Potassium channels play an essential role in controlling the activation of neurons (nerve cells), myocytes (muscle cells) and the endocrine system. In particular, their proper function and behaviour in the heart is of the utmost importance in maintaining proper cardiac function. Acidosis (a lowering of blood pH) is caused by cardiac ischemia, or an insufficient blood supply. It has been shown that acidic pH levels alter ion channels, possibly through a structural change in the pore region. This condition is linked to cardiac abnormalities such as arrhythmias and cardiac arrest. Moninder Vaid is focusing on acidic alteration of cardiac ion channel function to determine how pH modulates ion channel structure. He using fluorescent techniques to further examine how ion channels work in mammals. Ultimately, this research will provide insight into the effects of cardiac ischemia.
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Exploring RNAi technology for the treatment of Huntington's disease
Huntington’s disease (HD) is a debilitating genetic disease affecting approximately one in 10,000 individuals. HD is the most common inherited brain disease and is caused by an abnormal protein called mutant huntingtin (muHtt). Symptoms of the disease include cognitive impairment, motor dysfunction and psychiatric disturbances that usually develop around midlife. Many treatments are under investigation in mouse models of HD to potentially cure this debilitating disease. While some pharmacological agents show promise in treating HD, most act on isolated or late-onset symptoms that fail to target the disease’s greatest underlying pathological insult, the muHtt protein itself. Laura Wagner’s research is exploring RNA interference (RNAi), a natural cellular mechanism with intriguing therapeutic potential to block production of the muHtt protein in hopes of slowing or preventing HD symptoms before they start. She is using a transgenic model of HD to test RNAi constructs and their ability to prevent muHtt expression in the brain. The model will be monitored for brain changes as well as behavioural and motor function improvements as indicators of the effectiveness of RNAi treatment. In addition to testing a novel treatment for HD, this research will contribute to continued efforts in advancing medical care from a late-stage symptomatic approach to earlier, preventative therapies such as gene-targeted treatments.
Neurexins and Neuroligins in Synapse Development
Messages are relayed through the nervous system by release of neurotransmitters from an axon of one neuron, which travel across the synaptic cleft and bind to receptors on a dendrite of the next neuron. The axon terminal, synaptic cleft and dendrite are collectively called the synapse. The formation of synapses—known as synaptogenesis—is the most central process in the development and maintenance of the nervous system. New synapses are formed during learning and memory and the maintenance of synapses can be altered in disease and drug-induced states. Katherine Walzak’s research is focusing on the process by which synapses form and change with experience. Specifically, she is exploring how neurotransmitter receptors on postsynaptic dendrites are aligned with neurotransmitter release sites on presynaptic axons, and how cell adhesion molecules influence synapse differentiation and localization. By understanding the mechanisms by which synapses forms and are maintained, this research may lead to further insights into disease that may involve the alteration of synaptogenesis, such as Alzheimer’s, schizophrenia and autism spectrum disorders.
Dynamic Risk Factors for Violence in People With Major Mental Disorders
Major mental disorders are associated with increased rates of violence, which is a primary reason for involuntary psychiatric or community treatment for individuals with mental disorders. Within psychiatric inpatient units, violence compromises the safety of hospital staff and other patients, adversely impacts staff morale, jeopardizes the therapeutic setting, and presents a risk of physical injury. In order to prevent violence, it is important to identify the factors that can provoke violent outbursts. Certain known risk factors for violence do not change during a person’s life, such as their age at a first violent incident or early childhood maladjustment. However, there are also dynamic risk factors – such as emotional distress, treatment compliance, and symptoms of psychosis – that can and do vary over time. Catherine Wilson is studying a group of psychiatric inpatients admitted for treatment of a major mental disorder. Using specialized methods, she will measure these dynamic risk factors over time, from admission to discharge. The findings of Catherine’s study will increase our theoretical understanding of violence and assist the development of treatment and management programs designed to prevent violence by psychiatric inpatients.
