The study of the cellular basis of antibody-mediated immunity in infection is an exciting, emerging field of research that has profound implications for our understanding of host-virus interactions, protective immunity and HIV vaccine design. Antibodies are proteins that are produced by plasma cells and bind to molecules on the surface of invading pathogens, flagging them for destruction. Research in the field of HIV/AIDS has shown that antibodies, which neutralize a broad range of HIV isolates in test tubes, also protect animals from HIV-like pathogens, such as simian immunodeficiency virus (SIV). Thus, there has been a concerted effort to design vaccines that elicit broadly neutralizing antibodies targeting HIV. HIV-infected people rarely produce protective antibodies against a broad range of viral variants; this is of great concern to those attempting to produce a vaccine. Currently, there is no way of isolating the blood plasma cells that produce and secrete antibodies against a particular molecule or pathogen (antigen).
Dr. Naveed Gulzar's research involves an innovative approach to identify single, live HIV-specific plasma cells whose secreted antibodies bind proteins associated with HIV. He is working with a multidisciplinary team to develop an immunobiosensor that will allow him to locate single cells that secrete HIV-specific antibodies from thousands of antibody-secreting cells from the blood of HIV-infected people, and to isolate them for subsequent analyses. His goal will be to characterize the antibody response against HIV envelope proteins, and see how these change during the course of infection. The genes encoding these antibodies will be analyzed and their features compared. The results may provide new insights into our understanding of the immune response against HIV infection.
Dr. Gulzar's team includes Dr. Jamie Scott and several different analytical chemistry, physics and engineering research groups at Simon Fraser University and the University of Victoria, along with Cangene, a Canadian industrial partner. They anticipate that by understanding the genetic and cellular features associated with antibodies that neutralize a broad range of viral variants, they will be able to better inform the design of an HIV vaccine that elicits broadly neutralizing antibodies.
Borderline personality disorder (BPD) is among the most complex, misunderstood, and stigmatized mental health problems. It is a serious psychiatric condition characterized by instability in relationships, emotions, identity, and behaviour that often induces intense emotional suffering and places affected individuals at high risk of suicide and self-injury. Approximately 10% of individuals affected by BPD die by suicide, 75% have attempted suicide, and 70-80% self-injure. BPD is also a significant concern for the public health-care system. Patients affected by BPD represent up to 20% of psychiatric inpatients and heavily utilize outpatient and hospital emergency services. In fact, the estimated costs to the health-care system per year for each BPD patient range from US$12,000–$30,000. Self-injury and other problems in BPD appear to be related to problems in the management of emotions, or emotion regulation problems.
Dr. Alexander Chapman’s research aims to better understand and treat BPD and related problems, such as self-injury and suicidal behaviour, by examining the role of emotions in BPD and self-injury. Research in his lab, the Personality and Emotion Research Laboratory, includes a variety of studies aimed at better understanding what causes and maintains BPD and self-injury, as well as studies designed to help us understand how to effectively treat BPD. He is also conducting studies on the risks and protective factors for self-injury.
Dr. Chapman’s short-term goal is to continue to develop his research on BPD in two key areas: (1) the role of emotion regulation in BPD and self-injury, and (2) effective treatments for BPD and NSSI. He has several grants for studies in these areas and hopes to expand this research over the next five years. In the long-term, Dr. Chapman would like to develop an interdisciplinary research, treatment, and education centre focused on BPD, self-injury, and related health problems. Such a centre would be unique in Canada and would have the potential to significantly improve our understanding and treatment of BPD as well as the education and training of junior researchers and professionals.
Organ transplantation is a life-saving procedure for many individuals. Unfortunately, the long-term success of this procedure is compromised by the rejection of the transplanted organ(s) by the recipient's immune system. T cells are specialized cells of the immune system that protect against infections but that recognize and damage transplanted organs. Understanding how T cell responses are controlled will help to develop new methods to increase the long-term and specific acceptance of transplanted organs.
Dr. Jonathan Choy's research is focused on understanding how T cell survival and persistence is regulated and how these processes contribute to organ transplant rejection. By understanding this, Dr. Choy intends to find new ways of controlling the immune response against transplanted organs. Preventing rejection will improve outcomes for the approximately 2,000 Canadians who receive solid organ transplants each year, as well as for the many Canadians who are already living with transplants.
