Up to 23,000 preventable deaths are estimated to occur each year in Canadian hospitals. Nurses who provide care at the bedside are well positioned to promote patient safety, because a critical component of their role is to notice and gauge potential risks. Although research suggests that nursesâ workload, training and experience influence patient mortality, little is known about the actual processes that nurses use to prevent or reduce error. Kim Shearer is applying the model of âSituational Awarenessâ (SA) to study pediatric nurses performing resuscitation of children in hospital. SA â defined as knowing what is going on in your environment â has been proposed as the primary basis for decision-making and performance in complex, dynamic systems, helping researchers understand how threats within the environment are gauged and safety is facilitated. Kimâs study will identify factors that promote or impede nursesâ ability to gauge the work environment and make decisions, generating the basic knowledge needed to create computer simulations for teaching and testing SA in pediatric resuscitation. Findings of this research will help to prevent or minimize error and enable development of novel health education interventions to improve SA and hence the safety of children in dynamic and complex acute care environments.
Year: 2006
Quantitative Single Cell Proteomics for Stem Cell Analysis in Microfluidic Devices
Stem cells are defined by their unique capabilities to either replicate (self-renew) or differentiate into more specialized cell types such as nerve cells (neurons), immune cells and skin cells. If health researchers could controllably direct stem cells to differentiate into particular cell types, stem cells could potentially be used as clinical therapeutics for a diverse range of diseases, including neurodegenerative diseases, autoimmune disorders, heart and liver disease, and cancer. Presently, the control of stem cell differentiation is hampered because researchers lack the necessary knowledge and tools for studying the molecular pathways that guide stem cell differentiation into specific cell types. Anupam Singhalâs research seeks to harness recent advances in micron-sized fluid-handling devices and nanotechnology in order to quantitatively study stem cells at the single cell level. In particular, he will propose a general platform for performing rapid and high-throughput quantification of multiple proteins in single stem cells. This strategy should help to identify proteins (e.g. transcription factors for gene expression, secreted proteins) that influence the stem cell fate decision. This information will then be used to construct model molecular pathways that guide stem cell differentiation, a critical milestone that must be reached before stem cells will find widespread clinical applications.
Phenotypic Rescue of Neuronal Structure and Function in a Rett Syndrome Mouse Model
Rett syndrome is a debilitating neurodevelopmental disorder that affects between one in 10,000 to one in 15,000 females. Symptoms that appear in early childhood include severe mental disabilities, impaired speech and movement, and seizures. Individuals with Rett syndrome show abnormalities in the size and structure of certain neurons in the brain. At present, there is very little treatment available for this disease. In most patients, Rett syndrome is caused by mutations in a single gene called MECP2. David Stussâ research is part of a collaborative effort that is investigating methods for introducing a functional form of this gene into the brain at the appropriate developmental stage. This is expected to allow neurons to follow their normal course of growth and maturation. The methods being developed use engineered lentivirus vectors that are capable of delivering genetic material into differentiated, non-dividing cells like neurons. These viral vectors can also introduce genes for fluorescent proteins into targeted cells at the same time, allowing detailed microscopic visualization of the effects of treatment on neuronal structure. If the rescue of neuronal structure and brain development following therapeutic gene transfer can be demonstrated, this research will be an important first step in creating a therapeutic strategy for treating the devastating effects of Rett syndrome in children.
Mechanisms of calcium waves and their contribution to vasomotion in the cerebral circulation
Calcium that is released from one part of a smooth muscle cell can sometimes travel along the length of the same cell in a wave-like manner. This phenomenon is known as a calcium wave. Under certain conditions, a calcium wave can synchronize with other calcium waves from neighbouring cells to cause rhythmic contractions of blood vessels, known as vasomotion. Why vasomotion occurs is not completely understood, but it may be important in controlling blood flow in small diameter blood vessels, such as the cerebral arteries in the brain. Cerebral arteries regulate the flow of blood to working areas of the brain, but this flow is compromised during conditions such as stroke, hypertension or diabetes. There is evidence that the frequency of vasomotion is affected in these conditions. Harley Syyong is studying vasomotion and its underlying mechanisms. Using both molecular and ultrastructural methods, he is exploring the contribution of calcium waves to vasomotion. This research will explore how calcium waves are generated, their role in vasomotion and how the physical structure of the cell supports their propagation. This project is laying the groundwork for future studies to examine how the underlying mechanisms of vasomotion are affected during pathological conditions such as stroke, hypertension and diabetes. Ultimately, this may lead to new drug therapies for treatment of these conditions.
Identification of Mycobacterium tuberculosis virulence factors by pathogen effector protein screening in yeast (PEPSY)
Tuberculosis is a devastating disease that infects one-third of the worldâs population, leading to eight million new cases and three million deaths per year. The prevalence of this disease is largely due to the ability of Mycobacterium tuberculosis (the bacteria that causes tuberculosis) to evade destruction by the immune system. Normally, when bacteria invade the body, the human response system triggers specialized cells called macrophages to engulf and destroy bacteria. In the case of tuberculosis, M. tuberculosis succeeds not only in escaping annihilation, but is able to enter and live inside the very cells that are programmed to destroy it. Using yeast as a model organism, Emily Thi is studying and identifying the components of the arsenal that Mycobacterium tuberculosis uses to successfully infect and survive within human macrophages. Her research on M. tuberculosis proteins that disrupt normal macrophage function may lead to the identification of novel targets for drug and vaccine development, which could result in new strategies to combat this challenging disease.
