Under normal circumstances, the vagina is home to many different microorganisms. A shift in the balance of vaginal microbiota can result in infections such as bacterial vaginosis (BV), the most common cause of vaginal infection. BV and other infections are associated with early pregnancy loss, preterm labour, and an increased risk for HIV. Our primitive understanding of the complex microbial ecosystem of the genital tract greatly hampers our ability to identify and describe normal vaginal microbiota. This hinders the development and evaluation of appropriate, focused therapies for genital infections. The use of high throughput molecular methods promises to be very effective for characterizing vaginal microbiota. This award supports the development of a multidisciplinary, team of researchers, with links across Canada, to apply molecular methods for microbial species identification. Their comprehensive description and monitoring of vaginal microbiota will facilitate the development of new diagnostic technologies and therapies for infection-related problems in obstetrics and gynecology.
Year: 2008
Workplace Traumatic Exposure Team
One of the most serious effects of occupational stress is mental illness — a prominent health issue in terms of both financial and human costs. It is estimated that mental injury claims are approximately 50 per cent more costly than physical injury claims, since workers with a mental injury are typically absent from work longer than those with a physical injury. Post traumatic stress disorder (PTSD) and anxiety disorder are the most significant mental injuries originating in the workplace. The majority of workers will encounter an emotionally traumatic work event at some point in their career. Despite the negative implications for the worker and for society, workplace traumatic exposure has not yet been extensively studied in BC. This award supports the development of a team consisting of researchers at UNBC and UBC who are working to pool their individual expertise in workplace traumatic exposure. The team will develop their research around description/understanding, prevention, remediation and policy/knowledge translation.
Improving Access to Quality Cancer Care using Operations Research Methods
Radiotherapy is used for curative and palliative (symptom relief) purposes for patients with cancer, with 30 to 40% of patients receiving radiotherapy during some point in their illness. Wait times for radiotherapy have been shown to lead to poorer outcomes for those treated as part of curative treatment, and to increased suffering for those treated for palliative reasons. Wait times occur either because of equipment and/or staff shortages, or due to resources not being used in the most optimal manner. Demand for radiotherapy fluctuates over time, leading to unpredictable surges in demand that are difficult to meet in a timely fashion.
Dr. Scott Tyldesley is working to improve understand of the root causes of the fluctuation in demand for radiotherapy, and to develop approaches to predict and address demands. He, and his colleagues, are creating a detailed model of the radiotherapy system, which will allow him to simulate current cancer patient flow, and to test proposed improvements to the system. Development of the model will also allow the group to explore how the radiotherapy system can improve how it forecasts demand for services, and how it deploys its resources. These results will be tested in system-wide models and then considered for implementation at the BC Cancer Agency (BCCA). The research team is a unique collaboration between specialists in operations research from the Sauder School of Business at UBC and clinical decision-makers and administrators from BCCA. The results of Tyldesley’s research will directly affect clinical practice for patients with cancer and be transferable to other health care environments.
Bioinformatic approaches for the interpretation of cancer genomes
The rapidly developing field of genomics is providing increasingly powerful tools to investigate our genetic make-up and provide a fundamental understanding into how cells and organisms function. Previously funded by an MSFHR Scholar award, Dr. Steven Jones’ ongoing research focus is to apply genomic and bioinformatic technologies to cancer research. Next-generation DNA sequencing machines at Canada’s Michael Smith Genome Sciences Centre provide the underlying technology platform for Jones to conduct a number of studies that will expand our knowledge about the fundamental mechanisms underlying health and disease. Jones will develop a number of studies around three key themes: • Understanding the genetic changes present in human cancer cells, as compared to the normal human genome, to improve drug screening and testing methods. • Investigating the changes that occur in cells in response to drug treatments to identify ways to improve the efficacy of these drugs. • Using the mouse liver as a model, identifying active regions of the genome in order to further understand the functional elements within our genetic material and how, in concert, they are able to coordinate and maintain the activity of a tissue or organ.
