The bacteria Enteropathogenic E. coli (EPEC) is a major cause of infantile diarrhea, killing an estimated 100,000 children every year. (The bacteria is also closely related to enterohemorrhagic E. coli 0157:H7, which causes hamburger disease.) Most bacteria attach to existing proteins on host cells to cause disease. EPEC inserts its own protein into host cells and then attaches itself to the protein. Annick Gauthier is studying a specialized transport system—called a type III secretion system—that is believed to deliver this necessary protein from the EPEC bacteria into host cells. Her goal is to understand this fundamental mechanism, which is found only in disease-causing bacteria. Learning how this system works could provide targets for both vaccine and antibiotic development that would harm only the disease causing E. coli, and not the healthy bacteria that normally reside in the intestine.
Program: Trainee
The functional role of T-type calcium channels in cellular transformation and toxicity
Proteins called calcium channels regulate how calcium gets into nerve cells. In nerve cells, 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 central nervous system. When too much calcium enters these cells through calcium channels, a number of disorders can result, including congenital migraine, angina, epilepsy, hypertension and stroke. Michael Hildebrand is studying calcium channels called T-type channels, responsible for neuron firing, the nervous impulses that occur throughout the nervous system. Michael is investigating the structure and function of these channels to determine how they activate or inhibit calcium. He is also investigating drugs that can block specific channels to develop new treatments for epilepsy and various cardiovascular diseases.
Bioinformatic and functional analysis of retroelements involved in the regulation of human genes
Josette-Renée Landry is bringing both computer science and traditional molecular biology techniques to her research into the function of repetitive DNA sequences in the human genome (full collection of human genes). The Human Genome Project, completed in February 2001, revealed that more than 40 per cent of the human genome consists of repetitive sequences whose function remains largely unknown. Studies have suggested that some of these repeats, called retroelements, can influence how genes are expressed (turned on and off). Josette-Renée is working to further understanding of the function of retroelements by searching for repeats that appear to be involved in regulation of human genes. She will then use laboratory techniques to determine how these elements are involved in gene expression. Her work could lead to the discovery of important new gene regulatory factors. Since many genetic disorders result from aberrant gene regulation, the identification of retroelements that play a role in normal gene expression may provide insight into how regulatory mechanisms are altered in diseases such as cancer.
The roles of valvular myofibroblasts and endothelium in the development of human cardiac valvular disease
Vascular disease is the largest single cause of death in developed nations, and the incidence of cardiac valvular disease (disease in heart valves) is significant. The first cells to be adversely affected in vascular disease are endothelial cells, located on the inner lining of blood vessels. In the initial stages of vascular disease, there are modifications to the way endothelial cells regulate calcium signaling, an essential part of communication between cells. Willmann Liang is studying normal and abnormal calcium regulation in two types of heart valve cells: endothelial cells and myofibroblasts (cells involved in wound healing). Willmann aims to understand how calcium regulation in the human cardiac valve is altered with disease, and to determine how gene expressions governing the various components of calcium signaling are modified. Ultimately, the research may lead to the early prevention and treatment of valvular diseases.
Identification of components necessary for proper chromatid cohesion by global expression profiling
The error-free duplication of a multicelled organism’s genetic material is critical to its survival. Even small changes in the genetic code during duplication can lead to diseases such as cancer. Equally important to cell division is the error-free transmission of chromosomes to each of the two daughter cells, which depends on the proper regulation of sister chromatid cohesion (the attachment of both strands of newly-replicated DNA to the area of the chromosome called the centromere). When the mechanisms involved in chromatid cohesion are defective, there may be uneven segregation of chromosomes to daughter cells. This results in abnormal chromosome numbers (aneuploidy), a characteristic of many cancers. Ben Montpetit is studying the components responsible for regulating cohesion of sister chromatids. Ben’s research is aimed at providing a better understanding of what happens when the cohesion process is flawed, and to help identify therapeutic targets in cells with defects due to altered chromatid cohesion.
