There is growing recognition that many diseases and disorders, such as asthma, joint and tendon disorders, communicable diseases and some cancers can be caused, or aggravated by workplace exposures. Occupational health is one area where the translation of research findings into new policies and increased safety in the workplace can have an immediate and profound effect on work-related injury and disease. This process, known as knowledge transfer and exchange (KTE), involves the use of research knowledge in decision-making – for individuals setting workplace safety policy, managers supervising a workforce, or employees making decisions regarding risks in the workplace. While there is widespread recognition of the importance of communicating research knowledge to those who can benefit from it, there has been little research on the KTE process within occupational settings, and how this information can be effectively communicated outside academic circles. Research that focuses on KTE as a joint effort – where the expertise of both scientists and workers is considered and recognized – has yet to be examined within occupational settings. Dr. Anne-Marie Nicol is researching the process and context by which occupational and environmental research knowledge is exchanged from research scientists to policy-makers and to employees in the workplace. Her work includes analyzing the methods that occupational and environmental scientists use to promote their research knowledge, and examining what types of information the public and policy-makers use to make decisions about risk in the workplace. This research will help develop strategies to facilitate the effective exchange of research knowledge in a timely manner to people at risk from occupational and environmental exposures, and help ensure that the information people receive is useful and appropriate to their needs.
Research Location: University of British Columbia - Point Grey
Examining predictors of health behaviors across the life span
According to the World Health Organization, six out of the top seven risk factors for chronic illness are associated with a lack of physical activity, smoking and unhealthy eating habits. Adolescence is a critical period for establishing attitudes and behaviours associated with physical activity, eating, and tobacco use, yet little is known about the relationships among the health behaviours and the reasons for initiating or avoiding them. As a result, understanding and targeting adolescent behaviour can potentially have an important impact on health status across the lifespan. Catherine Sabiston is studying what influences adolescents’ decisions to engage in healthy or unhealthy behaviours. She is reviewing several social, cultural and individual factors—such as social support and relationships, gender-stereotypes, socioeconomic status, self-perceptions, competencies and values—that affect physical activity, eating and tobacco use. Catherine is also interested in how these factors affect boys and girls differently, and whether these factors influence adolescents of a variety of ethnic backgrounds differently. This research should help explain the onset of and relationships among multiple health behaviours. Catherine will use this information to develop a school-based intervention program to target health behaviour change in adolescents, with the goal of developing realistic recommendations towards improving the long-term health status of Canadians.
Substrate spectrum of matrix metalloprotease-2 in physiology and pathology
Matrix metalloproteases (MMPs) are a family of extracellular proteases (enzymes) which reside outside cells and initiate the breakdown of proteins that mediate cellular signals. Processing by MMPs can activate, deactivate, or functionally convert signaling proteins. Within the MMP family, MMP-2 plays a pivotal role in cancer spread, since collagen IV degradation by MMP-2 allows tumor cells to penetrate the surrounding tissue. While MMP-2 is an attractive drug target for cancer treatment, clinical trials have shown that drugs which interfere with this enzyme cause severe side effects, partly because the protease is believed to play a part in so many other cell functions. Dr. Oliver Schilling is using innovative proteomic tools to identify and characterize novel MMP-2 substrates on a system-wide scale. His project aims to identify the abundant variety of natural substrates of MMP-2 as well as to the roles of MMP-2 and the cellular signaling pathways that the protease regulates. Given the prominent role of MMP-2 in tumor development, this knowledge has the potential to assist in the development of cancer drugs which are more effective and have fewer side effects.
Developing a Chlamydia trachomatis vaccine by optimizing dendritic cell responses
Chlamydia trachomatis is the most commonly reported sexually transmitted infection (STI) in Canada. In BC alone, there were 7000 cases reported in 2003. Although antibiotic treatment is effective, more than half of all infections escape detection and timely treatment because they are asymptomatic in the early stages. Left untreated, the infection can lead to chronic pain and infertility. The development of an effective vaccine to prevent C. trachomatis infection is an urgent public health priority. No vaccine has been developed for C. trachomatis since an inactivated whole cell vaccine failed in trials in the 1960s. In order to better understand how the immune system responds to the bacteria and to develop candidate vaccine preparations, Dr. Michelle Zaharik is using cutting edge immunological and gene array technologies to probe how the immune system responds to C. trachomatis. She is looking particularly at dendritic cells (DCs) which play a role in activating the immune system to mount a defence against invading pathogens and are the subject of intense interest for vaccine development. Michelle’s study will identify the specific DC responses necessary to develop protective immunity against C. trachomatis. Ultimately, this may contribute to the development of vaccines specifically targeted to preventing chlamydial infections.
Structural and biochemical analysis of the essential type III secretion system ATPase from Gram-negative pathogenic bacteria
Infection by gram-negative bacteria is a growing threat to humans, animals and plants. The severity of disease and death rate associated with these infections continues to grow because of the increase in antibiotic-resistant strains of these bacteria, including strains of Yersinia, Shigella, Salmonella, Pseudomonas, Chlamydia and enteropathogenic Escherichia coli (EPEC). In several of these organisms, disease-causing properties are dependent upon a type III secretion system (T3SS). The T3SS is a complex of more than 20 unique protein components structured into a syringe-like apparatus, which delivers the virulence factors (toxins) from the bacteria directly into the host cells. A key component for toxin insertion is the activity of a type III ATPase, an enzyme that provides the energy for this process and acts as a gatekeeper on the bacterial inner membrane. Dr. Raz Zarivach’s goal is to determine the first three-dimensional molecular structure of this type III ATPase and further understand its mechanisms and role in virulence. He hopes his work will lead to the design of new drugs that will inhibit this secretion system and protect against these common disease-causing bacteria.