The role of the CD34 family of Sialomucins in Development and Disease
Dr. Kelly McNagny studies the CD34 family of molecules: CD34, Podocalyxin, and Endoglycan. First identified solely as markers of blood stem cells and blood vessels, McNagny’s research has shown that they are also present on a variety of other cell types in the body. In particular, they are found on cells that play an important role in inflammatory diseases like asthma, allergies, arthritis, multiple sclerosis, intestinal infections and cancer.
Previously supported by MSFHR as a Scholar, McNagny’s current focus is to determine whether these molecules are important in the development or progression of inflammatory disease. Developing mice that lack each of these molecules, then testing their susceptibility to disease, has shown that mice that that lack CD34 are strikingly resistant to asthma, allergies and other lung inflammatory diseases. McNagny has also shown that these mice are more resistant to colon cancer and to bacterial infections.
Inhibiting CD34 expression may be beneficial in preventing or treating these diseases. In studies of Podocalyxin, the second member of this family, it appears that this molecule is essential for normal kidney development and for regulating normal blood pressure. McNagny has also found that this protein is ‘turned on’ in a number of high-risk cancers (those with very poor outcomes). This molecule may be a particularly good diagnostic tool for identifying those high-risk cancers. He will further clarify how these molecules work under normal and disease conditions. The research could lead to new treatments for a variety of conditions and diseases.
British Columbia Burden of Injury
Injuries are a significant public health problem in BC. Every year about 1,600 British Columbians die due to injury, 42,000 are hospitalized, and an estimated 400,000 people throughout the province sustain some sort of injury. The cumulative effect of injury on a population is known as the burden of injury. Burden of injury data help policy makers and practitioners determine the effectiveness of current services in injury prevention and injury treatment, and provide direction about new interventions that would have the greatest impact. They also help provide estimates for recovery time across different injuries. However, very little is known about the burden of injury, making this an important priority for research.
Dr. Mariana Brussoni is leading a longitudinal study in BC to quantify the impacts of injury on individuals and on the health system. Drawing on her experience working in England with international experts in injury research and prevention, Brussoni is recruiting more than 1,400 injured people of all ages across urban and rural settings in BC. They will be followed for 12 months post-injury, with the research team tracking their quality of life and recovery, use of health and social services, and time away from school or work. The goal of this research is to more fully describe the various impacts of injury in British Columbia, and to identify areas where prevention and treatment interventions could make the biggest difference.
Genomic neighborhoods and inherited disease: the case for SIOD
While completing medical training in clinical genetics, Dr. Cornelius Boerkoel was consulted on two patients with a rare disease called Schimke immuno-osseous dysplasia (SIOD). At the time, there was little known about the disease, other than that it involved kidney failure and abnormal bone growth causing short height. Dr. Boerkoel’s early research in this area highlighted several previously unknown features of this disease, including the cause of SIOD: mutations (alterations) in both copies of a gene named SMARCAL1. He has also shown that SIOD arises from abnormal activity across most genes. Working with fly and mouse models that he developed to study SIOD, Dr. Boerkoel has created a model for studying how many small alterations in gene expression can cause disease.
Since common diseases such as atherosclerosis, stroke, endocrine dysfunction, immunodeficiency, and poor growth are all features of SIOD, this research is relevant to a better understanding of various unstudied mechanisms underlying these common diseases in the general population. To continue this work, Dr. Boerkoel will complete characterization of the function of SMARCAL1 using biochemical, fruit fly and mouse studies. He will test whether hormone supplementation might be an effective treatment for SIOD. Dr. Boerkoel will also determine whether the gene expression changes observed in SIOD are a feature in other patient populations affected with diseases also found in SIOD. This research will develop a new and unique model for understanding how changes in gene expression can predispose individuals to disease.
