Much of British Columbia’s forests have been infested with the mountain pine beetle (MPB), an epidemic that is predicted to result in the loss of more than 80 per cent of the province’s pine forests by 2013. The MPB is also expected to result in the widespread loss of jobs, shifts in traditional resource cultures of affected communities, and an increased risk of forest fires and other natural disasters (e.g. slides, flooding). Gender is recognized as one of the most critical determinants of disaster-related vulnerability. Women and children are disproportionately affected by disasters, reporting higher rates of stress-related health problems (e.g., post-traumatic stress, anxiety, depression), an increased risk of sexual and domestic violence, greater economic marginalization, and substantial increases in their work. They are also less likely to be involved in community-based planning and decision-making processes. Dr. Robin Cox is analyzing individual and collective stressors associated with MPB in four forestry-dependent communities: Barriere/Louis Creek, Clearwater, Quesnel and Wells. She is piloting a community-based research strategy intended to engage affected residents in each community in a series of workshops and focus group interviews. The focus of these events is to identify and elaborate community-based definitions and strategies of resilience that reflect the specific cultural, social, and political contexts of participants. The proposed study will contribute to the development of knowledge around community resilience that integrates a gender perspective, and will lead to the development of policies and procedures that are relevant and responsive to different communities affected by MPB.
Program: Trainee
Unleashing the research potential of a population-based data system: integrating community-centred, life-course, linked-data, and longitudinal approaches to monitoring child health and development
Early Child Development (ECD) – the development of physical, social-emotional, and language-cognitive capacities in the early years – is recognised as having life-long effects on health, well-being, behaviour, and skill acquisition. Population-based ECD research is essential for understanding the capacity of our future population. British Columbia is at the forefront of population-based research in ECD, thanks to a rich database created by the Human Early Learning Partnership (HELP) at the University of British Columbia. Here, health scientists can access population-based data on children’s health and development, and link these data to other administrative and research databases, such as Statistics Canada’s neighbourhood-level census file. Making use of these state-of-the-art data resources, Dr. Jennifer Lloyd is exploring the pathways of early developmental experiences to later educational outcomes, the relationship between children’s developmental trajectories and their neighbourhoods of residence, and the patterns in which children’s health and development present themselves as gradients when assessed against the socioeconomic characteristics of their residential neighbourhoods.. Lloyd’s research will explore inequalities in children’s developmental trajectories in an unprecedented fashion in British Columbia. In terms of policy and practice, her research stands to influence health delivery systems by providing evidence to guide public health and social policies and program development, and to assist in reducing gaps in existing patterns of children’s development and educational outcomes in British Columbia and beyond.
Novel characterization of a G-protein coupled receptor, Autocrine Motility Factor Receptor (AMFR): an endoplasmic reticulum-localized E3 ubiquitin ligase
The endoplasmic reticulum is a membrane network within cells involved in the synthesis, modification, and transport of cellular materials. Endoplasmic Reticulum Associated Protein Degradation (ERAD) is a cellular process that identifies unneeded or misfolded proteins of the endoplasmic reticulum and modifies the protein by attaching to it a ubiquitin protein. This ubiquitination process serves to mark the protein for destruction – a key process that helps prevent a range of diseases. Autocrine motility factor receptor (AMFR) is a transmembrane protein expressed on the cell surface and in a smooth subdomain of the endoplasmic reticulum (SER). AMFR has a critical function in the ubiquitination process, binding to the regulatory protein autocrine motility factor (AMF). Overexpression of AMF and AMFR occurs in a number of malignancies and participates in cancer cell migration during cancer progression and metastasis. It has been observed that AMF is secreted by tumour cells and acts as a protein messenger to other cells. However, its mechanisms remain unknown. Maria Abramow-Newerly is determining the signalling pathways used by AFMR following its binding to AMF, working to identify critical proteins and factors that may all tightly regulate AMFR expression and distribution within normal and cancer cell lines. In particular, she is focusing on characterizing AMFR as a G-protein coupled receptor, a family of proteins that serve as important drug targets for a number of diseases. Abramow-Newerly’s studies may contribute to the future design of drugs that specifically target components in the AMFR-signalling pathway to reduce cancer cell migration and metastasis
Formation, stabilization, and dynamic modulation of GABAergic inhibitory synapses in the central nervous system
In the central nervous system (CNS), the chemical synapse is the major site of communication between neurons (nerve cells). There are two main types of synapses in the CNS: excitatory glutamate synapses and inhibitory gamma-aminobutyric acid (GABA) synapses. Dysfunction of GABA synapses has been identified in disorders such as autism, schizophrenia, and depression. GABA synapses are also the main targets for drugs to treat epilepsy and anxiety. The protein neuroligin is a molecule that directs a neuron to form a synapse at the place where it comes in contact with another neuron. A specific type of neuroligin, Neuroligin-2, builds GABA synapses. However, little is known about why and how Neuroligin-2 is specific for building GABA synapses. Frederick Dobie was previously funded by MSFHR for his research in protein transport in neurons. He is now studying proteins involved in synaptogenesis (the process of building a synapse). To better understand how GABA synapses are formed, he is looking at regions of Neuroligin-2 that are important for this function. He is also studying how GABA synapses can change over time, responding to the specific needs of the neuron to fit into a fully-functioning brain. He is watching the growth and maturation of synapses over a period of several days, observing in real-time the strikingly dynamic appearance, disappearance, and movement of synapses. By understanding the biology underlying GABA synapses, Dobie hopes his work will ultimately lead to the advancement of therapies for a wide range of debilitating developmental, neurological, and psychiatric disorders.