Within cells, RNA molecules perform a number of critical functions. Many of these functions are related to protein synthesis – the manufacture of various substances, including enzymes, hormones, and antibodies, that are necessary for the proper functioning of an organism. RNA molecules regulate gene expression (activation) to control cell reproduction, parent-specific inheritance and cell differentiation. They also interact with certain viruses during the establishment of viral infection. Despite recent advances in studying the dynamic interactions of proteins in living cells, where and when RNA molecules move through the cell to perform these various functions is still poorly understood. Elena Dogosheina is developing a new method to track RNA molecules in living cells as they move in and out of cell compartments. This movement will be visualized with the use of a fluorescent dye that contains microscopic magnetic beads to which RNA molecules will bind. This RNA tracking method could prove useful as a real time reporter for changes in RNA expression over space and time, and can be applied to study RNA splicing disorders and cancers involving differential expression of small RNAs. This method could also be used to study viral pathogenesis by visualizing intracellular organization and intercellular movement of viral nucleic acids in the course of infection.
The collagens are a family of more than 20 different proteins, all sharing the same basic structure. Collagen is the most abundant protein in mammals, comprising more than a quarter of the total protein in the human body. Its main role is in connective tissues, such as bone, cartilage, tendons and skin, where it is a vital structural element providing support and rigidity. Even small mutations can lead to weakened tissues, and genetic diseases such as brittle bone syndrome and osteoarthritis. Understanding the mechanical properties of collagen at the molecular level is important for understanding its role in these tissues, their formation, and their degeneration. In humans it has been found that the melting temperature of collagen – the temperature at which the molecule unwinds and separates – is very close to body temperature. The melting temperatures of various types of collagen have been found to be closely linked to the body temperature of the species in which they are present. This indicates that the thermal stability of collagen may be of great relevance to the structural role it plays. Benjamin Downing is investigating how temperature affects the collagen molecule’s strength and flexibility. He is using optical tweezers – a device that employs a tightly focused laser beam to manipulate micron-sized objects – to stretch the molecule and measure its stiffness and elasticity over a range of temperatures. This will reveal how closely the mechanical and thermal stabilities of the molecule are correlated. Downing’s research will help shed light on how the structure of a molecule gives it a particular strength and flexibility, knowledge that may be useful in the future design of artificial molecules that have specific properties. This information could be relevant in the development of biomaterials with applications in tissue repair.
The innate immune system is the body’s first line of defense to protect us from disease-causing microbes in our environment. However, the innate immune system can also generate other unintended and serious effects such as prolonged – and sometimes fatal – inflammation. The study of human systems such as the innate immune system is assisted by examining similar systems in other organisms, known as model organisms. Researchers link equivalent genes in the model organism to human genes, so that knowledge can be transferred from the model organism to humans. However, identifying equivalent genes between species can be a difficult task. The Brinkman laboratory at Simon Fraser University has developed a software program called Ortholuge that can detect pairs of genes that are likely to be “orthologs” – genes in different species that are similar to each other because they originated from a common ancestor. Orthologs are of significant interest when inferring function in humans based on different species, or when linking equivalent genes between species for large scale comparative analyses. Matthew Whiteside is working to improve the accuracy and speed of Ortholuge, adding functionality to the program that will resolve some of the more complex gene relationships. He will then use the software to perform a large-scale study of the innate immune system in humans, mice and animals important in agriculture, such as cattle. Whiteside’s work will be the first large-scale cross-species comparative analysis of the innate immune system. He hopes that this study will provide fundamental new insights regarding the evolution of innate immune system. This analysis may also highlight important innate immunity genes that are conserved between the species, with potential for identifying new therapeutic targets for immune diseases.
