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.

Probing the preparation and preprogramming of voluntary movements using startle in healthy humans and clinical populations

Every day people are required to make quick, voluntary responses to environmental signals, such as sound. The higher brain (cerebral cortex) has long been thought to control these movements by receiving and analyzing sensory information and coordinating responses. But Anthony Carlsen’s research has shown reactive movements can be stimulated more quickly with a loud, startling sound at 124 decibels. The research suggests it may be possible to pre-program these quicker responses and store them in the midbrain, the area that controls auditory and visual reflexes. Anthony is using Functional Magnetic Resonance Imaging (fMRI) to determine if there is brain activity with pre-programmed responses in the midbrain. He is also testing whether the startling sound triggers a midbrain response in people with Parkinson’s disease and those who become deaf following a stroke. Results from the study could provide insights about human motor control, the source of movement deficiencies caused by Parkinson’s, and potential treatments for people with Parkinson’s and cerebral deafness.

The link between cardiovascular and bone health: a randomized controlled trial of statins and exercise rehabilitation in post-menopausal women

Cardiovascular disease (CVD) and osteoporosis are major health problems in North America. CVD is the leading cause of death of North American women, and one in four Canadian women over the age of 50 has osteoporosis. Once a woman reaches menopause, the risk for both osteoporosis and CVD increases substantially. Both diseases were thought to be independent consequences of aging. However, mounting evidence shows links between these diseases. For example, a widely used class of cholesterol lowering drugs, known as statins, reduces atherosclerosis (hardening of the arteries) and also increases bone health. Exercise may also provide the same health benefits, but more than 60 percent of Canadian women between 50 and 70 are not active enough to reduce their risk of heart disease or osteoporosis. Dr. Darren Warburton is studying the combined effect of statins and exercise on cardiovascular and bone health, physical fitness and quality of life. The research could provide important new information to help develop prevention and treatment programs for these diseases in post-menopausal women.

Child and Youth Developmental Trajectories Research Unit

Economic circumstances, family environment, neighbourhood conditions, cultural influences and biology all play a part in child and youth development. Because health, education, community and socioeconomic data have traditionally been tracked separately, researchers have not had the capacity to fully investigate the complex factors that affect the development of children and youth in BC. The new data system developed by the unit will change that, giving BC greater capacity than any other jurisdiction in the world to track the factors that support or undermine children’s cognitive, social, emotional and physical development, from the prenatal period through to early adulthood. This dedicated research team will expand the work of the Human Early Learning Partnership (HELP) based at UBC, which is an interdisciplinary network of more than 150 faculty, researchers and students from universities across BC that examines development across the lifespan.

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Mechanism of myocardial dysfunction in sepsis

More people die each year from sepsis, a severe, overwhelming infection and inflammation, than from breast or colon cancer. The infection is also 20 times more deadly than a heart attack. Septic shock (severe sepsis) causes multiple organ failure and is the leading cause of death in North American intensive care units. Sepsis impairs the heart’s ability to use oxygen, which is necessary for the heart to pump normally. Dr. Ryon Bateman is investigating whether damage to capillaries (the smallest blood vessels) prevents oxygen from being delivered within the heart or whether dysfunction of the mitochondria (the parts of the cell that consume oxygen) prevents oxygen from being used by the heart. Dr. Bateman is using advanced microscopic imaging techniques to generate three-dimensional images of heart capillaries to look for changes in their number and spacing. He is also assessing whether regions of the heart with low oxygen have tissue damage, and if mitochondria are damaged in these regions. The research could explain why the heart is damaged during sepsis, leading to new treatments for critically ill septic patients.

The role of antigen presenting cells in viral induced autoimmune diabetes

An autoimmune response occurs when the body’s immune system mounts an attack on its own organs or tissues. Type 1 diabetes, for example, results when immune cells destroy insulin-producing cells in the pancreas. Although genetic predisposition is a major factor, seemingly benign viral infections also may play a role in this disease. However, the mechanisms by which viral infections cause autoimmune disease remain unclear. Martin Richer is researching how viruses cause autoimmune type 1 diabetes. He is investigating the mechanisms by which the immune system is sensitized by exposure to a virus and mounts an attack on normal cells. Martin is also studying how this activity influences the development and progression of disease, and how the process can be regulated. The findings could improve understanding of how viral infections lead to autoimmune responses and diseases such as type 1 diabetes.