Production of high-quality proteins in plants for screening and treatment of human lysosomal storage diseases
Lysosomes are structures that digest materials within the cell. Lysosomal storage diseases are devastating diseases caused by deficiencies of specific enzymes within the lysosomes. Mucopolysaccharidosis I (MPS I) is a progressive lysosomal storage disease that affects most organ systems. In severely affected humans, this genetic disease leads to early death because of profound disturbances to the heart, brain and other organ systems. One way to correct lysosomal enzyme deficiency is through using purified enzymes for enzyme replacement therapies (ERT). However, the current methods used to commercially produce the enzymes for ERT are prohibitively costly. Because of this, sustained financial support for ERT among affected Canadians is uncertain. Dr. Allison Kermode is exploring whether using plants as hosts to produce these human enzymes will offer a more economical way to provide ERT treatments for MPS I, as well as for Gaucher disease, another lysosomal storage disease. She will test whether plant-made human enzymes are effective as ERTs. She will also establish a plant-based system for assessing potential small molecule treatments for these diseases. Finally, in collaborative work, Kermode will test plant-made lysosomal enzymes in assays for newborn screening of lysosomal storage diseases. Some of the research will be expanded to other therapeutic proteins relevant to Type I diabetes, providing a general platform for plant production of therapeutic proteins.
Structural dynamics of hERG potassium channel gating studied using voltage clamp fluorimetry
Ion channels are cardiac membrane proteins that control the flow of ions like sodium and potassium in and out of heart cells, regulating both cardiac electrical impulses and the contractions associated with the heart beating. Voltage-gated potassium channels, such as the human ether-a-go-go related gene (hERG). are a class of ion channels that open and close – an action known as gating – in response to changes in the electrical potential across the cell’s plasma membrane. In the heart, hERG channels play a crucial role in regulating heart rate and rhythm. Reduced hERG channel function has been associated with loss of the normal heart rhythm and sudden cardiac death. The unique role played by hERG channels in the heart is a result of their unusual gating properties. However, there is limited knowledge about the molecular mechanisms of these gating processes and how they are modulated.
Dr. Tom Claydon is using a new fluorescence technique that he established as a post doctoral fellow that provides a real-time analysis of the protein motions that cause hERG channels to open and close. With a small fluorescent probe attached directly to the channel protein, Claydon’s team can directly study movements that occur within the channel as it opens and closes and measure the electrical current passing through the channel during this activity. Only a handful of researchers worldwide are currently using fluorescence experiments to study ion channel gating. These experiments will provide a comprehensive and unparalleled view of hERG channel function and how it is modulated in health and disease. An understanding of these processes will lay the foundation for new therapies for cardiovascular disease.
Improving Sensitivity of Early Detection of Alzheimer’s Disease via Multidimensional Analysis of Longitudinal Magnetic Resonance Scans
Statistics show that two per cent of Canadians aged 60-74 years, and one-third over the age of 85, suffer from Alzheimer's disease and related dementias. By 2031, more than 750,000 Canadians are expected to have Alzheimer's disease and related dementias. The social and financial costs of managing people with these conditions is significant and puts a severe strain on families and on the health system. Sadly, by the time Alzheimer’s symptoms are recognized and confirmed, there is often substantial irreversible neurodegenerative damage. Current methods of diagnosing Alzheimer’s disease are frustratingly inexact. Lacking ways to identify the onset of disease within the brain itself, clinicians instead look for telltale symptoms, such as failing memory. Even when the disease has progressed and structural changes become apparent on magnetic resonance imaging (MRI) scans, neurologists do not have tools to precisely measure how advanced the disease is, relying instead on visual inspection. Dr. Faisal Beg is trained in engineering, biology and mathematics. Drawing from international MRI databases containing the brain scans of hundreds of older adults with and without Alzheimer’s, he is taking precise measurements to pinpoint where and how brain structures change with the onset of the disease. It’s a complex analysis, made even more challenging due to the normal variations seen in brain shape, size and structure. Beg anticipates that his research will help take the guesswork out of diagnosing Alzheimer’s disease, especially in its early stages. In the longer term, it also may contribute to more accurate assessments of whether new Alzheimer’s drugs are effective in slowing or halting progression of the disease