Salmonella species cause a variety of diseases, including diarrheal and systemic illness, signicificant causes of morbidity and mortality in the developing and developed world. To cause disease in healthy people, bacteria such as Salmonella typhimurium must first breach physical barriers, such as the mucous membrane lining internal organs, and then successfully avoid detection and destruction by the immune system. Gastroenteritis (inflammation of the stomach and intestine) in healthy humans and systemic illness in people with compromised immune systems result from the successful evasion of Salmonella typhimurium. Resistance to infection depends on a wide array of immune factors. Bryan Coburn is researching the role of host resistance factors and also the response of bacteria to these defenses in Salmonella-induced gastroenteritis. The research will potentially provide important insights about the mechanisms that influence susceptibility or resistance to Salmonella-induced gastroenteritis.
Research Location: University of British Columbia - Point Grey
Prospective memory in obsessive compulsive disorder
People with obsessive compulsive disorder (OCD) experience persistent and distressing thoughts. In most cases, anxiety is relieved by performing repetitive acts, such as washing, checking or counting. Obsessive thoughts and compulsive behaviours can occupy so much time that people with OCD have difficulty functioning at work, taking care of themselves and relating to others. At its most extreme, OCD requires hospitalization. Carrie Cuttler is investigating whether impaired prospective memory — the type of memory required to remember an intention such as turning off the stove or taking medications — is linked to compulsive checking. Studies have shown prospective memory is impaired in patients with schizophrenia and depression, but little is known about the influence of anxiety on this type of memory. Carrie’s research could lead to more effective behavioural interventions that reduce the frequency of compulsive checking and improve quality of life for OCD patients.
Assembly of Postsynaptic Protein Complexes in Hippocampal Neurons
Synapses, the connections that enable brain cells to communicate with each other, are fundamental to normal brain function. Studies suggest synapses form and mature quickly—in a few hours—but the molecular interactions that trigger this process in the central nervous system are unclear. Kimberly Gerrow is researching the molecular stages of synapse development in the hippocampus, a part of the brain involved in cognitive functions such as learning and memory. She is investigating the role of PSD-95 protein (postsynaptic density protein), in assembling molecules crucial for creating synapses. This could lead to improved understanding and treatment of neurological disorders that result from interruptions or abnormalities in synaptic development. The findings could also offer insights into ways of re-establishing functional brain connections that have been damaged by conditions such as stroke, Parkinson’s and Alzheimer’s disease.
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.
Mechanistic investigations of Family 4 Glycosidases
Carbohydrates traditionally were thought to serve one role: reservoirs of energy for maintaining metabolism. In fact, they serve much more diverse and vital roles, including regulation of cellular activity. Vivian Yip is studying Family 4 glycoside hydrolases, a family of enzymes that break down carbohydrates in bacterial cells. These enzymes are part of a system that transports sugar molecules across the cell membrane and into the cell. Inside the cell, the enzymes cut the sugar into smaller pieces to provide food for the bacteria. Vivian is investigating the chemical mechanism of these enzymes, which will provide important clues to inhibiting the enzymes’ activity. Inhibition of these enzymes could restrict the food supply, which would cause bacterial cells to die. Findings from the research could be used to develop antibiotics to reduce bacterial infections with potentially few side effects since currently these enzymes are found only from bacterial sources, but not mammalian.
Regulating antibiotic resistance in Staphylococcus aureus: elucidation of the mechanism of BlaR1 through X-ray crystallography
The discovery of penicillin in the early 1900s offered the possibility of a “magic bullet” for the treatment of bacterial infection. Bacteria have proven incredibly versatile, however, as new strains have evolved that can overcome the newest and most sophisticated antibiotics. Superbugs are strains of bacteria that are resistant to all available antibiotics. Staphylococcus aureus, also known as Staph, is a normally harmless skin-borne bacterium that can be lethal in patients with weakened immune systems. Strains of Staph function as superbugs that can tolerate all but the newest experimental drugs. As fast as new antibiotics are developed, Staph appears able to evolve resistance to them. Mark Wilke is researching the molecular mechanisms that regulate resistance to a class of antibiotics called beta-lactams. The findings could help explain how Staph bacteria switch their antibiotic resistance on and off, as well as lead to new strategies for combating Staph infections.
Effects of changes in joint alignment and loading on cartilage in humans
One in ten Canadians suffers from osteoarthritis, a debilitating and painful disease caused by cartilage degeneration in joints. Abnormal load on the cartilage or some part of it caused by poor joint alignment or obesity can lead to loss of cartilage, which does not usually regenerate on its own. However, it has been shown that cartilage can repair itself following surgery, although the conditions to ensure re-growth are unknown and the reasons for success or failure over the long-term are poorly understood. Using non-invasive magnetic resonance imaging (MRI) scans, Agnes d’Entremont is assessing cartilage health and knee movement in bow-legged patients before and after they have high tibial osteotomy, a surgery to correct their joint misalignment. Agnes aims to define the best conditions for protecting cartilage and promoting repair. The research could increase understanding of osteoarthritis, improve surgical outcomes, and lead to better treatments.
Assessing sensitivity to unobserved confounders in observational studies: a Bayesian approach
Hospitals and other health care organizations collect data in areas including admissions, diagnostic tests, and hospital discharges. Health services researchers use this information because it is abundant, readily available and inexpensive to access. However, this type of data differs from experimental data, which is collected for the purpose of research. With experimental data, half of participants receive a treatment and the other half receives a placebo based on random allocation, which allows researchers to measure the impact of the treatment in a manner which is unbiased. Results may be less reliable for non-experimental data when comparing groups of patients because uncontrolled circumstances can influence the outcomes in a process known as confounding. Lawrence McCandless is examining whether a new approach to using health care databases, Bayesian sensitivity analysis, can improve the accuracy and reliability of statistical studies. Lawrence is investigating the effectiveness of the approach in studying waitlists for coronary artery bypass surgery in BC. The research could suggest ways to more broadly use health care databases to study and improve the health system.
Alternative methods for assessing exposure to occupational risk factors for back injury
Back strain is the leading cause of injury among Canadian workers. From 1997 to 2001, the Workers’ Compensation Board of BC received more than 90,000 back strain claims and paid out more than $661 million in compensation. Major occupational risks for back injury include heavy lifting and awkward postures. Rahul Chhokar is comparing different methods for assessing exposure to these risks in five BC industries that account for more than 25 per cent of back claims: forestry, wood and paper products, construction, transportation and warehousing. Direct measurement systems are costly and not always practical to use, but are generally considered the most precise. Rahul is studying whether other, less expensive approaches also provide reliable data on exposure to occupational risks. These include interviewing workers, asking them to fill out questionnaires, and observing workers at job sites. If accurate, these methods could provide a more cost-effective way of identifying potentially harmful work environments and reducing the risk of injury.
Does a counselor's occupational stress impact client outcome in addiction treatment?
Continuous demand for addiction services, ongoing reorganization, staff shortages and gaps in service have created a stressful work environment for B.C.’s addiction service providers over many years. Little research has been conducted on the work environment of addiction counsellors and on the impact that environment has on client outcomes. Annemarie Gockel is studying the level and impact of the occupational stress experienced by addiction counselors in BC. She is investigating whether stress affects counselors’ ability to form effective working relationships with clients, and whether service provider stress affects client outcomes. Results from the research could be used to enhance the effectiveness of addiction treatment and improve workplace quality for addiction service providers.