Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the loss of motor neurons (specialized nerve cells) in the spinal cord, brain, and descending motor tracts. ALS leads to muscle weakness and paralysis, and is often fatal. Numerous biochemical processes have been linked to the progression of ALS, including increased levels of protein modification (phosphate units). Xiaoyang Shan is researching the role of modified sugar units, known as O-GlcNAc, in maintaining the proper functioning of neurofilaments (structural proteins) that give neurons support and shape but become damaged in ALS patients. He is also investigating the role of O-GlcNAc in maintaining healthy motor function. The findings could help increase understanding of the causes of ALS, and contribute to development of a potential treatment to slow or halt the progression of the disease.
Program: Trainee
Characterizing British Columbia’s Rural and Northern Home Support Workforce: A Mixed Methods Investigation of Workers and Their Working Lives
BC’s home support system makes an important contribution to the health and well being of the province’s most vulnerable seniors. In 2004/05, home support services were provided to more than 30,000 British Columbians. Most home support users are single senior women over the age of 75, living below the poverty line. Home support consists of personal care services (e.g., bathing, dressing, feeding) as well as basic medical care (e.g., giving medication, keeping wounds clean) provided in people's homes by trained Community Health Workers. Zena Sharman is examining the characteristics and working lives of home support workers in rural and remote BC communities, within the Vancouver Island health authority. She is also investigating factors that contribute to the recruitment and retention of Community Health Workers in rural and remote BC communities. Sharman hopes her research will help improve health services delivery in these communities, particularly in the context of the aging population and related increases in demand for home support services. She also hopes her findings can improve methods of attracting and keeping Community Health Workers.
Systems biology analysis of dynamic cellular pathways
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.
Testosterone-Dependent Regulation of Arachidonic Acid Metabolism Influences the Development of Hypertension Following Insulin Resistance
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.
Volume and Shape of the Caudate Nucleus and Putamen as Biomarkers for Parkinson's Disease Progression
Parkinson’s disease is a degenerative disorder of the central nervous system. Symptoms include shaking, muscle stiffness, speech problems, memory loss and vision problems. The disease involves the inactivation of dopamine-producing cells in a part of the brain called the substantia nigra. There is no definitive test to diagnose Parkinson’s disease, making it difficult to diagnose in its early stages. By the time a patient is diagnosed, up to 80 per cent of the dopamine-producing cells may have already stopped working. There is therefore a need for a more reliable test for diagnosis of Parkinson’s disease. There is reason to believe that Parkinson’s disease can be detected by measuring the size and shape of two anatomic structures within the brain that are both connected to the substantia nigra: the caudate nuclei and the putamen. When the cells in the substantia nigra become inactive, less dopamine is sent to the caudate nuclei and putamen. Aaron Ward is studying whether a decrease in dopamine results in changes to the size or shape of the caudate nuclei or putamen. Using magnetic resonance imaging, Ward is computing a 3-D representation for each patient’s caudate nuclei and putamen. The ultimate goal is to discover aspects of the shape of these structures that could serve as indicators of Parkinson’s disease. This would allow earlier and more reliable diagnosis, and facilitate the tracking of patient response to therapy.
How the eating disorder therapist's personal experience of an eating disorder influences the therapeutic relationship with clients who have eating disorders: A grounded theory
The demand for eating disorders treatment in BC typically exceeds what is available in existing specialty programs. This service gap is often filled by community psychotherapists. Research indicates that eating disorders among eating disorder treatment professionals far exceeds prevalence rates in the general public. This suggests that there are likely to be therapists working in the field of eating disorders treatment who have recovered from, or who many currently struggle with, an eating disorder. Recovered/recovering eating disorder therapists are ethically obliged to evaluate how their personal experience may influence the therapeutic relationship with the eating disordered patient in helpful or harmful ways. Meris Williams’ research aims to enlarge our understanding of the recovered/recovering eating disorder therapist, especially how the personal history of an eating disorder influences the therapeutic relationship with eating disordered patients. She will conduct extensive interviews with 20 psychotherapists who provide services to patients with an eating disorder, and who themselves have received a diagnosis of an eating disorder. The study’s results can enhance the effectiveness of recovered/recovering eating disorder therapists by helping them assess their readiness to work with eating disordered patients. It can also help ensure that therapists’ personal experience is influencing the therapeutic relationship in a manner that benefits patients. The results could also be used to inform the education, training, and supervision of eating disorder therapists-in-training in BC. Ultimately, this research will help people seeking treatment for an eating disorder.