Exploring and addressing dimensions of health in older children with perinatally-acquired HIV-1 in British Columbia in partnership with communities
Effective antiretroviral therapies are enabling children born with HIV in developed nations to mature into adolescence and young adulthood. These children represent a unique group in the global HIV epidemic, because they have developed throughout their lives with access to antiretroviral drugs. Few Canadian studies to date have examined the lives of these children. As HIV-positive children mature, they face new medical and social challenges, and additional age-appropriate services are needed to support their development. For her MSFHR-funded Master’s work, Sarah Fielden explored the needs of older BC children born with HIV, in collaboration with the children, their family members, and their health care and community service providers. Now, Sarah’s goal is to develop health promotion programs to promote healthy development among these children. Sarah brings previous experience working with young people living with HIV in Zimbabwe, Africa, to this community-based study. She will also assess mortality, drug treatment trends and demographic profiles of BC children with HIV. The lessons learned from this research may be of interest to those working with children with other chronic diseases and the international HIV community at large.
Spatial assessment of forest fire smoke exposure and its health effects in the southern interior of British Columbia during the summer of 2003
The forested mountains and dry valleys of British Columbia’s southern interior make this region susceptible to summertime wildfires. During the unprecedented 2003 season more than 6,900 fires destroyed 343 homes, consumed 260,000 hectares, and exposed up to 640,000 residents to potentially harmful levels of smoke. Forest fire smoke has several similarities to urban air pollution. Both include tiny, airborne particles that can irritate the lungs and place stress on the entire cardio-respiratory system. However, since forest fires usually burn in sparsely populated areas with limited air quality monitoring, it has been difficult to determine whether smoke particles carry the same health risks as their urban relatives. Sarah Henderson is using computer simulations in combination with satellite data to estimate the daily smoke exposure of southern interior residents between July 1st and September 30th, 2003. She will correlate her results with regional hospitalizations to determine how the risk for respiratory and cardiovascular disease is affected by exposure to forest fire smoke. This study will help to explain the health effects of fire smoke and Sarah hopes that it will influence forest management policy in the future.
Differential modulation of T-type calcium channels by metabotropic glutamate receptors
Proteins called calcium channels regulate when and how much calcium gets into nerve cells. In humans, calcium channels control a variety of normal physiological responses including muscle and heart contraction, hormone secretion, and the way neurons transmit, receive and store information in the brain. When too much calcium enters cells through calcium channels, a number of disorders can result, including congenital migraine, angina, epilepsy, hypertension and stroke. Michael Hildebrand is studying the interactions between the most recently identified family of calcium channels (T-type channels) and a membrane receptor called the mGluR receptor. This receptor is activated by the neurotransmitter glutamate and triggers internal chemical signals within neurons. T-type channels and mGluR receptors are highly expressed in the same cell types in various brain areas and both proteins are shown to be involved together in various physiological processes. Michael’s research will specifically contribute to better understanding of how mGluR receptors are able to selectively turn on and off specific members of the T-type calcium channel family. Results will lead to further understanding of brain development, normal brain functions such as learning and memory, and abnormal functions such as epilepsy.
Characterization of the interaction between the endocannabinoid system and pharmacological antidepressants
Depression is a devastating mental disease that affects up to 10% of the population. Its neurobiological basis is unknown. Traditionally, depression was thought to be caused by a deficiency in the monoamine neurotransmitter molecules, such as serotonin. Based on that assumption, antidepressant drugs were developed to prevent the breakdown of monoamines. However, recent advances in neuroscience have demonstrated that the effects of antidepressants on monoamine levels are immediate, whereas actual changes in mood take many weeks, which means the ability of antidepressants to effectively treat depression is likely due to long term changes in other systems. There is growing evidence linking depression to the endocannabinoid system – a group of molecules and their receptors that act as a modulatory system, fine-tuning the body’s responses to a variety of stimuli. Various studies have suggested that endocannabinoids may be reduced in depression and that use of antidepressants may act to increase them. Mathew Hill is examining the relationship between endocannabinoid and antidepressants. He is specifically interested in determining if increasing endocannabinoid activity is a common response to all types of antidepressants; if changes in the endocannabinoid system are required for antidepressants to work; and if increasing endocannabinoid activity alone is sufficient to elicit an antidepressant response. Results from his study will contribute to a better understanding of the neurobiology of depression and ultimately may lead to a new class of antidepressants.
Identification of sialyltransferase inhibitors and their use in the development of a chemical genetics tool for the study of normal and pathological cell surface carbohydrate modification
The complex arrangement of carbohydrates that cover the surfaces of cells is known to play a key role in biological processes ranging from cellular recognition to gene regulation. Changes in the composition of these carbohydrate structures are linked to the onset of many diseases, including the proliferation of cancer cells and compromised immune function. Research suggests that these changes are often associated with elevated activities of the enzymes responsible for sugar placement. As such, these enzymes (glycosyltransferases) represent an attractive drug target for the treatment of many human diseases. Unfortunately, multiple enzyme forms for a given sugar transfer are encoded by the human genome and the role that individual genes play in both normal and pathological cell surface modification remains largely unknown. Luke Lairson’s goal is to identify the small molecules that inhibit the activity of a class of glycosyltransferases known as sialyltransferases. These enzymes are responsible for adding a particular type of sugar known as sialic acid (known to play a key role in many types of cancer) to cell surfaces. Luke hopes that identifying these small molecules will serve as a potential starting point for the development of a new class of anti-cancer drug. His results may also be used to develop a technology for the identification of individual gene products responsible for the placement of particular sugars in both normal and diseased cells at a given point during development.