The prevalence of obesity is increasing dramatically, and is occuring at an increasing rate among children. Obesity is a major risk factor for numerous diseases including diabetes, heart disease, high blood pressure, stroke, arthritis, and some forms of cancer. Inherited factors strongly affect an individual’s risk for becoming obese, especially in an environment with little exercise and diets high in fat and sugar. However, many of these genetic factors are not yet known.
Dr. Susanne Clee’s research seeks to identify one of these genetic factors. She is conducting genetic studies on mouse strains that differ in their risk of developing obesity when fed a high fat diet. Clee will progressively zero in on new candidate genes by comparing the suspected region’s DNA sequence between obese and non-obese mice, and identifying specific changes in genes that could lead to the development of obesity. At the same time, Clee will use these mouse strains to study the biology of how obesity develops. By comparing mice that become obese when fed a high fat diet compared to mice that resist obesity, she will be able to describe how the body's processes are altered as individuals become obese.
By identifying new genetic factors that cause mouse strains to become more obese, Clee hopes to gain a more specific understanding of how obesity develops. This knowledge will lead to new ways to treat or prevent this disease and to identify those individuals more at-risk of developing obesity.
Low-speed rear-end collisions can generate whiplash injuries, especially when the victim is unprepared for the collision. Neck pain is the most frequent symptom experienced by victims of a car collision, and up to 30% of people injured in a car collision will develop chronic symptoms. In fact 6% of people who develop chronic whiplash from a collision have not returned to work 12 months after the injury. The precise cause of whiplash is not known, but an overreaction in unprepared individuals — known as a startle response — along with the sudden recoil movement of the head, is thought to damage the joints and muscles of the neck.
As an MSFHR-funded post doctoral fellow, Dr. Jean-Sébastien Blouin conducted research that suggested the presence of a startle response when people are exposed to low-speed rear-end collision. Now he is investigating whether the startle response is linked to stimulation of the deep neck muscles, and if activation of these muscles during a collision may increase the risk of injury. With volunteers acting as “crash test dummies,” Blouin is simulating very low speed (1.8 km/hour) collisions to observe their startle response and measure the corresponding muscle activity. He’s investigating the link between a strong startle response during a low speed collision and the development of whiplash symptoms. He’s also exploring if stimuli delivered immediately prior to the collision can inhibit the startle response, possibly providing protection against injury. Findings could contribute to development of a warning device in cars that will help prevent whiplash injuries.
Electrical disturbances in the heart are a serious health threat for many people. For example, cardiac atrial arrhythmias (a type of irregular heart beat) affect 4% of people aged 60 and older, and have an associated fivefold increase in stroke. As our population ages, this incidence is expected to increase up to 2.5 times over the next half century. Cardiac membrane proteins called ion channels control the flow of sodium and potassium in and out of heart cells, regulating both the cardiac electrical impulses and the contractions associated with the heart beating. Dr. Christopher Ahern is interested in drugs that interact with the sodium ion channel to correct atrial arrhythmias. Although these drugs are widely prescribed, scientists still don’t fully understand exactly how they work. More critical is that these drugs can become lethally toxic in cases where the arrhythmia co-exists with other common heart problems, such as an enlarged heart. This dangerous shortcoming seriously limits their use for many people who could otherwise benefit from their therapeutic effects. There is a need for better anti-arrhythmic therapies – ideally, designer drugs for atrial arrythmias that exploit the positive attributes of current therapies while minimizing their negative side-effects. Dr. Ahern is using new chemical methods that are providing much more detailed information about how these drugs bind to and interact with the sodium channel. Using these new methods in combination with computational approaches that bypass previous limitations with the research, his team will take a fresh look at drug binding and ion channel function with the goal of designing safer anti-arrhythmic drugs
Physical inactivity in adolescence has been linked to a vast array of physical and mental health problems that extend across the lifespan. Canadian adolescents are required to undertake regular physical education as part of their school curriculum, guided by physical education teachers. However, more than half of adolescents are considered not sufficiently active to meet international guidelines for optimal growth and development. In workplace settings, “transformational leadership” is exemplified by business leaders whose behaviours and interactions inspire employees to reach new heights of work performance and self confidence. Transformational leaders inspire, energize and intellectually stimulate their followers. Training programs in business and military settings have also shown that people in leadership positions can successfully acquire and develop these behaviours.
