Characterization of oligodendrocyte abnormalities in schizophrenia

Schizophrenia is a severe psychiatric illness affecting approximately one per cent of Canadians. While the causes are not yet fully understood, it is thought that the symptoms of this disorder may arise from abnormalities in nerve fibre connections between different brain regions. Mounting evidence suggests that a contributing factor may be abnormalities in myelin, the fatty insulating substance that surrounds nerve fibres and speeds up the transmission of nerve impulses. Studies have shown reduced density of oligodendrocytes, the brain cells that produce myelin, and altered expression of several proteins found specifically in myelin—suggesting a possible source for impaired transmission of nerve impulses between brain regions. Through a series of investigations Dr. Clare Beasley is examining the role of oligodendrocytes in schizophrenia. She will characterize oligodendrocyte alterations in the brain in schizophrenia and examine their relationship with myelin proteins and lipids. By better understanding the connection between abnormalities in these myelin-producing cells and the symptoms of schizophrenia, she hopes to shed light on the cause of this devastating disorder.

Psychosocial determinants of adolescent health behaviour

There are numerous segments of the Canadian population who experience a disproportionate burden of ill health. A key issue in addressing this disparity is the early identification of those groups of people who are vulnerable to poor health outcomes over the course of their lifespan. Identification of these groups, and the factors leading to this vulnerability, is a priority for researchers. One area of interest is in identifying the early childhood determinants of health behaviours, such as a child’s health, stress in the family, economic conditions or neighbourhood safety. Dr. Stefania Maggi studies the extent to which early influences can predict which children will follow trajectories of health vulnerability throughout the lifespan. Her research uses a combination of administrative databases, national surveys, and longitudinal data collection to follow up on the same individuals over a number of years, spanning developmental phases from early childhood to adolescence and young adulthood. By identifying what factors in childhood increase the likelihood of unhealthy behaviours and/or poor educational outcomes during adolescence her research will inform early prevention efforts aimed at the social determinants of health.

Collaborative Research Team for the Study of Bipolar Disorder (CREST.BD)

This award funds the development of a multidisciplinary research team focused on examining and developing a knowledge base on the role of psychosocial factors in bipolar disorder. The goals include: identifying research priorities within the field of psychosocial issues in bipolar disorder; ensuring the team has the skills and expertise to address these priorities; identifying and establishing partnerships with existing organizations; developing research plans and a patient-centered research agenda; and identifying opportunities for sharing and leveraging resources.

Physical Activity, Local Joint Factors and Osteoarthritis

Osteoarthritis is a leading cause of disability in Canada. This type of arthritis causes deterioration in the joints, leading to swelling, pain and stiffness. It often results in lost work time and places limits on an individual’s normal function and recreational activity. Both the increasing prevalence of osteoarthritis in the province’s aging population, and the lengthy surgical wait times for replacing osteoarthritic joints are high profile health care issues in British Columbia. Physical activity can offer almost universal improvements in health, which includes decreasing the risk of heart disease, stroke, high blood pressure and cancer. Health Canada recommends all adults participate in at least 30 minutes of moderate-intensity exercise most days. But some types or too much physical activity, such as competitive sports or heavy physical work, can cause excessive wear and tear in the joints, increasing the risk of osteoarthritis. In addition, some people may be more vulnerable to the type or amount of physical activity because of the way their legs are aligned (e.g. bow-legged) and/or because of increased flexibility (hypermobility). Chuck Ratzlaff is comparing data on lifetime physical activity and these joint factors in people with knee and hip osteoarthritis to those who don’t have the condition, as part of a national arthritis study. The results can be used to recommend appropriate amounts and types of physical activities that may decrease the risk of osteoarthritis of the hip and knee.

Characterization of the function of the nuclear matrix protein Lamin A in the organization of telomeres and chromosomes to determine the role in the pathology of Hutchinson-Gilford Progeria Syndrome

Hutchison-Gilford progeria syndrome (HGPS) is a rare, fatal disease that affects children and causes accelerated aging. Symptoms include dwarfism, loss of body fat and hair, aged-looking skin, stiff joints and hip dislocation. Children with this disease usually die of a heart attack or stroke at an average age of 13. HGPS is caused by a mutation in the LMNA gene which encodes a protein called Lamin A. The mutation causes instability in the cell nucleus, which is believed to lead to the premature aging in HGPS. Michelle Decker is looking for differences in the way normal and mutant versions of the Lamin A protein interact with chromosomes in the cell nucleus. Research has shown that cells from patients with HGPS have shorter than usual chromosome ends (called telomeres) than are usually found in cells of other children. Telomeres normally protect chromosomes from degradation and instability. By improving the understanding of the role that Lamin A and telomeres have in Hutchison-Gilford progeria syndrome, Michelle’s research may contribute to new understandings and therapies for the disease.

