged tissues in adults. To efficiently use stem cells, however, the cells responsible for tissue repair must be identified from among the many cell types present in bone marrow. Dr. Fabio Rossi is identifying bone marrow cells that repair damaged muscle, exploring their characteristics and investigating how they repair damaged tissue. Findings could lead to therapies that efficiently restore organ function.