Neurons (nerve cells) need a regular supply of oxygen and nutrients to survive. When neurons are deprived of these essential factors for more than a few minutes, such as during a stroke or cardiac arrest, they undergo changes that lead to cell death. Intracellular concentrations of ions (e.g. sodium ions, calcium ions and protons) show dramatic changes during and following periods of anoxia or ischemia (oxygen deprivation). These changes play an important role in determining subsequent neuronal damage or death. Claire Sheldon is characterizing these anoxia-evoked changes in sodium ions, calcium ions and protons in hippocampal neurons and hopes to identify the mechanisms which contribute to their production. Her research focuses on the role(s) of intracellular pH regulating mechanisms to the changes observed, with particular emphasis on the Na+/H+ exchanger, an acid-extruding mechanism present in hippocampal neurons. Claire hopes her research will lead to new strategies to prevent or limit neuron death and the debilitating effects that stroke or cardiac arrest have on the central nervous system.
Research Location: University of British Columbia - Point Grey
Model Membrane studies of Amphotericin B's mechanism of action (towards less toxic AmB formulations and new tools for drug/membrane studies)
Amphotericin B (AmB) is an antifungal antibiotic used to treat infections in patients with depressed immune systems, such as cancer patients, organ donor recipients, diabetics and people with AIDS. Fungal infections are thought to account for up to 30 per cent of deaths among these patients. Although effective, use of AmB is limited because it can also cause kidney toxicity. AmB is known to interact with parts of the cell membrane, forming pores that allow leakage and ultimately cause cell death, but this process is poorly understood. Robin Stoodley is researching how the drug interacts with the body at the cellular and molecular levels, with the goal of finding ways to reformulate AmB to reduce its toxicity and improve effectiveness. The techniques Robin develops for this research may also be used to study chemotherapy and other drugs, leading to the development of better drug therapies.
Molecular mechanisms of SP12-mediated virulence in Salmonella Typhimurim
Salmonella enterica serovar Typhimurium is a bacterium that causes gastroenteritis, a type of food poisoning characterized by abdominal pain, fever, vomiting, and diarrhoea. Most Salmonella infections arise from oral ingestion of tainted food or water and are a significant cause of disease and death in animals and humans worldwide. Dr. Brian Coombes is studying the molecular mechanisms by which Salmonella use virulence factors to modify their host environment. Once injected into mammalian host cells, these virulence factors rearrange and reprogram the cells so that Salmonella can replicate and evade the body’s immune system. Learning more about how bacteria use specific virulence factors to manipulate their environment during infection may lead to the design of new therapeutic strategies to treat or block the disease process.
Mechanisms of pathogenic E. coli – host cell interactions
Escherichia coli (E. coli) bacteria cause numerous diseases including meningitis, urinary tract infections and diarrhea. Worldwide, enteropathogenic E. coli (EPEC) is one of the leading causes of diarrhea in children and is an endemic health threat in the developing world, causing the death of several hundred thousand people each year. Isolated outbreaks of enterohaemorrhagic E. coli (EHEC) also occur in developed countries, often transmitted in contaminated hamburgers and water supplies, and can cause diarrhea and fatal kidney disease. After binding to the cells that line the intestine, E. coli injects several proteins that lead to diarrhea and disease. Dr. Philip Hardwidge aims to identify these proteins and determine their structure and function. He is also examining how intestinal cells respond to E. coli at the level of gene expression, using an advanced technique to analyze several thousand genes at a time. This research could guide the design of future vaccines and antibiotics to prevent and treat E. coli.
Synaesthesia: A window into abnormal perceptual experiences
Synaesthesia is a fascinating condition in which individuals can experience tactile sensations when they taste foods or perceive colours when they hear sounds. Very little is known about the brain activity underlying this condition. Although synaesthesia occurs in healthy people, synaesthetic experiences are reminiscent of the abnormal perceptions that occur in other disorders such as schizophrenia. Dr. Daniel Smilek is using neuroimaging techniques to investigate the brain activity associated with this condition. Results from the research could provide insight into the brain processes involved with abnormal perception in various syndromes, such as schizophrenia, as well as the processes underlying perception in normal individuals.