OGC as a link between mitochondrial function, aging and diabetes
Marco Gallo is using Caenorhabditis elegans (a small worm) as a model organism to determine how mitochondrial 2-oxoglutarate carrier (OGC) affects aging and insulin signalling. He is studying how this protein interacts with the insulin pathway, and how it affects the development and function of mitochondria, which serve as the cell’s energy source. The proposed mechanism by which OGC is involved in the occurrence of diabetes is by modulating insulin signalling (the cascade of molecular events that result in insulin production). A related version of this protein (B0432.4) is also found in C. elegans. In worms, suppression of this protein resulted in a 20 per cent increase in their average and maximum life-span & in changes in the levels of insulin secretion. Gallo’s research aims to identify the mechanisms that mediate the interaction between OGC and insulin signalling. He is addressing this question with work on C. elegans, mouse & human cell lines. This work could shed more light on the changes that occur in the mitochondria and lead to metabolic diseases, with an emphasis on diabetes.
Expiratory flow limitation, dynamic hyperinflation and respiratory muscle fatigue during exercise in men and women
The act of breathing is a complex physiological process involving the interaction of numerous respiratory muscles and a neural control network. These respiratory muscles are the only skeletal muscles in the body whose functioning is necessary to sustain human life, making their ability to resist fatigue very important. Despite this, research has shown that high intensity exercise can induce respiratory muscle fatigue. Given the life-sustaining role of the respiratory muscles, it is important to understand the mechanisms of fatigue, how it is best detected, and how the human body responds and adapts to fatigue. Also, research suggests that physiological and anatomical differences may make women more susceptible to respiratory muscle fatigue compared to men. However, there are no studies that have systematically examined sex-based differences in respiratory muscle fatigue, and the “normal” pulmonary response to exercise in women is not well understood. Jordan Guenette was previously funded by MSFHR for his early PhD work identifying the respiratory limitations women face as they age. Now, he is examining the mechanisms and consequences of respiratory muscle fatigue in men and women during whole body exercise. His study will determine if the smaller lungs and airways in women cause greater respiratory muscle fatigue compared to men. He will also investigate whether high levels of respiratory muscle work reduce blood flow to other parts of the body and are responsible for impairment of whole body exercise performance. Guenette’s project will address questions significant to both basic and clinical science, outlining how men and women differ with respect to the normal pulmonary physiology of exercise. His findings have the potential to influence exercise rehabilitation programs for a variety of patient populations, and exercise prescription to prevent disease in healthy individuals.
Metacognitive factors in smoking: causal effects of maladaptive appraisals of cravings, thought suppression and nicotine withdrawal on craving severity
Cigarette smoking is directly responsible for the deaths of more than 45,000 Canadians each year. Although the majority of current smokers want to quit, smoking cessation can be extremely difficult. Since smokers are more likely to lapse after experiencing intense, persistent and distressing cravings, identifying factors that influence the severity of smoking-related thoughts, images and impulses is critical for understanding and preventing cessation relapse. Recent theories on the role of metacognitive processes in psychopathology hold promise for increasing our understanding of this important health issue. Metacognition refers to how people think about and react to unwanted thoughts and impulses. In her Master’s level research, Elizabeth found that among individuals attempting to quit smoking, metacognition is associated with nicotine craving severity and smoking cessation difficulty. Specifically, smokers who viewed their cravings as more important to control and more personally meaningful experienced more frequent, distressing and persistent cravings and were more likely to relapse one month later. Elizabeth is now building on this research, investigating the causal factors that contribute to personally meaningful interpretations of cravings, in relation to the effects of acute nicotine withdrawal and efforts to control thoughts about smoking. The results of Elizabeth’s research will help build understanding of the psychological factors that increase the risk for smoking relapse. They may also lead to innovative clinical strategies focused on appraisals and responses to cravings.