Violence, victimization, and suicide-related behaviours have many negative consequences on society and are viewed as critical public health issues. It is estimated that 2,000,000 violent crimes are committed each year in Canada, and that costs to victims, such as health services, approximate $47 billion annually (Statistics Canada, 2003). In addition to the important costs to the healthcare system, these violent outcomes greatly affect individuals’ quality of life as well as mental and physical health. Melissa Hendry’s research aims to reduce the risk of these negative behaviours by investigating risk factors for such behaviours; specifically, she is interested in hostile attributions, which is the attribution of malevolent intent to others, which she will study in a sample of civil psychiatric patients and criminal offenders. This research will assess participants’ level of hostile attributions using a new measure of hostile attributions, as well as other variables such as psychiatric symptoms, substance use, and criminal attitudes, to see how these relate to one another. Another purpose of her project is to look at the association between hostile attributions and behaviours such as violence, victimization, self-harm, and suicidal ideation and attempts. Exploring this research area to a greater degree could have far-reaching consequences in terms of decreasing the incidence of violence-related adverse outcomes in civil psychiatric patients and criminal offenders, thereby enhancing overall population health and reducing health care system costs. The results of Melissa’s research are expected to raise implications for reducing the risk of harmful behaviours in these individuals in terms of implementing new treatment and intervention programs.
Borderline Personality Disorder (BPD) is a psychiatric condition marked by instability in interpersonal relationships, behaviour, mood and self-image. BPD is associated with high rates of suicide, self-harm, substance abuse and hospitalization, and comes at a significant cost to both individuals and society. One symptom of BPD is an inability to maintain a stable sense of identity, which is associated with distress and health risk behaviours. However, the specific types of identity problems, the factors that contribute to identity problems, and the effects of identity disturbance in BPD are unclear. In recent decades, it has been proposed that personal identity is related to life narratives, where a cohesive life story helps a person to maintain a stable sense of identity. Nathalie Lovasz is clarifying the specific identity problems experienced by persons with BPD. Using measures of identity disturbance, she is comparing people with and without BPD. She is also examining potential contributors to identity disturbance in BPD, focusing in particular on whether narrative coherence mediates or accounts for identity disturbance, and the relationship between identity disturbances and emotional states. This research could help clinicians zero in on the specific types of identity problems faced by people with BPD. This research could also lead to improved diagnosis, identifying components of the symptom that are most unique and important to BPD.
When they are functioning well, intimate relationships contribute to better health and increased longevity. A cornerstone of well-functioning relationships is the ability to forgive a partner for relationship transgressions, such as telling lies, flirting with another person, or saying hurtful things. Repairing a relationship following the hurtful actions of one partner has consequences, not only for relationship quality, but also for physical health. One way that the act of forgiveness may be associated with health relates to cortisol production. Cortisol is a hormone released by the adrenal gland during times of stress. Chronic elevations of cortisol have negative effects on cardiovascular, immune, and brain systems and potentially increase the risk for diabetes, hypertension, immune system deficiency, and other illnesses. Being unforgiving has been shown to produce cortisol in a similar pattern to that which is experienced during other stress responses. Kim Watt is examining whether cortisol production is a mechanism for the link between forgiveness and general physical health. She is conducting her study with 200 newlywed couples, recording their physical health and measuring their cortisol levels at baseline and following a set of emotionally stressful marital discussions. Results from this study will contribute to a clearer understanding of the risk pathways by which negative relationship processes may lead to poor physical health. This may suggest that a focus on strengthening close relationships by improving couples’ skills when discussing relationship issues is a way of ultimately reducing health problems.
Dementia special care units (SCU) and freestanding special care facilities (SCF) for people with dementia are built using design principles that have been shown to enhance quality of life and reduce responsive behaviours that often occur when residents are disoriented or overstimulated by their surroundings. More supportive environments in these facilities are created through smaller unit sizes, homelike ambience, increased wayfinding, smaller activity spaces, and access to safe and secure wandering paths. Architectural planning and design features can improve the physical context where programmed activities such as music therapy, exercise sessions, creative arts, and therapy gardening occur. However, these specially designed spaces offer few therapeutic benefits without appropriate staff resources and family involvement to make the programs succeed, and consideration must be given to the combined effects of physical design, programs and policies, and staffing issues. Few studies have systematically assessed how modifications to the physical environment work in concert with social and organizational factors to enhance opportunities for residents to engage in positive social interactions through meaningful programmed activities. Krista Frazee is exploring the impact of the physical and social environments of care settings on residents’ social engagement during programmed activities in SCUs and SCFs, versus traditional integrated care facilities. She will also assess staff and family caregiver perceptions of activity spaces in helping them provide meaningful planned activities for residents. The findings from this study will be used to inform architects, interior designers, facility administrators and staff in various ways they can support the care and quality of life of residents with dementia through the integration of physical design and programmed activities.
