Recent data suggest that 1.5 million Canadians, or 12 per cent of the population, will experience an episode of major depression at some point in their lives. For many, depression often becomes a chronic illness, with recurrent episodes. Cognitive neuroscience researchers are currently examining networks in the brain that are involved in depression, in the hope of developing better treatments and therapies for this devastating disease. MSFHR previously funded Fern Jaspers-Fayer for her Master’s research on the electrical brain activity changes associated with Seasonal Affective Disorder (SAD). For her PhD work, Jaspers-Fayer is continuing her studies in this area. She has studied the timing and location of electrical brain signals from electroencephalograms (EEGs) that were recorded from people with symptoms of depression while they completed a number of cognitive tests. She found that although everyone pays more attention to negative events than positive ones, people with low mood will go on to ruminate about these events. This contemplation, which may become persistent and brooding, then affects how they behave. Using new techniques to localize these effects in the brain, Jaspers-Fayer is now disentangling both when and where in the brain the process of rumination begins and what conditions increase the likelihood and the duration of rumination. Jaspers-Fayer’s work will ultimately lend knowledge to our understanding of the underlying cognitive mechanisms involved in emotion, helping to pinpoint the timing and activation of brain areas involved in depression. Her research in rumination could potentially inform new approaches and therapies for treating depression.
Research Location: Simon Fraser University
Spatial epidemiology of trauma: understanding and preventing injury through geographic analysis
Over the course of the last two decades, the notion that health and well-being is tied to societal and environmental circumstances that may overlap and intersect with important elements of individual experiences has been widely utilized as a means of characterizing the inequitable distribution of a wide range of health outcomes, including injuries. Importantly, the population health perspective model is transforming how we understand the complex interaction between the environment and injuries, and tailoring prevention and policy responses to address the inequitable distribution of their occurrence. Yet, there are currently no frameworks in place for how we quantify the interconnectivity between social, environmental, and geographical determinants of injury and building evidence that highlights the underlying relationship between all three factors with injuries. Addressing the ecological and geographical questions regarding this complex interaction entails integrating the current injury prevention models with the tools and analysis functions of geographic information systems (GIS). GIS are widely recognized as essential tools in public health promotion and surveillance as they allow for the integration of multiple data sources and the visual and spatial analysis of health data in relation to locations, distances, or proximities. GIS can increase our understanding of current population access to emergency medical services, the extent that injuries ‘cluster’ in certain areas and among certain population groups, as well as help researchers better understand and locate the links between people and their environments that may either reduce or increase injury risk. Nathaniel is currently applying GIS in a number of research areas in order to determine where important systems elements might be augmented to improve population access to critical care, for identifying incidence patterns that might have gone under noticed had they not been examined using GIS, as well as how this technology might be used to help researchers more accurately target prevention efforts to reach communities in-need. This research will help structure ongoing injury prevention efforts in British Columbia as well as provide future researchers with a number of frameworks for using GIS to improve our understanding of the societal, environmental, and geographic factors associated with injury.
Early mother-infant interaction and infant mental health
The quality of the mother-infant relationship early in infancy forms a foundation for infants’ subsequent social and emotional development. In particular, mothers’ sensitive responses to behavioural and emotional cues help their infants develop a sense of self and help them regulate their emotions. Attachment — or the bond between infants and their caregivers — is a developmental achievement in the first year of life that is essential for healthy physical and psychological growth. Studies have shown that insecurely-attached infants are at risk for a range of negative developmental outcomes. Nancy Mcquaid was funded by MSFHR for her early PhD work into the relationship between attachment and infant mental health. She is continuing this longitudinal investigation among a community sample of mothers and their infants. Mcquaid’s research is now evaluating whether maternal responsiveness and infant social expectations observed at four months are related to subsequent infant mental health at 12 and 30 months of age. She is also assessing the impact of mother and infant temperament to healthy developmental outcomes. Mcquaid’s research will contribute to our understanding of healthy infant development and will help develop means of intervention for infants who are at risk for developmental emotional and interactive disturbances, such as infants of mothers with postpartum depression and low birth weight infants.