Logic, intuition and delusions: dual stream processing biases in decision-making
Delusions, a key characteristic of schizophrenia, are fixed false beliefs that are firmly held despite convincing evidence to the contrary. An underlying mechanism that can account for this debilitating symptom remains elusive. “Dual-stream information processing” is a decision-making model that divides reasoning into two separate components: a fast, intuitive stream, and a slower, logical stream, similar to our understanding of decisions made by the “”heart”” or “”gut”” versus those made by the “”head””. For most decisions, intuition and logical reasoning converge onto the same conclusion. However, in instances where intuition and reason do not agree, there may be processing differences between healthy people and people with schizophrenia. Healthy people show a bias toward the logical stream, prompting them to more carefully examine the available evidence. In schizophrenia, individuals may not detect conflict between the two streams and may not have a bias toward the logical conclusion. This could enable their erroneous intuitive interpretations of events to endure unchallenged, leading to delusions. William Speechley is testing this hypothesis by studying how people make sense of conflicts between the intuitive and logical streams of reasoning. Healthy individuals and delusional schizophrenia patients will be given reasoning tasks and their brain activity will be recorded using functional magnetic resonance imaging (fMRI). He predicts that healthy controls and delusional schizophrenia patients will differ when the two streams of reasoning conflict, and that the patient group will not adequately recruit logical reasoning areas of the brain during conflict. He also expects that fMRI will indicate greater activity in areas relating to intuitive processing among schizophrenics. This research will make a significant contribution to our understanding of the cognitive basis for the formation and maintenance of delusions in schizophrenia, potentially leading to more effective treatment strategies.
Urban renewal, drug related disorder and displacement: implications for health and HIV risk behaviour among injection drug using populations
It is estimated that 269,000 Canadians have injected drugs in the past year; statistics reveal that almost 20 per cent of all newly-recorded HIV infections are associated with injection drug use. High risk behaviours associated with injection drug use have made injection drug user populations especially vulnerable to HIV infection. This is particularly evident in Vancouver’s Downtown Eastside, which has experienced an explosive HIV epidemic among local injection drug users. For several years, this neighbourhood has felt the effects of new developments squeezing out older, low-income housing. This ongoing revitalization of Canada’s poorest postal code will soon be coupled with the upcoming 2010 Olympics. It is also expected that targeted policy interventions will be initiated to reduce the appearance of public disorder, particularly open illicit drug scenes. The implications for current residents are significant. The coming years have the potential to bring a massive displacement of injection drug users out of the Downtown Eastside, away from where most of their health and social services are currently situated. Kora DeBeck is monitoring how public policy changes related to urban revitalization affect risky behaviours and health among injection drug users. She is analyzing data from established cohort studies, which currently follow more than 2,000 injection drug users. Not only will DeBeck’s work help local policy makers respond to changing health service needs within Vancouver, it will also inform other cities experiencing similar urban transitions.
Ambient air pollution, residential traffic noise, and cardiovascular disease in British Columbia
Cardiovascular disease is the leading cause of death worldwide and accounts for approximately one-third of deaths across BC and Canada. Growing evidence has shown that air pollution and residential traffic noise are associated with cardiovascular disease. Chronic exposure to air pollution may induce and accelerate atherosclerosis, and environmental noise pollution is associated with hypertension. Previous studies have not clarified the independent effects of noise exposure and the joint effects of both ambient air pollution and residential traffic noise on the risk of cardiovascular events. Wenqi Gan is investigating if British Columbians exposed to higher levels of air pollution and residential traffic noise have an increased risk of cardiovascular events such as heart attacks, and whether this effect is greater among older age groups and individuals with other existing health conditions. Using air quality monitoring data , calculated environmental noise levels, as well as cardiovascularhospitalization and death records in Metro Vancouver, his study will follow more than half a million residents aged 45-85 over five years. Advanced statistical methods will be used to analyze the relationship between air pollution and noise exposure levels and the risk of cardiovascular events. Gan’s study will help identify the impacts of multiple environmental exposures on the risk of cardiovascular events and will also provide important evidence to support environmental policy making about air pollution, urban design, and transportation planning.