In the development of a vaccine against four strains of the human papilloma virus (HPV), of particular note were studies involving innate immune response when genes of the virus were introduced into host cells. It was observed that increased levels of antibodies were produced by inoculation that used synthetic versions of two HPV genes. The application of gene vaccines, not only for cancer immunization, but also to aid the treatment of infectious diseases, is an ongoing and very active area of study. Developing an efficient and reliable method to produce synthetic DNA is a necessary tool for these studies to succeed. Due to the inherent difficulty of creating long strands of DNA, current technologies for gene synthesis use computational methods for design of shorter DNA fragments called oligos (oligonucleotides), which can be reliably synthesized and assembled. However, ensuring a set of oligos will self-assemble correctly into a longer DNA strand is difficult and complex, and previous software programs have failed to solve this issue. Chris Thachuk is a computer scientist who develops synthetic gene design algorithms. He and his colleagues are developing algorithms to successfully assemble long strands of DNA from oligos. These new algorithms outperform the current state-of-the-art and their effectiveness has been demonstrated through computational experiments on a large set of genes. Three average size genes have been produced with the aid of these algorithms. He now intends to build upon this success by extending the algorithms to produce reliable designs for synthesizing long genes and for synthesizing multiple genes in one step. By providing researchers with more advanced algorithms and accurate modeling software for gene synthesis, Thachuk hopes to contribute to new insights for treatment, detection and/or prevention of diseases.
Research Location: University of British Columbia - Point Grey
Investigation into the factors mediating embryonic muscle migration in Caenorhaditis elegans
During embryonic development, precursor muscle cells (myoblasts) are generated in one region of the embryo and then dispersed throughout the body. These migrations are controlled by external signals that guide the migrating cells. Previous muscle research has identified genes for muscle differentiation and development, but the important genes regulating muscle cell migrations have are unknown. Muscle cell migration is of particular importance for a new treatment called myoblast transfer therapy, which is being developed to treat muscular dystrophy and hearts damaged by cardiac arrest. The treatment injects healthy myoblasts into the damaged area in order to repair the affected tissue. A key problem in this treatment is that, for both cardiac and muscle tissue, the myoblasts fail to migrate properly and effectively colonize the damaged area. Ryan Viveiros is studying the embryonic development of a small nematode worm called Caenorhabditis elegans. While substantially simpler than humans, these worms also have muscle and share a number of the same genes required for muscle development as mammals. Because the worm embryos develop inside clear eggs, Viveiros can record the developing embryo and watch the cell migrations in real time. Computer software then allows him to follow the cell migrations and determine which cell types are defective. Viveiros will search for the genes that cause improper muscle migration and determine where these genes are turned on in the embryo. In addition to determining the basics of how muscle migration occurs, Viveiros hopes his findings could lead to new insights for improving myoblast transfer therapy. In addition, because this research is also relevant to cell migration in general, his findings may also inform our understanding of how cancer cells migrate (metastasize).
Is Transcranial Magnetic Stimulation a Useful Clinical Adjunct for Predicting Stroke Occurrence and Severity following Transient Ischemic Attack? A Prospective Cohort Study
Stroke continues to be one of the leading causes of death, long-term adult disability, and illness in Canada. Approximately 1/4 of ischemic strokes are preceded by a brief episode of neurological deficit, or transient ischemic attack (TIA). During a TIA, individuals experience stroke-like symptoms that rapidly disappear. Early stroke risk in patients with TIA is considerable and North American population-based estimates of recurrent stroke range from 9.5% at 90 days, to 14.5% at 1 year. These data highlight the importance of intervention for secondary stroke prevention. However, efforts to estimate stroke risk using clinical profile and diagnostic imaging have shown variable predictive value and validity. Therefore, new markers are needed to help clearly identify high risk individuals and improve current stroke prevention strategies. Jodi Edwards is studying if cortical motor excitability, measured using a brain stimulation technique called Transcranial Magnetic Stimulation (TMS), is a marker of increased stroke risk in individuals with TIA. TMS provides information about the activity of different types of neurons in the brain and with this research, she will determine if there is an association between altered thresholds of intracortical inhibition in the cortical hemisphere affected by TIA and stroke occurrence. In addition, she is also investigating if larger asymmetries in intracortical thresholds are predictive of increased clinical severity in stroke subsequent to TIA. This research has the potential to significantly advance the understanding of the mechanisms underlying TIA and provide a new technique for the identification of high-risk patients following a TIA. Ultimately, this study has the potential to improve stroke prevention strategies and reduce recurrent stroke risk in patients with TIA.
