Modelling and simulating intra-cellular signalling systems in response to pathogen invasions by semantic networks

Organisms that cause disease use various strategies to create infection. Bacteria such as Mycobacterium tuberculosis invade cells in the human immune system. These bacteria manipulate the internal machinery of a host cell to enter and survive inside the cell. A cell contains many different types of molecules that interact in complex ways to control cell behaviours. Michael Hsing is studying these interactions to understand how bacterial invasions occur. He is using a computer method, called the semantic network, to simulate molecular interactions and cellular behaviours during bacterial invasions. The research could enable researchers to predict how cells respond in different situations, potentially leading to development of drugs to prevent and treat bacterial infections.

Impact of labour market change on community and workplace health in health services

A growing body of evidence indicates that a lack of control over working conditions contributes significantly to poor health and that social networks have a positive impact on health. Amber Louie is building on that research by analyzing the impact of organizational restructuring and changing work conditions on health care workers. Amber is examining the barriers to workers’ control in the health care sector, and the factors that facilitate or serve as incentives for workers’ control. She is also investigating the relative effectiveness of the various forms that workers’ control may take. The research involves interviewing community health workers to assess individual perceptions about social support, participation in decision-making and other factors that affect their working conditions. The study could provide important information for health care practitioners, human resource managers and community developers to use in the design, implementation and evaluation of workplace and community health promotion programs.

Identification and characterization of genes dysregulated by YB-1 during prostate tumour progression

Prostate cancer is the second leading cause of cancer death in men. While curable if discovered early, many men are diagnosed after the disease has metastasized (spread) to other parts of the body. At this point few treatments are effective. Androgens (male sex hormones) regulate prostate growth and development. Removing androgens is the most effective treatment for advanced prostate cancer. However, some cancer cells eventually adapt and become androgen-independent, enabling the disease to progress. The YB-1 protein regulates two genes involved in the progression of androgen independence. Using sophisticated DNA microarray technology, Dr. Susan Moore aims to identify additional genes regulated by this protein to learn how androgen independence develops. The findings could lead to earlier diagnosis and new treatments for prostate cancer.

Computational identification of genetic variation in gene regulatory networks

Our genes encode all the information that makes us human. The recent sequencing of the human genome, completed in 2003, identified all of the approximately 30,000 genes in human DNA. However, each person has variations in their genetic makeup that account for the diversity in their quality of life. A major focus of genetic research is studying the nature of genetic variation. Single nucleotide polymorphisms (SNPs) are variations in DNA sequences that are the most common molecular mechanisms of genetic variation. Studies show SNPs play a role in the development of various diseases, including depression, cancer, lupus and Alzheimer’s. Stephen Montgomery, who was part of the research team at Canada’s Michael Smith Genome Sciences Centre that sequenced the SARS virus, has been designing and building software to aid in identifying SNPs and other sources of genetic variation that regulate gene expression (the process by which genes are transcribed and translated into proteins). His work on further developing these tools and techniques could improve understanding of the molecular causes of genetic variation, which could suggest new therapies for combating diseases.

Patterns of social anxiety in Chinese and European Canadian populations

Many people experience the social anxiety of being uncomfortable in certain social situations. But social anxiety can develop into social phobia, a clinical condition characterized by excessive fear related to attention and scrutiny by others that can significantly impair quality of life. Surveys in Asia have shown Asians experience considerably less social phobia than Western populations. But North American studies show Asians report higher levels of social anxiety than Caucasians. Lorena Hsu is examining two possible explanations for this discrepancy: Asians are less impaired by social anxiety and therefore less likely to develop social phobia, or Asians are less likely to openly admit to symptoms of social phobia. Using data collected from questionnaires and interviews of Chinese and European Canadians, Lorena will determine which explanation provides a better account of the discrepancy. This study could help explain how people in different cultures experience and express social anxiety, and contribute to development of culturally appropriate mental health services.