Improving public health through active transportation: Understanding the influence of urban infrastructure on decisions to travel by bicycle
Cycling offers great benefits as an urban transportation option in terms of public health. It’s free of air and noise pollution, and it incorporates physical activity into people’s daily routines, therefore contributing to increases in fitness, decreases in obesity, and potential declines in heart disease, cancer and diabetes. Cycling rates in Canadian cities are very low compared to those in European centres. Despite the room for growth, Canadian municipalities are struggling to accomplish even modest changes in cycling rates. Some cities have sponsored research to understand how to encourage their residents to cycle more, but none have investigated how neighbourhood characteristics and transportation networks are related to cycling rates. Meghan Winters is researching which characteristics influence cycling rates in MetroVancouver. Information about factors such as population density, hills, distances to shops and workplaces, street types and bike routes will be linked to information from more than 2,000 Vancouver area residents about whether they drive, cycle, walk or use transit for their most common weekly trips. She will measure the effect of neighbourhood characteristics and transportation networks on the likelihood of a trip being made by bicycle. By providing evidence on how to build neighbourhoods that are favourable for active transportation, this study will help make the healthy transportation choice an easier choice, thus improving the fitness and health status of the community.
The role of the DOG-1 helicase in repair of DNA interstrand cross-links in the model organism Caenorhabditis elegans
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.
Signaling Pathways Underlying Spreading Depression and Ischemic Depolarization
The visual aura some people experience with migraine headaches is caused by “spreading depression,” a wave that begins in the outer portion of the brain and spreads throughout the gray matter. During the wave, nerve cell activity lessens and brain tissue swells. A similar wave, called ischemic depolarization (ID), occurs during a stroke. Ischemic strokes cause the sudden death of brain cells when blood flow to the brain is blocked. Although spreading depression was first reported more than 60 years ago, researchers are still unclear about how the wave is generated. Ning Zhou is using a new imaging technique, called two-photon laser scanning microscopy, to examine detailed changes in individual cells when brain tissue suffers from spreading depression or ischemia (insufficient blood supply). Although these two events are similar, brain cells do not die during the wave of spreading depression. Zhou will examine the differences to discover why nerve cells undergo unusual swelling during spreading depression, and how this contributes to cell death during stroke. This research could provide insight into how to prevent tissue damage induced by strokes.
The affects of Mgat5 modified glycoproteins and galectin-3 on the expression, phosphorylation and function of connexins
Cells in the human body are not isolated entities; in fact, they engage in a considerable amount of ‘cross talk’ with other nearby cells. In the most direct form of communication, protein channels pass through the membranes around neighboring cell, allowing small molecules to pass back and forth. These channels, called “gap junctions”, are made up of proteins called “connexins.” Of interest to researchers is the discovery that production of connexins is reduced in aggressive cancers compared to the surrounding tissue. It is due to observations such as this which has led scientists to believe that connexins do more than just form “tunnels” between cells. Stephen Bond is examining the link between connexin 43, the most common form of connexin, and an enzyme called Mgat5. Too much Mgat5 encourages tumour growth, and “knocking out” this enzyme (making it inoperative) increases the amount of connexin 43 protein made. Bond wants to determine whether an increase in Mgat5 increases tumour growth by decreasing connexin 43, and if so, determine how this occurs. This research could identify yet another way in which cells become cancerous, thus increasing our understanding of this class of disease, and hopefully lead to more effective treatments for cancer patients in the future.