Health Innovation Design and Evaluation Research Team
In their ongoing efforts to improve health outcomes, decrease health care costs, and increase administrative efficiency, health care agencies are increasingly investing in information-based technologies (IT). Recently, the Canadian government highlighted the need for developing new methods for evaluating new health sector technologies in order to provide insight into the challenges associated with increased use of IT in health care settings. This award supports the development of a team that is researching the use of IT for epidemiological data collection (EDC), also known as e-epidemiology. The team’s goals include: identifying technological, organizational, governance and implementation challenges associated with the increased use of IT for EDC; addressing data quality issues arising from increased use of IT for EDC; and improving collaborations among researchers, decision makers and technology developers across disciplines who share an interest in e-epidemiology. The team hopes to improve the quality of evidence used in decision making about information technologies used for collecting epidemiological data in BC.
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
Multimodal Imaging Instrumentation for Non-Invasive Functional Retinal Imaging
With an aging population comes an increase in a number of diseases and conditions of the eye. A recent advance in imaging – called optical coherence tomography (OCT) – provides a non-invasive way to create high resolution, cross-sectional images of inside the eye. OCT is particularly useful in providing these images of the retina, showing cross sectional images of the various layers with resolution equivalent to a low-power microscope and better than other imaging techniques such as magnetic resonance imaging (MRI).
A new technological development called Fourier Domain (FD) OCT provides these images much more quickly than existing systems. It has also been successful in creating three-dimensional images of the retina, which were previously not possible to obtain. However, clinical use of FD OCT is limited as it generates only an image of the eye’s structures, without providing any functional information about the biological processes at play.
Dr. Marinko Sarunic’s research builds on earlier work where he successfully combined FD OCT imaging with molecular contrast capabilities to provide functional information. He is now using this technology to determine its usefulness in retinal diagnostics, the study of disease processes, and the testing of new drugs and therapies. Development of FD OCT imaging techniques will help physicians better understand and manage ophthalmic conditions, through high resolution visualization and improved minimally-invasive, image-guided procedures.
Total Synthesis and Structure-Activity Studies of a New Anti-Cancer Drug Based on the Natural Product, Imbricatine
With an estimated 159,900 new cancer cases and 72,200 deaths from cancer predicted to occur this year alone in Canada, the need for new cancer therapies with unique mechanisms of action is urgent. Researchers are finding a promising resource among the ocean’s estimated one to two million structurally diverse microbial species. Compounds derived from marine organisms offer great potential in the fight against cancer; in the past decade, more than 30 natural products from the ocean have entered preclinical and clinical trials as potential treatments for cancer. However, it is often not ecologically or economically feasible to extract the active ingredient by harvesting natural sources in the ocean. Synthetic organic chemistry – where molecules are engineered in the laboratory – serves as an alternative source of these compounds. Inhee Cho is focusing on the synthesis of imbricatine, a chemical originally isolated from the Pacific sea star that shows significant anti-tumour properties. The structural core of imbricatine includes tetrahydroisoquinoline, a molecular structure that is also found in many biologically active agents, including anti-tumour antibiotics and drugs that treat diseases such as asthma, Parkinson’s and other nervous system diseases. Cho is developing an efficient way to synthesize tetrahydroisoquinoine, allowing rapid access to this important class of natural products in order to obtain enough material for biological testing and chemotherapy. Cho’s work may facilitate the discovery of new lead compounds with useful pharmacological properties, potentially leading to new therapies for treating cancer
Trajectories towards self-harm, suicide, and other maladaptive coping behaviours
Borderline personality disorder is a serious mental health problem characterized by heightened emotional vulnerability and difficulty modulating emotional responses. Individuals with BPD have high rates of health risk behaviours, such as suicide attempts (75 per cent), self-harm (69-80 per cent), and substance abuse (60 per cent). Despite frequent intense emotional reactions to stressful events, people with BPD lack the skills to reduce their distress through adaptive coping methods. In an effort to reduce these unpleasant emotions and feel better, persons with BPD features often resort to maladaptive coping strategies that are quick and easy to execute (e.g., self-harm, substance abuse) but have negative long-term consequences. However, not everyone with BPD engages in these risky behaviours in response to every stressor, and the specific triggers for these behaviours are largely unknown. Certain types of emotional states (e.g., shame) and life stressors (e.g., being rejected) may be particularly linked with self-destructive coping behaviours. Kristy Walters is examining the specific negative emotions or particular stressful triggers that may be strongly associated with maladaptive behaviours such as self-harm, substance abuse, or suicide. This research will also examine whether or not these relationships among emotions, stressors, and maladaptive behaviours is unique among individuals with borderline personality disorder (BPD). A better understanding of which specific emotions constitute cause for concern, or which types of negative events are more likely to result in self-destructive behaviour, will considerably improve clinicians’ ability to evaluate their client’s level of risk and better identify those clients who are in urgent need of life-saving interventions.