The effects of Sildenafil on cardiac and lung function in heart transplant recipients during exercise
While heart transplant recipients have significantly improved tolerance for exercise post-transplant, their aerobic exercise capabilities remain 40 – 60 per cent below normal. Blood vessel dysfunction, skeletal muscle wasting, and surgical severing of the nerves to the heart have all been implicated as factors contributing to reduced aerobic capabilities in individuals following heart transplantation. Heart transplant recipients also have dramatic pressure increases in the blood vessels within their lungs during exercise. These abnormally high pressures may result in heart dysfunction and breathlessness, causing impaired exercise tolerance. The drug Sildenafil has been shown to reduce pressure in the blood vessels of the lung. Previous research has shown that Sildenafil improved heart function during exercise among heart failure patients. Ben Esch is investigating whether Sildenafil is also beneficial to heart transplant recipients during exercise. He is testing aerobic exercise capacity among 20 heart transplant recipients both with and without Sildenafil — assessing their heart function (using cardiac ultrasound) and oxygen uptake. The results from this investigation may have important implications for cardiac rehabilitation in heart transplant recipients. If Sildenafil is shown to have a positive effect on cardiac function and exercise tolerance, its use could help heart transplant recipients train at higher intensities for longer duration during their exercise rehabilitation.
Neuroimaging and quality of life of children with developmental coordination disorder
Developmental coordination disorder (DCD) affects six to 15 per cent of children aged five to 11. In BC, up to 48,000 of children may meet the diagnostic criteria for DCD. Children with DCD have significant motor coordination difficulties that interfere with their academic achievement and/or activities of daily living. While it was once believed that children with DCD would outgrow their motor difficulties, research suggests that these difficulties persist into adolescence and adulthood. Individuals with DCD tend to avoid social and physical activities, are at higher risk for obesity and coronary vascular disease, and experience social and emotional difficulties. There is some suggestion that DCD is related to differences in brain development, but this has yet to be confirmed. No studies have been conducted to determine how the brains of children with DCD differ from those of typically developing children, and few studies have explored the quality of life of children with this disorder. Jill Zwicker is exploring the neurobiological explanations for children with DCD, and studying how DCD impacts their quality of life. She is examining patterns of brain activation of children with and without DCD using neuroimaging techniques to determine differences in brain anatomy and activation during a fine-motor task. Zwicker will also be interviewing school-age children with DCD to determine how the disorder affects their quality of life. Zwicker’s findings will be used to educate physicians and therapists in BC and beyond regarding DCD. In the longer term, these efforts will lead to the development of scientifically grounded rehabilitation approaches specifically targeted towards enhancing brain activity, function and quality of life for children with DCD.
When does culture make a difference? Exploring the influence of culture in palliative and end of life care
Canada has a large and growing multicultural population with different perspectives on health and illness. This brings unique challenges to the provision of appropriate palliative and end-of-life care, where culture is known to influence communication patterns, decision-making styles, responses to symptoms, treatment choices, and emotional expression at end-of-life. Previous studies have shown that unresolved cultural differences can result in poor interactions and outcomes in end-of-life care. Although culture is known to be an important influence in health care, little is known about when and how people apply their cultural beliefs, values and practices to their health care experiences. Theories suggest that people often move back and forth between their traditional culture and mainstream culture to meet different needs. Harvey Bosma is exploring the ways in which culture influences interactions between culturally diverse patients and health care professionals in palliative care. He will use qualitative interviews and participant observations to develop rich and in-depth descriptions of these experiences from the perspective of a range of culturally diverse participants. Bosma’s findings will provide valuable insight into when and how culture facilitates or challenges health care interactions. The information can be used by physicians, nurses and other health care professionals to better understand the needs and actions of culturally diverse patients. Ultimately, the findings of this study may be used to enhance culturally-competent and sensitive care at end-of-life so that palliative and end-of-life care is relevant and accessible to individuals and families of different cultures.