Shaping the outcome of viral-mediated autoimmune myocarditis

Coxsackievirus infections can cause a variety of illnesses, including heart disease. In North America, the coxsackievirus is estimated to cause up to 30 percent of new cases of dilated cardiomyopathy, a condition in which the heart becomes enlarged and pumps less strongly. Dr. Marc Horwitz is studying how viruses such as coxsackievirus can induce autoimmune diseases such as chronic heart disease, and how immune system components shape and control development of the disease. Studies have shown that the body’s immune response has a profound effect on the development of chronic heart disease after infection with the virus, revealing that immune cells and antibodies that attack infection also damage heart tissues. Dr. Horwitz is examining how innate and adaptive immune responses following viral infection contribute to development of chronic heart disease. He will use findings from the study to design and test new methods to prevent heart disease, which could also lead to new treatments.

The public health impact of obstructive sleep apnea hypopnea – a focus on work productivity, occupational injuries and motor vehicle crashes

Sleep is an integral part of our lives. Inadequate or poor quality nightly sleep has many adverse health and safety consequences. The most important medical disorder that disrupts sleep is obstructive sleep apnea hypopnea (OSAH), a common, under-diagnosed condition characterized by recurrent collapse of the upper airway during sleep (up to 100 times per hour). Symptoms of the disease include loud snoring, nocturnal choking, poor quality sleep, recurrent awakenings, daytime sleepiness, impaired alertness, reduced quality of life, hypertension and strokes. Therapy to prevent the upper airway from collapsing can reverse many of these symptoms. Dr. Najib Ayas’s work is focused on investigating the pathogenesis, diagnosis, therapy, economic impact, occupational impact, public health, and safety consequences of sleep disorders, with a particular focus on OSAH. For instance, by developing a comprehensive registry of patients with OSAH, he hopes to determine whether patients with OSAH suffer from reduced work productivity and higher rates of occupational injuries and motor vehicle crashes; and whether therapy reduces these risks. Findings could then be used to develop screening and treatment guidelines for OSAH, and occupational and transportation policy recommendations. In the future, this unique registry will help identify biochemical cardiovascular risk, genetic and biochemical factors associated with OSAH.

Identification of potential molecular markers and therapeutic targets involved in the progression of mantle cell lymphoma

Mantle cell lymphoma (MCL) is an aggressive cancer of the lymphatic system that is incurable with chemotherapy or radiation. MCL has a survival rate of approximately three years, with no long-term survivors. Ronald deLeeuw is studying the biology of this disease to learn more about how it progresses. He is focusing on secondary genetic alterations concurrent to a characteristic feature of MCL: the switching of a genetic segment from one chromosome to another (translocation), which results in uncontrolled growth of lymphatic cells and an unregulated growth signal. Using new technology that reveals previously undetectable genetic changes, Ronald is compiling a comprehensive list of secondary genetic alterations that could contribute to progression of MCL. The research could provide insights about potential targets in treatment of MCL.

Identification and functional characterization of actin-related proteins associated with Salmonella containing vacuoles

Salmonella bacteria cause a number of serious illnesses, including typhoid fever, which kills over 600,000 people worldwide every year, and gastroenteritis. When Salmonella bacteria infect human cells, they use the cell’s proteins for their own survival. To accomplish this, the bacteria form a protected area within the host cell that allows them to survive and multiply. A major protein surrounding that protected area is called actin. Dr. Julian Guttman is investigating what other proteins interact with actin and how they affect Salmonella bacteria’s ability to cause disease. The research could provide the foundation for creating Salmonella vaccines or other drugs to eliminate Salmonella-based illnesses.