Year: 2004

The role of insect immune peptides in limiting disease transmission by vectors

Vector-borne diseases – diseases spread to humans by insect vectors – pose serious health problems worldwide. Malaria, transmitted by mosquitoes, kills 2-3 million people a year; Lymphatiic filariasis, transmitted by mosquitoes, afflicts more than 100 million people; African sleeping sickness, spread by tsetse flies, affects up to 500,000 people each year, most of whom die within two years of infection; Chagas Disease, transmitted by kissing bugs, is found only in the Americas and affects 30 million people and results in premature heart attacks. In North America, West Nile virus, spread by mosquitoes, has expanded to most regions. Insects have a potent immune system that kills most pathogens (disease-causing organisms). A major component of their immune response is the production of small proteins that kill many bacteria, viruses and parasites. Dr. Carl Lowenberger is studying these immune peptides to identify ways to reduce disease transmission to humans, and to determine if these antimicrobial peptides could be used to treat human infections. Many pathogens have developed resistance to antibiotics. Immune peptides isolated from insects in this research could provide a new source of antibiotics to overcome drug resistance.

Contribution of the ubiquitin/proteasome pathway to coxsackievirus-mediated myocarditis

Myocarditis, an inflammatory heart disease caused by the coxsackievirus, can lead to a dilated (enlarged) heart, which can result in sudden heart failure. A heart transplant is the only treatment for this condition. The proteasome is a cellular garbage collector that accumulates and destroys unwanted or damaged proteins. Ubiquitin is a molecule that latches onto damaged or mutated proteins and flags them for destruction by proteasomes. In earlier research, Dr. Honglin Luo showed that blocking the ubiquitin/proteasome pathway prevents the coxsackievirus from producing proteins, which may affect the ability of the virus to replicate. Now Dr. Luo is further investigating the effect of the ubiquitin-proteasome pathway on replication of the coxsackievirus and development of myocarditis. The research could confirm that inhibiting the pathway limits virus replication and prevents abnormal protein degradation, which could lead to new treatments for myocarditis that reduce progression of the disease to heart failure.

Role of the budding yeast kinetochore in chromosome segregation and checkpoint response

Cells must accurately duplicate their chromosomes (genes in the cell’s nucleus) and segregate them equally to daughter cells for proper cell growth and division. Errors in segregation results in cells with abnormal numbers of chromosomes (aneuploidy), which can lead to birth defects, Down’s syndrome and cancer. Cells have developed safeguards to ensure chromosomes are accurately segregated. A region of each chromosome called the centromere is bound by kinetochore proteins which attach to spindle microtubules, tiny fibres that pull newly separated chromosomes to each side of a dividing cell. If any mistakes occur in spindle attachment, kinetochore proteins signal the spindle checkpoint machinery, which delays segregation until the defects are corrected. Using yeast as a model, Dr. Vivien Measday is studying how kinetochore proteins attach to spindle microtubles and communicate with the checkpoint machinery. The research will improve understanding of chromosome segregation and could lead to treatments for diseases caused by abnormal numbers of chromosomes.

Psychoeducation in bipolar disorder: determining the effects of psychoeducation upon recurrence and quality of life in first episode mania patients

More than half a million Canadians suffer from bipolar disorder, a chronic psychiatric condition that causes repeated episodes of depression and/or elation. The condition significantly disrupts social and work lives, with high costs to the health care system. Although medical management of bipolar disorder has improved, many people have repeat episodes requiring frequent hospitalizations, and 15 percent of patients commit suicide. Research on the disorder is beginning to focus on treatments involving psychoeducation as well medication. This approach is designed to provide education about bipolar disorder and its treatment, promote early detection of symptoms, encourage regular sleep-wake cycles and social routines, enhance self-monitoring, and improve stress management skills. Dr. Erin Michalak is studying whether psychoeducation can improve quality of life for patients who have experienced their first episode of elated mood (mania). The research could determine whether psychoeducation helps to prevent relapse, reduce symptoms, improve adherence to medication, and improve ability to function socially and at work. The findings could be used to develop early intervention programs for people newly diagnosed with bipolar disorder.