Exercise and health psychologist Dr. Mark Beauchamp is taking this leadership model out of the workplace and applying it to school physical education and health promotion settings. He’s studying whether training physical education teachers in transformational leadership can positively affect the attitudes and behaviours of their students around adopting and maintaining physical activity. If this approach is proved effective, this research could be used to help develop evidence-based initiatives (across Canada and beyond) that inspire a greater proportion of adolescents to become and stay physically active.
With the ever-increasing prevalence of antibiotic resistance, it has become critical for scientists to develop alternatives to antibacterial agents and offer long term sustainable health care solutions. Bacterial resistance to common antibiotics has a dramatic impact on hospital and community health care, affecting entire hospital wards and communities. This creates significant – and largely avoidable – pressure on current health care budgets. Two types of microbe-fighting peptides are generating much interest as potential alternatives to current antibiotics: cationic antimicrobial peptides (CAPs) and anionic lipopeptides (ALs). Both types of peptides are commonly found in nature and have remained effective, displaying little to no antibiotic resistance effects. Both are believed to act by targeting and perturbing the bacterial membrane, which eventually leads to cell death – a process that is strikingly different from current antibiotics. Dr. Suzana Straus aims to find novel alternatives to current antibiotics by investigating how promising candidates from the CAP and AL peptide families function and by designing more potent versions derived from these candidates. Her work is focused on three peptides: two CAPs from amphibians and one AL called daptomycin, which is known to be effective against particular complicated skin infections. Straus is researching the structural and functional properties of these membrane-associated peptides and proteins, which is crucial in the design and development of new and effective medicines. Ultimately, her work will provide insight into which factors should be considered in the design and development of a new generation of antibiotics.
Syphilis, caused by the bacterium Treponema pallidum, is a chronic bacterial infection with a global distribution. Although this sexually transmitted disease is 100 per cent curable with penicillin, syphilis remains a health threat, with an annual incidence rate of 12 million active infections. In BC, new cases are being reported at almost double the national rate. Unchecked, the infection can damage every tissue and organ in the body, including the brain. Equally troubling, syphilis infection drastically increases vulnerability to HIV infection. Treponema pallidum is a highly invasive pathogen; following attachment to host cells, the organism invades the tissue barrier and enters the circulatory system, resulting in widespread bacterial dissemination. Little is currently known about the mechanisms this bacterium uses to initiate and establish infection.
Dr. Caroline Cameron has the only laboratory in Canada conducting basic research on this bacterium. She is using cutting-edge proteomic technologies to study two molecules that enable the bacterium to attach itself to host cells lining the bloodstream – a critical step in the development of infection. By understanding these mechanisms, Cameron hopes to identify potential ways that scientists could interfere with adhesion and disrupt the infection process. Ultimately, her work could lead to development of a vaccine to prevent syphilis.
The number of Canadians older than 65 is steadily increasing, a trend that will continue over the next few decades. The prevalence of age-related disorders such as dementia is also increasing, along with the related need for personal care and treatment. Cognitive impairment adversely affects quality of life in late adulthood, limiting independence and survival. To examine these important health issues, Dr. Stuart MacDonald is studying factors related to age-related declines in cognitive performance. Part of his research employs existing data from a Swedish study (the Kungsholmen Project; http://www.kungsholmenproject.se/) to examine patterns and identify early predictors of cognitive decline. As the average age of the Swedish population far exceeds that of Canada, research on the Kungsholmen data may provide important insights that can help inform Canadian healthcare policy and prevention strategies.
