Carrie Rosenberger’s research focuses on Salmonella, the bacteria responsible for an estimated 16 million cases of typhoid fever worldwide each year. Research has shown that Salmonella typhimurium, a strain of the bacteria, causes widespread disease by penetrating the inner membrane of the intestinal wall and residing in macrophages (immune cells that normally help destroy bacteria). Rosenberger is investigating how Salmonella typhimurium avoids destruction by altering macrophage genes. To study the complex interactions between cells and the bacteria, she is using gene arrays, technology that enables simultaneous measurement of how hundreds of macrophage genes change during infection. Rosenberger hopes the research will increase understanding of how Salmonella causes disease and helps in the design of more effective treatments. She also hopes to broaden knowledge of how cells and pathogens (disease-producing organisms) interact.
Research Pillar: Biomedical
Molecular Basis of Mammary Epithelial Cell Polarization
Aruna Somasiri has long been interested in how cells function at the molecular level. Somasiri believes understanding errors in cell regulation will provide the most valuable information in designing treatments for cancer. He’s contributing to that knowledge by investigating the process that causes benign cancer tumours to metastasize – travel from their original tissue and form secondary tumours that are difficult to eliminate. Research has revealed that certain disruptions to cellular activity influence this process. Somasiri aims to understand the normal process of differentiation – cells forming other cells – in breast cells. He hopes the research will reveal insights about how misregulation of the process can initiate breast cancer metastasis.
Prediction and prevention of autoimmune diabetes mellitus
Jacqueline Trudeau’s research focuses on autoimmune disease – disorders that cause the immune system to destroy normal body tissues. She’s specifically interested in how a specific type of immune cell, T-cells, are mistakenly activated in autoimmune disorders. Type 1 diabetes is an autoimmune disease in which T-cells destroy insulin-producing B-cells in the pancreas. This leads to hyperglycemia (high blood glucose), insulin dependence and other complications associated with diabetes. Given that autoimmune diseases may develop and be present for years before being diagnosed, they are difficult to treat. It is also challenging to understand how the disease process is initiated and the course of development thereafter. Jacqueline is developing techniques to identify T-cells that specifically destroy B-Cells before hyperglycemia sets in. She aims to design an approach for identifying children at the early stage of developing diabetes, a critical window of opportunity when treatment could save remaining B-cells
Pathogenesis and Treatment of Huntington's Disease
There is currently no effective treatment for Huntington’s disease, a progressive and ultimately fatal neurological disorder caused by a defect in the Huntington Disease gene. Symptoms of the inherited disease, which usually appear at mid-life, include abnormalities in movement, difficulties with awareness and judgement, and emotional instability. Using genetically altered mice, Jeremy Van Raamsdonk is investigating the underlying genetic and cellular changes that give rise to Huntington’s disease and potential treatment strategies. The research involves testing both drug and gene-based treatments targeted at the root cause of the disease, as well as assessing treatments to minimize the damage to the nervous system. By developing specific treatment strategies, Van Raamsdonk aims to limit damage to nervous system cells and increase the lifespan and quality of life for people with Huntington’s disease.
Regulation of inhibitory receptor gene expression by Natural Killer cells
Natural Killer (NK) cells play an important role in the immune system: targeting and destroying tumour and virus infected cells that evade other branches of the immune system. Brian Wilhelm is striving to understand what regulates the ability of NK cells to distinguish between abnormal cells and healthy cells. While it’s known that receptors on NK cells enable them to distinguish between cells, there is little knowledge about the genetic mechanisms that direct the process. He hopes that the research on receptor genes will provide insights about how individual genes and sets of genes specific to NK cells are regulated. As well, the work may shed light on the role of receptor genes in developing blood disorders and also about the use of NK cells in immune-based therapies.
Host Cell Signalling Following Coxsackievirus B3 Infection: Elucidation of Anti-Apoptotic Survival Mechanisms
Robert Yanagawa’s overall goal as a researcher is to increase our understanding of cardiovascular diseases. With that in mind Yanagawa is investigating Coxsackievirus B3, the primary cause of viral myocarditis (inflammation of the heart muscle), a condition that may result in chronic irregular heart beats, heart failure and sudden death. Organ transplantation is the only definitive treatment for heart failure caused by this virus. Yanagawa is examining the ability of host cells within infected cardiac muscle to activate protective signalling mechanisms. When stimulated, these mechanisms may maintain heart muscle viability, slow replication of the virus and preserve heart function. Yanagawa hopes that establishing new insights about protective mechanisms will ultimately lead to more effective treatments for viral myocarditis.