A novel approach to studying DNA copy number variation in schizophrenia and bipolar disorder

Schizophrenia and bipolar disease are severe mental illnesses that affect thinking, mood and behaviour, and cause lifelong disability. Schizophrenia alone costs the Canadian economy about $2.5 billion per year. While the exact causes remain unknown, both disorders are thought to arise from the interaction of genetic defects with environmental factors. Research into these psychotic disorders lags behind advances in other health fields, so new and innovative research strategies are needed. Studies have shown that certain DNA changes can strongly predispose people to psychotic disorders, but the full scope of DNA changes in schizophrenia and bipolar disease has not been explored. Dr. Robert Holt is using new technology called microarray comparative genome hybridization to scan the entire genome of patients with schizophrenia and bipolar disease to detect losses or gains of DNA. The research could contribute to better understanding of the genetic factors that predispose people to schizophrenia and bipolar disorder, lead to diagnostic tests to identify those at risk, and strategies for early intervention to achieve better outcomes.

Genetic Pathology Evaluation Centre

Researchers at the centre are using tissue microarray technology to systematically validate whether certain biomarkers – cellular or molecular substances found in cancers – can be used to improve cancer diagnostics or predict the course of disease. With the ability to test hundreds of tumour samples at a time, researchers can assess the potential value of potential biomarkers with an efficiency that would have been unimaginable just a few years ago.

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HIV, STIs and massage parlour workers: application of social network analysis and mathematical modeling to assess the potential for disease propagation

Studies on the spread of sexually transmitted infections (STIs) and HIV usually focus on individual risk factors such as the number of partners and condom use. But these factors do not fully explain epidemics. Social Network Analysis, a new approach, looks at how relationships between people in defined groups affect risk of disease spread. Valencia Remple is using this approach to conduct a sexual health survey of women who work in massage parlours. As part of the study, trained peer outreach workers are conducting in-depth interviews with workers to obtain information about their sexual behaviour, histories of STIs and the characteristics of their sexual partners. She is also measuring factors known to influence the spread of STIs, such as bridging. Bridging occurs when people in one defined group have sexual contact with members of different groups, which could introduce infections into previously uninfected populations. The results of this research could be used to develop targeted health services for this vulnerable and hidden population.

GLP-1 gene therapy for Diabetes

Diabetes is a chronic disease that affects more than two million Canadians and 135 million people worldwide. People with this condition are unable to maintain normal blood sugar levels due to a lack of, or insensitivity to, insulin, a hormone that regulates blood sugar levels. Current treatments include insulin injections or oral drugs that stimulate insulin release or improve insulin sensitivity; however, daily administration is required due to their short-term effects. Gene therapy represents an exciting approach in treating diabetes by providing a means to achieve automatic delivery of therapeutic hormones within the body. Glucagon-like peptide-1 (GLP-1) is an intestinal gut hormone with a variety of anti-diabetic effects. Initial clinical studies show that GLP-1 can stimulate insulin production and release. Corinna Lee is examining whether gene therapy could achieve automatic, long-term release of GLP-1 from cells within the body. This research could provide insights into a new method of diabetes treatment that could eliminate the need for daily injections or oral drugs.

Mechanism of myocardial dysfunction in sepsis

More people die each year from sepsis, a severe, overwhelming infection and inflammation, than from breast or colon cancer. The infection is also 20 times more deadly than a heart attack. Septic shock (severe sepsis) causes multiple organ failure and is the leading cause of death in North American intensive care units. Sepsis impairs the heart’s ability to use oxygen, which is necessary for the heart to pump normally. Dr. Ryon Bateman is investigating whether damage to capillaries (the smallest blood vessels) prevents oxygen from being delivered within the heart or whether dysfunction of the mitochondria (the parts of the cell that consume oxygen) prevents oxygen from being used by the heart. Dr. Bateman is using advanced microscopic imaging techniques to generate three-dimensional images of heart capillaries to look for changes in their number and spacing. He is also assessing whether regions of the heart with low oxygen have tissue damage, and if mitochondria are damaged in these regions. The research could explain why the heart is damaged during sepsis, leading to new treatments for critically ill septic patients.