The Role of CREB in Long-term Memory in Caenorhabditis elegans
Currently 30 million Americans suffer from some form of clinically recognized memory disorder. During the last 25 years, basic neurobiological research has begun to identify the underlying molecular mechanisms for memory formation. One of the key players discovered to be involved in the formation of protein synthesis dependent long-term memory (LTM) is the transcription factor cAMP response element binding protein (CREB). CREB has been shown to be a necessary protein for the formation of LTM in diverse species including sea hares, fruit flies, mice and humans. Tiffany Timbers is exploring whether CREB is also essential for the long-term habituation observed in Caenorhabditis elegans (a tiny nematode), which can become âused toâ repeated stimulation such as tapping on the Petri dish where it lives. Tiffany will determine whether CREB activity (resulting in the transcription of cAMP responsive genes) occurs in the neurons that generate the plasticity responsible for LTM. By investigating the involvement of CREB in the biological pathway underlying the memory of habituation in C. elegans, this research could contribute to the development of new gene targets, drug screens and preclinical data to suggest drug classes capable of helping those affected by memory cognition defects.
The Cell Biology of the NIMA-Related Kinase Defective in Polycystic Kidney Disease
Polycystic kidney disease (PKD) affects one in 800 people worldwide and is the major reason for dialysis treatment and kidney transplantation. One of the most common genetic diseases in the world, PKD has many forms, ranging from aberrant cell proliferation in the kidney to defects in other organ systems, such as the liver and pancreas. This abnormal growth within kidneys and other organs eventually leads to organ failure. The age of onset and disease severity for PKD are highly variable and are affected by additional genetic mutations. Mouse models of the disease have been used to identify many of the genes involved in the polycystic pathology and to determine links between gene and disease. Many of these genes encode proteins that localize to the cilia, a hair-like cell projection that senses the extracellular environment of the cell. The loss of a cilium results in the inability of a cell to response to external cues controlling normal growth. It has been shown that the failure of a kidney cell to build cilia results in PKD. Nek8 is an enzyme which, when mutated, causes PKD in mice. Melissa Trappâs work has shown that Nek8 is also found within the cilia. This research project is focused on the role of Nek8 within cells, particularly how mutated Nek8 can alter the cilium and cause defects in cell growth. By manipulating the protein levels in Nek8 within cultured kidney cells and introducing mutant forms of Nek8, she is examining the effects on ciliary assembly and cell proliferation. This research will contribute to the body of knowledge accumulating about Nek8 and the cause of PKD. It could also contribute to our understanding of other cystic kidney diseases.
Determination of the Effect of Cardiac Ischemia on Ion Channel Kinetics Using Real Time Voltage Fluorimetry
Potassium channels play an essential role in controlling the activation of neurons (nerve cells), myocytes (muscle cells) and the endocrine system. In particular, their proper function and behaviour in the heart is of the utmost importance in maintaining proper cardiac function. Acidosis (a lowering of blood pH) is caused by cardiac ischemia, or an insufficient blood supply. It has been shown that acidic pH levels alter ion channels, possibly through a structural change in the pore region. This condition is linked to cardiac abnormalities such as arrhythmias and cardiac arrest. Moninder Vaid is focusing on acidic alteration of cardiac ion channel function to determine how pH modulates ion channel structure. He using fluorescent techniques to further examine how ion channels work in mammals. Ultimately, this research will provide insight into the effects of cardiac ischemia.
Exploring RNAi technology for the treatment of Huntington's disease
Huntingtonâs disease (HD) is a debilitating genetic disease affecting approximately one in 10,000 individuals. HD is the most common inherited brain disease and is caused by an abnormal protein called mutant huntingtin (muHtt). Symptoms of the disease include cognitive impairment, motor dysfunction and psychiatric disturbances that usually develop around midlife. Many treatments are under investigation in mouse models of HD to potentially cure this debilitating disease. While some pharmacological agents show promise in treating HD, most act on isolated or late-onset symptoms that fail to target the diseaseâs greatest underlying pathological insult, the muHtt protein itself. Laura Wagnerâs research is exploring RNA interference (RNAi), a natural cellular mechanism with intriguing therapeutic potential to block production of the muHtt protein in hopes of slowing or preventing HD symptoms before they start. She is using a transgenic model of HD to test RNAi constructs and their ability to prevent muHtt expression in the brain. The model will be monitored for brain changes as well as behavioural and motor function improvements as indicators of the effectiveness of RNAi treatment. In addition to testing a novel treatment for HD, this research will contribute to continued efforts in advancing medical care from a late-stage symptomatic approach to earlier, preventative therapies such as gene-targeted treatments.
Neurexins and Neuroligins in Synapse Development
Messages are relayed through the nervous system by release of neurotransmitters from an axon of one neuron, which travel across the synaptic cleft and bind to receptors on a dendrite of the next neuron. The axon terminal, synaptic cleft and dendrite are collectively called the synapse. The formation of synapsesâknown as synaptogenesisâis the most central process in the development and maintenance of the nervous system. New synapses are formed during learning and memory and the maintenance of synapses can be altered in disease and drug-induced states. Katherine Walzakâs research is focusing on the process by which synapses form and change with experience. Specifically, she is exploring how neurotransmitter receptors on postsynaptic dendrites are aligned with neurotransmitter release sites on presynaptic axons, and how cell adhesion molecules influence synapse differentiation and localization. By understanding the mechanisms by which synapses forms and are maintained, this research may lead to further insights into disease that may involve the alteration of synaptogenesis, such as Alzheimerâs, schizophrenia and autism spectrum disorders.