Dr. MacDonald is also researching how performance for select measures of memory and intelligence is influenced by cognitive training across a period of weeks, as well as regular aerobic exercise (walking three times per week for 30 minutes) over a period of months. Dr. MacDonald's goal is to clearly demarcate the stages and transitions of cognitive decline from mild age-related impairment to more severe dementia deficits. This will help identify early warning signs of cognitive impairment from a broad range of predictors. The findings could lead to more effective prevention based on knowledge of these risk factors, including campaigns to promote health-smart behavior.
The nature of the relationship between a healthcare provider and an individual receiving care has an impact on the success of psychotherapy and drug therapy. A strong professional working relationship can not only enhance the effect of psychological and psychiatric interventions, but can be therapeutic in and of itself. This has even been found in the treatment of very serious psychiatric conditions such as bipolar disorder and schizophrenia. Researchers have estimated that as least 30% of the effectiveness of psychotherapy and drug therapy can be accounted for by the quality of the professional relationship between an individual and his/her mental healthcare provider. There is a lack of understanding about the factors that are most important for developing a solid working relationship from the perspective of the individuals receiving the mental health services. Expanding upon research he conducted as a MSFHR trainee, Dr. Robinder (Rob) Paul Bedi is exploring this area. He is interviewing individuals currently receiving mental health services and analyzing the variables that they identify. The result: identifying the most common factors found to be essential in the development of positive therapeutic relationships. Bedi’s research aims to help mental healthcare providers develop strong working relationships with the individuals they treat, resulting in improved overall effectiveness of the mental health services that individuals receive.
A recent report from the World Health Organization revealed that about 1.5 million people died from TB in 2006. In addition, another 200,000 people with HIV died from HIV-associated TB. Current strategies aim to reduce the annual death toll from TB to less than 1 million worldwide by 2015, as set out in the United Nations Millennium Development Goals. Infection by the Mycobacterium tuberculosis microorganism causes TB. The current global strategy for TB control is based on reducing the spread of infection through massive vaccination campaigns with the BCG (bacille Calmette-Guérin) vaccine, and treatment of individuals with active disease using multi-drug combinations. However, there are challenges to this approach, including inefficiency of the BCG vaccine, the emergence of drug resistant strains of Mycobacterium tuberculosis (Mtb) and the difficulty in delivering a treatment that requires multiple drugs over periods of six months or more.
Until recently, little was known about how Mtb alters the host immune system to cause infection. Through Dr. Zakaria Hmama’s work as an MSFHR Scholar over the past six years, important new knowledge has been developed regarding the sub-cellular and molecular mechanisms of host/pathogen interactions. His research over the next five years will focus on gene manipulation technologies to upgrade the current BCG vaccine with recent immunological concepts to maximize its protective properties. Hmama is also investigating an important virulence factor identified by his lab as a potential drug target for TB treatment.
Cancer is one of the leading causes of death in Canada. As a pathologist, Dr. Torsten Nielsen’s job is to accurately diagnose cancer and determine its type from more than 200 possibilities. For more than 50 years, these diagnoses have been made using a light microscope to examine tissue biopsies. However, this can be subjective, requiring the pathologist to make a judgment call in certain cases. Recent new technologies help determine the genetic profile of each type of cancer. This profile can be used to distinguish between cancers that otherwise appear almost identical under the microscope. The ability to detect subtle differences among cancers can be enormously important because the exact diagnosis determines what combination of surgery, radiation, hormone treatment or chemotherapy is the best treatment plan.
Using advanced genetic tools, Dr. Nielsen aims to develop clinical tests that more accurately identify difficult subtypes of cancer, and to then determine which treatments will work best for each subtype. Previously supported by an MSFHR Scholar award, he works with two cancer types in particular: breast cancer and sarcomas (tumours of muscle and bone). With breast cancer, he is working to develop inexpensive and easy-to-conduct clinical tests that accurately diagnose four types not easily distinguished under the microscope. With sarcomas, he is using new molecular tools to develop diagnostic tests and treatments that target specific molecular changes, to see if new drugs can cure these cancers with minimal side effects. His research could lead to simple, effective, and widely available diagnostic tools and personalized treatment strategies that will improve survival for cancer patients.