Barriers to methadone maintenance therapy access in British Columbia
Methadone maintenance therapy (MMT) is the most widely used and well-researched treatment for opioid dependency in Canada. MMT is regarded as an essential means to overcoming the health, social, and economic harms associated with opiate addiction, including preventing new HIV infections, reducing mortality, criminal activity, syringe sharing and unprotected sex. British Columbia was the first worldwide to launch a methadone program, and has long represented a model of excellence in MMT provision. However, barriers to MMT access continue to occur, particularly among Aboriginal people and the most marginalized members of society. The number of patients receiving MMT has declined since 2002, in spite of a reported unmet need for MMT provision. Canadian health care providers and the patients they serve continue to regard MMT as a controversial treatment. At the root of the concern may be feelings by patients that their needs are not being met, barriers with patients’ ability to carry on with their lives and access other treatments, and differences in treatment goals between patients and health care providers. Azar Mehrabadi is investigating policies, attitudes and access related to MMT provision in BC. She is conducting interviews with family physicians and the patients they care for from private and public clinics across BC, drug user advocacy groups, decision-makers, and MMT regulatory body representatives, and gauging their attitudes and beliefs around optimal MMT outcomes. Mehrabadi’s work has important implications for health policy related to addiction, infectious disease prevention, and primary health care provision for marginalized populations in Canada. In particular, best practices for MMT delivery in BC have an important influence on addictions health policies in the rest of Canada and the United States.
Social support groups as a means to enhance the health literacy status of ESL-speaking immigrant women
Health literacy is defined as the ability to read and comprehend prescription bottles, appointment slips, and other essential health-related materials, or the capacity to obtain, interpret and understand basic health information and services needed to make appropriate health decisions. Inadequate health literacy increases a person’s risk of dying of chronic and communicable diseases, and directly affects the ability to follow physician instructions, to understand disease-related information, and to understand health care rights. In particular, immigrant women may struggle to understand health information. On average, they have lower literacy rates than immigrant men and they also have significantly lower literacy levels than the Canadian-born population. There is a social dimension to health literacy, but no study to date has investigated whether or how social support can moderate the effects of health literacy on individual health and health service use. Laura Nimmon is partnering with an immigrant society in BC to implement a community health education program that fosters social relationships for ESL-speaking immigrant women and builds on their health literacy levels. She is creating a pilot program that will educate research participants about health information and guide them to act as community health advisors to their peers, mentoring other immigrant women to participate in healthy choices and activities. Nimmon’s research aims to improve understanding about how peer-based social support groups might enhance the health literacy status of immigrant women and alleviate the adverse health consequences of low health literacy.
Determining the effects of monoaminergic regulation of frontostriatal systems in different aspects of impulsive decision-making.
Impulsivity is a characteristic of human behaviour that can be both beneficial and detrimental in our everyday lives. An impulsive decision can allow us to seize a valuable opportunity, or to make an ill-considered choice that we live to regret. High levels of impulsivity are not only considered socially unacceptable, but they are a key symptom in a range of psychiatric illnesses including bipolar disorder, attention-deficit hyperactivity disorder (ADHD), pathological gambling, personality disorders and substance abuse. Understanding the neurobiological basis of impulsivity could provide valuable insight into these afflictions and potentially lead to the development of new treatment and therapeutic approaches. Dr. Catharine Winstanley is exploring the role of different regions of the brain on aspects of impulsive decision-making and gambling. One of the most commonly-used measurements of impulsive decision-making in human volunteers is the Iowa Gambling Task (IGT), in which subjects try to accumulate points by choosing from options associated with varying net gains or losses. Winstanley successfully developed a model of the IGT for use in rats, allowing her to measure their cognitive processes. She is also determining whether changing levels of brain chemicals, such as dopamine and serotonin, can affect impulsive choice, and whether these chemicals activate similar molecular pathways in neurons that can alter brain function and behaviour.
Causal Attributions and Self-Conscious Emotions in Coping with Alcoholism
Although there are large individual differences in recovery rates from alcoholism, little is known about the emotional factors that underlie these differences. Studies suggest that shame and guilt, two negative self-conscious emotions (emotions that require self-evaluations), may have divergent effects on a range of health outcomes. Specifically, shame promotes a range of negative outcomes, such as depression, whereas guilt has more positive effects, including empathy and high self-esteem. In addition, two distinct kinds of pride — “authentic” and “hubristic” — may also have divergent effects. Dr. Jessica Tracy is researching the influence of these four emotions on recovery from alcohol addiction. She is testing whether newly-sober members of Alcoholics Anonymous (AA) who experience guilt and authentic pride, rather than shame and hubristic pride, enjoy greater health and recovery benefits over time. Tracy is also testing whether the thought processes that promote these emotions contribute to health outcomes, and if so, whether specific self-conscious emotions account for these effects. This research is unique in its emphasis on self-conscious emotions, which may play an important role in addiction. The findings could lead to new treatment methods for clinicians, such as targeting these important emotions.