Identification of new targets for the treatment of androgen-independent Prostate Cancer
Current treatments for advanced prostate cancer eliminate the growth-promoting effects of androgens such as testosterone. Unfortunately, while this treatment is initially effective in reducing prostate growth, the usual outcome is an untreatable form of prostate cancer where the cancer becomes androgen-independent (grows without androgens). Steven Quayle is working to isolate the different genes that are expressed (activated) at different hormonal stages of prostate cancer. He is using a technique where prostate cancer cells grown in hollow fibres progress to androgen-independence in a controlled, reproducible manner. This will allow Steven to confirm the changes in gene expression that consistently occur with disease progression, and study in more detail the role of particular genes. These genes may be useful as indicators of disease progression, as well as potential targets for treatment.
The role of the tumor suppressor ING in cell growth and death in a frog model system
Mary Wagner is interested in the fundamental mechanisms that govern a cell’s decision to divide, mature or die. Armed with this information, she says, we can gain greater insight into many different diseases where these basic functions are altered. For example, cancer is characterized by uncontrolled cell division, and inappropriate cell death is the hallmark of degenerative diseases such as Alzheimer’s and muscular dystrophy. Mary is studying the role of ING (INhibitor of Growth), a protein that helps regulate these basic cell functions. While ING is also found in the cells of humans, mice, rats and yeast, Mary is studying the protein’s role in the metamorphosis of tadpoles into frogs—a drastic and rapid transformation involving tail death, leg growth and brain remodeling. She is also investigating how environmental pollutants can act as hormones to disrupt normal cell development and function.
Structural characterization of bacterial type III secretion system components
Bacterial resistance to antibiotics is on the rise and poses increasing threats to susceptible individuals, including the elderly, children and immunocompromised patients. To develop new and effective therapeutics against these microbial enemies, a thorough understanding of their pathogenic (disease-causing) mechanisms is required. Calvin Yip’s research focuses on characterizing the structural components of the bacterial type III secretion system (TTSS). Found in many pathogenic bacteria-including Enteropathogenic E. coli and Salmonella strains-these secretion devices are essential to the bacteria’s ability to cause disease. These systems allow pathogenic bacteria to deliver effector molecules into human cells, where they disrupt normal cellular function. Calvin is investigating how the TTSS structures are assembled and how they deliver effector molecules into cells. In conjunction with other biophysical studies, this work will result in a deeper understanding of the assembly and function of TTSS and may provide the basis to design new drugs.
Psychosocial predicators of success following memory intervention in older adults
Memory difficulties accompany the aging process. Two common examples include reduced ability to recall recent information or events and problems remembering to do something in the future. Programs have been developed to help older adults, including people with Alzheimer’s and their caregivers, deal with age-related memory changes. Although most benefit from these programs, not everyone responds equally and some do not seem to benefit at all. Little research has been done to investigate how psychosocial factors, such as personality characteristics, coping abilities and emotional status, affect the success of memory intervention programs. In her doctoral research, Patricia Lynn Ebert is assessing the impact of psychosocial factors on adults 70 and older who are in memory programs. Patricia hopes the results will lead to greater understanding of memory function in older adults, improved memory intervention programs, and better outcomes for program participants.
Mediators and moderators of the effective (and ineffective) healthcare provider-patient therapeutic relationship
Research has shown that a positive relationship between patients and their health care providers has a significant impact on the success of medical, psychological and drug treatments. The therapeutic relationship has a positive impact on both psychological and physiological factors, such as increasing hope and strengthening the immune system. In addition, the therapeutic relationship may have healing power in and of itself. Although the connection between the success of treatments and a therapeutic relationship has been established, little research has been done to identify the factors that contribute to an effective or ineffective relationship between a patient and health care provider. Robinder Bedi’s doctoral research will identify the factors that create a strong alliance. Health care professionals will be able to use this knowledge to establish more effective therapeutic relationships with patients, and to intervene early in situations where concerns about the relationship may impair treatment. Ultimately, this research should help improve patient outcomes and satisfaction with their care.