The contribution of amyloid-induced neuroinflammatory factors to disturbances in neural processes related to learning and memory
Close to 250,000 Canadians over the age of 65 have Alzheimer’s disease. The leading cause of dementia, Alzheimer’s is a degenerative disease characterized by loss of memory, judgement and reasoning, and changes in mood and behaviour. There is no known cause or cure. Within the brain, cells shrink or disappear and are replaced by dense spots, or plaques, which contain a protein called beta amyloid. Recent studies show chronic inflammation in the brain cells plays an important role in the development of Alzheimer Disease. Microglia — the smallest cells surrounding neurons — seem to contribute to this process, and the beta amyloid protein interacts with these cells. Dr. Aline Stephan is studying how amyloid deposits inside the brain induce neural changes to affect synaptic processes and memory function. Her research will help explain how inflammation exacerbates memory deficits, and may lead to new therapies to treat the disease.
Investigating protein expression and localization in microsporidian parasites during infection
Dr. Ross Waller’s earlier research into the malaria parasite has contributed important information leading to a new array of drugs to treat the disease. Now he is studying microsporidia, a group of intracellular parasites that infect humans and animals. In particular, microsporidia infect immune-compromised individuals, causing encephalitis (inflammation of the brain) and gastroenteritis (inflammation of the stomach and intestines). The parasites have a remarkable method for invading host cells. This small, simple spore releases a harpoon-like tube that pierces the host cell. The parasite contents are then injected into the host through this tube, establishing the infection. Ross is identifying specific genes and proteins involved in the infection process, using genome sequences that have identified all the genes in two microsporidia. He is looking at the way proteins are prepared prior to and during the initial stages of infection. The results may provide new ways to combat these organisms.
Analysis of specific host responses to pathogenic Escherichia coli infection
Escherichia coli (E. coli) bacteria cause much disease and death worldwide. However, little is known about the mechanisms these bacteria and others use to cause disease in their hosts. Specific virulence factors – strategies and molecules that enable the bacteria to cause infection – are needed for disease to develop. The bacteria inject these virulence factors into host cells, which affect normal cellular processes. Dr. Mark Wickham is using two pathogens, E. coli and Citrobacter rodentium, as a model to research how pathogens produce disease at the molecular and cellular levels. Understanding how this process occurs will address a gap in current knowledge, thus improving health and health services, and the research results could be applicable to other disease-causing organisms.
Role of culture, rumination, and anger suppression on stress recovery
Researchers have identified several factors, including chronic hostility and a tendency to suppress emotion, that may predispose people to stress-related illnesses such as gastrointestinal problems and cardiovascular disease. A compounding factor is that cultures differ in the degree to which they expect members to show or suppress emotion, such as anger; yet little is known about the impact of culturally-mandated suppression of emotion on stress-related illnesses. Jeremy Anderson is examining how cultural and psychological factors may contribute to stress-related illnesses. His study involves provoking anger from two culturally distinct groups of participants, allowing just one of the groups to express the anger, and then comparing the stress responses from the groups by measuring blood pressure, heart rate and the stress hormone cortisol. The research will improve understanding of how culture affects stress-related illnesses and may also help in the design and targeting of healthy interventions for specific groups.
Trauma, dissociation and post traumatic stress disorder (PTSD) in violent offenders: The cycle of violence revisited
Research indicates that many violent crime offenders have been victims of violent crime. Many develop stress-related psychiatric disorders, such as Posttraumatic Stress Disorder, as a response to perpetrating or being victimized by violent crime. Barry Cooper’s earlier research focused on the development of Posttraumatic Stress Disorder symptoms and their effect on memory in victims of violent crimes. Now he is examining the complex factors that contribute to the development, severity, and maintenance of the condition in violent crime offenders. His research involves interviewing violent crime offenders incarcerated in BC and developing an extensive database detailing factors such as their personality characteristics, history of trauma, severity and type of violence, use of alcohol or other substances, and memories of their crimes and traumatic experiences. The results will help refine assessment techniques and treatment programs for violent offenders, leading to improved rehabilitation and a lower rate of violent offences.