Health Research of Vulnerable Urban Populations

Up to half of all Canadians with HIV also have hepatitis C, with co-infection highest among injection drug users. Dr. Anita Palepu is researching the impact of drug and alcohol use among people co-infected with HIV and hepatitis C on their adherence to HIV treatment and on treatment outcomes. Dr. Palepu, who focuses on health and social problems faced by vulnerable urban populations such as drug users and homeless people, is also examining the role of addiction treatment in clinical outcomes. In a related project, she is conducting a quality of life study with vulnerable populations such as injection drug users, homeless people and street youth to assess the effectiveness of interventions intended to improve their lives. Dr. Palepu is also part of a national network of researchers evaluating the effects of programs designed to prevent homelessness, or help people exit homelessness, on the health of those considered “hard to house.” The research could inform health and social policies and ultimately help improve the health of vulnerable urban populations.

Identification of circulating cells with a myogenic potential

Degenerative diseases have an enormous economic and social impact on BC’s aging population. In the long term, identifying cells that could regenerate organs damaged by degenerative diseases could revolutionize how these conditions are managed. Care could shift from expensive, lifelong drug treatments to therapies that permanently restore organ function. Research suggests that bone marrow contains stem cells (precursor cells that have the ability to develop into cells specific to types of tissues) capable of repairing damaged tissues in adults. To efficiently use stem cells, however, the cells responsible for tissue repair must be identified from among the many cell types present in bone marrow. Dr. Fabio Rossi is identifying bone marrow cells that repair damaged muscle, exploring their characteristics and investigating how they repair damaged tissue. Findings could lead to therapies that efficiently restore organ function.

Intestinal innate immunity: recognition and response to enteric bacterial pathogens

Bacterial infections of the gastrointestinal tract are very common, particularly among children. These infections cause diarrheal outbreaks and millions of deaths worldwide. Bacteria are also a major problem in Canada, with BC having one of the highest rates of intestinal bacterial infection in the country. Bacteria are believed to trigger a variety of gastrointestinal diseases, including inflammatory bowel disease, a debilitating and chronic condition that affects one in every 1,000 Canadians. Despite the prevalence of bacterial pathogens (disease-causing organisms), little is known about how the immune system recognizes and combats intestinal bacterial infections. This information is important because the immune response to these bacteria determines who is susceptible to infection, as well as the severity of the resulting disease. Dr. Bruce Vallance is researching how bacteria cause intestinal disease and how the immune system identifies and fights these infections. Dr. Vallance is investigating whether genetic differences in hosts influence susceptibility to food and water-borne bacteria. He aims to identify immune responses and genetic factors that either protects against intestinal bacteria or causes susceptibility to infection. This research could help explain how bacteria cause intestinal disease and ultimately lead to new treatments to prevent both bacterial infections and bacterial-induced gastrointestinal diseases.

Bioinformatics for the study of gene regulation

Genetic diseases can result from subtle variations in the DNA sequences of genes. Approximately three million differences exist between the DNA of any two individuals. While most of these differences have no functional impact, researchers have linked numerous variations to diseases. These linkages have provided insight into disease development, enabled the creation of diagnostic tests and accelerated the creation of therapeutics. Most of the known functional DNA variations result in decreased activity of proteins produced by a gene. But Dr. Wyeth Wasserman suspects many functional variations actually alter gene activity, rather than the sequence of proteins encoded by genes. This is because information flows from genes through an intermediate RNA molecule, and is translated to construct proteins. Variations that disrupt this flow could have dramatic consequences. Using bioinformatics (analysis of genetic data using advanced computing algorithms), Dr. Wasserman aims to identify regulatory variations that likely impact gene function and contribute to genetic diseases.

Pharmaceutical Outcomes and Policy Innovation

Canada is facing one of the highest growth rates for drug costs among developed nations. As a result, cost is the primary factor leading public policy decisions for drug insurance programs. Researchers in this unit will conduct studies to systematically assess the effectiveness and safety of prescription drugs in tandem with cost-effectiveness. Their studies will help provide an evidence-based platform upon which policy-makers can make rational decisions about drug plan coverage.

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