Femoroacetabular impingement as a predictor for Osteoarthritis of the hip

Osteoarthritis (OA) is a debilitating disease characterized by the degeneration of cartilage. OA is a common disease among the elderly, affecting more than three-quarters of people over the age of 75. Research has suggested a link between the development of OA and femoracetabular impingement syndrome (FIS), a disease of the hip. In FIS, the femur makes contact with the acetabulum (the cup-like recess in the pelvis that acts as the socket in the joint), causing pain. This is most evident during periods of extreme range of motion and often occurs due a structural abnormality of either the femoral head or the acetabulum. Early detection of FIS has the potential to allow doctors to alleviate or arrest the onset of osteoarthritis. However, radiographs, which are the current standard of diagnosis, have limitations. Joshua Levitz’s research seeks to develop a better way to diagnose FIS. His study involves creating computerized, 3-D bony models of hips from MR images, to study hip alignment in both subjects diagnosed with FIS and healthy control subjects, and determine the significant factors characterizing FIS. By developing a more sensitive gold standard for diagnosing FIS, this research may provide a method for early prediction of OA.

Accelerated telomere shortening in women with breast cancer: The buffering effect of social support against physiological stress markers

Psychological stress has been frequently implicated in disease development and progression, but the determinants of this relationship remain unclear. A recent finding has demonstrated that chronic and perceived stress affects health by influencing the rate of cellular aging. The literature also shows that social support buffers against stress. Jillian Satin is exploring the relationship among stress, social support and cellular aging in women who have been diagnosed with breast cancer. While chronological age is usually used as a predictor of age-related disease, cellular aging may be a more accurate predictor of onset and a potential route of disease prevention. Jillian’s research is examining whether social support modulates the relationship between objective stressful life events and cellular aging. Since social support has been shown to decrease perceived stress, Jillian’s hypothesis is that social support decreases the accelerated rate of cellular aging. If this hypothesis is correct, it would suggest that social support interventions should be made available to those at risk and should be integrated into the health care that women with cancer receive. Although this study focuses on breast cancer, the findings could prompt further exploration into treatment of cancer and age-related diseases.

Ex vivo Engineering of Gut K-cells to Produce Insulin

Diabetes is a leading cause of death in Canada, affecting more than two million Canadians. Type 1 diabetes occurs when the pancreas fails to produce insulin, a hormone that is vital to transforming the sugars ingested in a meal to useable forms of energy. As a result, diabetic patients often depend on multiple daily injections of insulin to survive, but these injections do not prevent a series of long-term complications such as increased risk of heart disease, kidney disease and blindness. Type 1 diabetics can be treated by transplantation of islets—cell clusters from the pancreas containing insulin-producing cells—from non-diabetic donors. However, this option is severely limited by a shortage of donor islets. Therefore, there is interest in generating other cells that can also produce insulin. To be effective and safe, such cells must be capable of producing insulin in an amount that matches the quantity of sugar ingested. Like the insulin-producing islet cells, there are cells in the gut that are activated after a meal. These cells do not produce insulin, but another protein called glucose-dependent insulinotropic polypeptide (GIP). Recently, scientists were able to genetically modify these gut cells to produce insulin in addition to GIP. Building on this discovery, Irene Yu is working to develop methods to isolate and purify these cells and to determine how long these genetically modified cells can survive after transplantation. She is also testing whether these cells can effectively maintain normal blood glucose levels. If so, there will be an alternative to islets that can be used for transplantation, providing more type 1 diabetes patients with a longer-lasting treatment option.

The temporal regulation of neurogenesis during olfactory system development

Olfactory receptor neurons (ORNs) are the cells responsible for translating the odours in our external environment into the code that represents these smells in our brains. ORNs sense odours using receptors on their surface. These receptors bind the odour molecule by initiating a signalling process that results in information being transmitted to the appropriate part of the brain. Each ORN expresses only one type of receptor, and only a few out of thousands of other ORNs may express that receptor. This indicates that although all ORNs perform a similar function – sensing odours – each cell is unique. Since these cells are constantly exposed to the harsh external environment, they typically have a short life span. As a result, they are constantly replaced by new ORNS that are generated throughout life from undifferentiated cells. Thus, the olfactory system is the ideal model for understanding how an undifferentiated cell becomes a uniquely specialized neuron. Matt Larouche is seeking to define the time and place a particular ORN is produced since understanding these aspects may help explain what conditions are necessary for producing such a cell. This research will provide insight into how unique neurons are generated in the brain, and how to build specialized types of cells that can replace neurons lost due to injury. In the future, this information could be valuable for designing treatments for ailments that affect the nervous system, including strokes, paralysis and neurodegenerative diseases such as Multiple Sclerosis, Alzheimer’s or Parkinson’s diseases.

Investigation of the role Cnk2p plays in ciliary length control

Eukaryotic cilia are membrane-bound organelles in cells known for their function to propel cells (such as sperm cells), or move fluid over a cellular surface (such as respiratory epithelial cells in the lungs). More recently, researchers have looked more closely at immotile (unmoving) primary cilia which are found on almost all terminally differentiated mammalian cells (mature cells that no longer grow). Previously believed to have no function, immotile primary cilia have now been shown to have significant signalling roles and are gaining recognition as sensory organelles. A series of recent discoveries has pointed to the idea that the cilia found in tubular epithelial cells of the kidneys are required for maintaining the differentiation of kidney tubules, and that the loss of this function results in Polycystic Kidney Disease, a common human genetic disease also found in other species. Focusing on one member of a family of proteins known as the NIMA-related kinases, Brian Bradley is studying the connections between cilia, the processes by which they are assembled, and cell division. He hopes his work can lead to a better understanding of the role of cilia in human health and disease.