Lymphocyte defects in X-linked lymphoproliferative disease
Dr. Ala Aoukaty has spent nine years investigating anti-viral and anti-tumour cells. Aoukaty’s doctoral research focused on understanding the signalling process that occurs after receptors on the surface of cells are engaged. That experience provided him with a strong background to conduct postdoctoral research on X-linked lymphoproliferative disease (XLP), a fatal disorder caused by a genetic mutation and characterized by severe infectious mononucleosis, immune deficiency and malignant lymphomas (tumours). A large Aboriginal family that carries the genetic mutation has been identified. Aoukaty will isolate and study cells from XLP patients and carriers of the disease in the family to study the abnormal immune responses at work. The research will shed light on how the immune system specifically responds to Epstein-Barr virus, which causes infectious mononucleosis, provide insights in general about lymphoproliferative disorders (diseases of immune system tissue), and enable the testing of gene replacement therapies.
Role of Membrane Binding in Regulation of the Activators of Ras
Dr. Joanne Johnson’s research examines events at the molecular level that ultimately lead to cell growth. Among the events is activation of cell surface receptors by ligand molecules, which leads to generation of specialized lipids in the cell membrane. These lipids act as signals to promote membrane binding and activation of proteins. Johnson is assessing the role of Diacylglycerol (DAG), and two newly identified proteins, RasGRP and CalDAG1. Johnson is specifically investigating how DAG and other lipids influence membrane binding and activity of RasGRP and CalDAG1, which function to activate the Ras protein, a critical switch in the control of cell growth. Knowledge of this process may lead to development of specific inhibitor drugs controlling cell growth and defending against tumours.
The Contribution of Auditory Temporal Processing to Speech Perception in Noise: Speech Comprehension Deficits in the Elderly
A common and frustrating difficulty for the elderly is understanding speech in everyday conversation, especially where the background is noisy. People commonly report that different sound sources are “Jumbled” (e.g. voices, background sounds). We propose that the brain relies on high fidelity transmission of sound codes and compares their timing in order to sort out different sound sources: When auditory neurons are activated in synchrony, their activity is perceived as representing a single sound source. Conversely, asynchronous activation conveys the presence of multiple sources. We hypothesize that age-related changes in auditory neurons introduce timing errors to the sound code, thereby compromising the use of synchrony to separate multiple sounds during perception. We will simulate this age-related hearing disorder by altering the temporal structure of speech to disrupt neural synchrony and speech perception in noise so that younger listeners experience elderly-like difficulties understanding speech in noise. In parallel, we will simulate the disorder in established computer models of auditory neurons to delineate the influence of reduced signal fidelity on sound codes and synchrony binding in the brain. The long-term goal of this research is the development of a novel hearing test battery designed to address speech-in-noise problem. We also hope to contribute to the development of novel hearing aid technology, where the device employs the temporal structure of sound to separate a single voice from the noisy environment. Currently, hearing aid technology entails the indiscriminant amplification of all sounds in the listener’s environment.
Utilization of large-scale genomic yeast modifier screens in the identification of unique genes required for chromosome segregation
Chromosome segregation is a fundamentally important process for human cells. When cells divide, they normally ensure both daughter cells receive one copy of each chromosome. But defects in this process can cause cells to lose chromosomes or receive extra ones. Inaccurate chromosome segregation can lead to diseases such as cancer. Despite the importance of this process, researchers are just beginning to identify and understand the genes and molecular mechanisms involved. Dr. Kristin Baetz is investigating the genes and mechanisms needed to ensure accurate chromosome segregation. Baetz is developing a genomic screen to identify unique genes in a genetic yeast model, whose genome and cell biology are remarkably similar to that of humans. Building knowledge about chromosome instability could lead to new treatments for common forms of cancer.