The development and evaluation of a novel hybrid exercise rehabilitation program for the improvement of the health-related quality of life and overall health status of persons with spinal cord injury
More than 35,000 Canadians are living with spinal cord injury (SCI), and recent research indicates that this population is at an increased risk for chronic disease, particularly cardiovascular disease. In fact, individuals with complete tetraplegia (paralysis of all four limbs) are at a markedly greater risk of death resulting from cardiovascular disease in comparison to the able-bodied population, due to factors such as obesity, inactivity, increased risk for blood clots and lower levels of “good” cholesterol (HDL). Hybrid exercise training (involving the concurrent exercise of the arms and legs) is thought to have the potential to lead to marked improvements in the overall health status of persons with SCI. However, no investigations have been performed to evaluate and define the best hybrid exercise program for the treatment and rehabilitation of persons with SCI. Shirley Wong’s research is focused on developing and evaluating a novel intervention program involving hybrid exercise training for persons with SCI. The ultimate goal of Shirley’s research is to reduce the risk for chronic disease and improve the overall health status and quality of life for persons living with SCI.
First Nations Women Leaders: Building a Bridge from Cultural Identity to Healthy Youth
In British Columbia, First Nations youth are five to 20 times more likely to die by suicide than their non-Aboriginal peers. These youth suicide rates, however, are not uniformly high across the almost 200 First Nations communities in BC. Research has found that suicide rates are lowest in those communities that have been especially successful in preserving and promoting their cultural heritage and in securing local control over key aspects of community life. More recently, it has been found that suicide rates are lower in communities where women actively participate in their local government. Robin Yates is exploring the relationship between First Nations women leaders, cultural identity, and lower suicide and injury rates of youth in BC First Nations communities. The results of her research will enhance the development and exchange of knowledge regarding factors that preserve and promote healthy youth in First Nations communities.
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 role of CD72/CD100 interactions in NK cell activation
Resistance to cancer and infectious diseases relies on complex responses in our immune system. Natural killer (NK) cells provide a first line of defence, recognizing and killing infected and tumour cells, while sparing normal cells. NK cells use an intricate system of proteins, found on their surface, to either activate or inhibit their “natural killer” activity. However, the mechanisms by which these proteins induce this action are not completely understood. Dr. Valeria Alcón is studying two cellular proteins (CD72 and CD100) that are involved in the activation of several immune cells to determine how these proteins regulate natural killer cell activity. She is also examining how NK cells interact with other immune system cells to induce immune responses. Her research could explain how to activate natural killer cells, leading to the development of more effective treatments for infectious disease and cancer.
Molecular mechanism of Prp24-mediated U4/U6 formation
Messenger RNA (mRNA) is a single-stranded molecule of ribonucleic acid found in the nucleus of cells that transmits the genetic information needed to produce proteins. This production process involves “splicing” of the mRNA, whereby non-protein coding sections are removed. The splicing process must be precise as errors can result in genetic disease. For example, mutations in BRCA1, which are implicated in some breast cancers, and mutations in SMN2, which cause spinal muscular atrophy, result in defective splicing of their messenger RNA. To minimize mistakes, the cell regulates splicing. However, many of the details of this process are unclear. Dr. Kelly Aukema is studying the molecular mechanisms involved in splicing, using fluorescence resonance energy transfer (FRET) – a cutting-edge technique for measuring interactions between two molecules. She will use FRET to investigate the structural RNA changes of the molecular machinery that carries out splicing. This knowledge should ultimately lead to a better understanding of, and more effective treatments for, splicing-related diseases.
Molecular analysis of Mycobacterium tuberculosis protein phosphatase
Tuberculosis (TB) causes about eight million new infections each year and up to three million deaths. Already one of the leading causes of death world-wide, the number of deaths from tuberculosis continues to increase as new, antibiotic resistant strains and co-infections linked to HIV emerge. A third of the world population has been exposed to Mycobacterium tuberculosis, the bacteria that cause TB. The disease is spread from one person to another, when someone with TB coughs or sneezes and people nearby breathe in the bacteria and become infected. TB most commonly affects the lungs, attacking and destroying tissue, but also can spread to other parts of the body. Despite its prevalence and long history, little is known about the survival of the pathogen in macrophages. Dr. Horacio Bach is studying how proteins secreted by TB bacteria enable them to evade the body’s immune defenses and survive to multiple inside host cells. This research should help explain the cellular mechanisms involved in causing the disease, and could lead to new therapies for controlling tuberculosis bacterial infections.