About two per cent of men are infertile due to defects in sperm production. In most cases, the underlying cause is unknown. During sperm production, two similar chromosomes – microscopic bodies that carry heredity DNA – pair up and exchange genetic material in a process called meiotic recombination. Recent studies have shown that recombination rates are significantly reduced in infertile men. Infertile men are also more likely to produce sperm with extra or missing chromosomes (called aneuploid sperm). This aneuploid abnormality is the most frequent cause of miscarriage, and among live births, the most common cause of congenital malformations. Kyle Ferguson is using leading edge technology to determine if and how aberrant recombination causes infertility. He is also investigating the recombination patterns that lead to production of aneuploid sperm. This information will help identify genetic mutations that contribute to male infertility, and may lead to new therapies for the condition.
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The relationship between emotion processes and health in children at-risk for the development of anxiety disorders
While feeling shy, uncertain, or apprehensive with strangers or in new situations is common in young children, an excessive display of these behaviours can negatively affect day-to-day functioning. Disruptions in friendships and social activities, decreased school attendance and performance, and increased family conflict are all common consequences of extreme shyness. Research shows that children who consistently respond in these ways are more likely to develop anxiety disorders later in childhood and adolescence. Furthermore, older children and adults who display this pattern of behaviour have more general health complaints and problems. Sherri Frohlick is conducting a study aimed at understanding the development of these general health complaints by examining the ability of preschool-aged shy children to understand and express different emotions, and determining the effect of this on their health status. Just as being able to identify and communicate different emotions is an important part of healthy psychological growth, not having these skills is linked to emotional and behavioral problems such as depression, anxiety, aggression or other serious forms of psychological dysfunction. By examining emotion identification and communication as processes underlying health complaints and problems in young children, Sherri is working to develop prevention and intervention programs that identify their needs more directly and lessen health concerns. A reduction in health complaints would lessen the burden on a health care system faced with the challenge of diagnosing and treating these problems.
The role of dopamine in learning and memory in Caenorhabditis elegans
Dopamine is a chemical (neurotransmitter) that transmits signals between brain cells. Dopamine is involved in motor control, emotion, motivation, cognition, learning and memory. Fluctuations in the level of dopamine in the brain is associated with many conditions that involve deficits in learning and memory, including schizophrenia, Parkinson’s disease, attention deficit-hyperactivity disorder (ADHD) and drug addiction. Andrew Giles is studying how dopamine acts to produce learning and memory in C.elegans, a microscopic worm with a nervous system similar to that of humans. Andrew is examining how changes in the levels of dopamine affect the completion of learning and memory tasks. This information will help explain how dopamine functions in human learning and memory, and its role in normal and abnormal behaviours. The results could support the development of new treatments for disorders involving memory and learning deficits.
Investigating Socio-Cultural and Structural Forces Affecting Sexually Transmitted Infection Testing and Treatment Among Youth in Northeastern BC
Despite public health efforts, sexually transmitted infection (STI) rates among young people are high and rising, with some groups of youth disproportionately affected. In particular, STI’s are a growing concern for youth living in northeastern BC’s oil, gas, and mining communities. These communities are experiencing rapid growth and social change, largely associated with an influx of young people attracted by the current economic ‘boom’ in the oil, gas and mining industries. Shira Goldenberg is investigating young people’s experiences accessing STI testing and treatment services in Fort St. John, British Columbia. She is examining how socio-cultural factors, such as social norms, gender, ethnicity, religion and structural forces, such as geography, economic restructuring, and public health service delivery mechanisms, affect young people’s experiences with STI testing and treatment. Shira will use this information to recommend ways public health planners can tailor STI interventions to improve the sexual health of youth in northeastern BC and other remote, resource-based communities.
Regulation of antibiotic resistance and virulence by two-component response regulators in Pseudomonas aeruginosa
The bacterium Pseudomonas aeruginosa is a major cause of hospital-acquired infections and chronic cystic fibrosis lung infections. This pathogen is difficult to treat because it has the ability to sense and appropriately respond to changing environmental conditions. For example, it can sense and respond to the presence of antibiotics by becoming resistant, making the eradication of established infections extremely difficult. P. aeruginosa infections in cystic fibrosis patients are almost always deadly. An underlying mechanism for antibiotic resistance involves two-component regulatory systems – containing a sensor kinase and a response regulator – that enable bacteria to sense and respond to environmental signals. Two of these regulatory systems within P. aeruginosa have previously been shown to be involved in antibiotic resistance. Jamie Gooderham is determining whether other closely-related P. aeruginosa two-component regulatory systems are also involved in virulence and antibiotic resistance. To do so, he is generating bacteria defective in these systems and studying their virulence, gene expression, and responsiveness to antibiotics. These studies will increase understanding of how this pathogen adapts to environmental signals to develop antibiotic resistance. Ultimately, this will lead to more effective P. aeruginosa therapies, improving treatment outcomes for infected patients.
Respiratory system limitations during exercise in women undergoing healthy aging
There is evidence to suggest that healthy men and women experience respiratory system limitations during exercise, such as respiratory muscle fatigue, a limited ability to exhale, and an abnormal exchange of oxygen and carbon dioxide in the lungs. Young active women may be particularly susceptible to these limitations due to their inherently smaller lungs and airways compared to men of equal stature. Unfortunately, there have been few studies aimed at understanding how the female respiratory system responds during exercise. Since healthy young women are predisposed to these limitations during exercise, then healthy elderly women may be particularly vulnerable due to the decline in lung function that occurs as a result of the normal aging process. This decline occurs because of a reduction in “elastic recoil,” which is the ability of the lungs to stretch and inflate. Jordan Guenette is studying the relationships between the respiratory system, exercise, gender, and healthy aging. His goal is to identify the respiratory limitations women face as they age. This information could be used to design exercise rehabilitation programs tailored to meet the needs of different patient populations.
SHIP Down-Modulation as a Potential Approach to Protect Hematopoietic Cells During Chemotherapy or Radiotherapy
Chemotherapy and radiotherapy are currently used to treat many types of cancer. However, these treatments are not ideal because they target all dividing cells, including both cancerous and healthy cells. Blood cells, for example, have a finite lifespan and new cells are continuously being generated in the bone marrow. Unfortunately, the high doses of chemotherapy or radiation necessary to destroy malignant cells also kill these bone marrow cells. This reduces the body’s ability to replenish healthy blood cells, leading to life-threatening side effects such as anemia, infections, and uncontrolled bleeding. In such cases, the chemotherapy or radiation dose must be reduced, which, in turn, reduces the likelihood that cancerous cells will be eradicated. Melisa Hamilton is studying ways to protect blood cells during cancer treatment, with a particular interest in understanding how the SHIP protein inhibits blood cell survival. Melisa wants to determine whether reducing the level of this protein can increase cell survival during treatment. This would enable patients to withstand higher doses of chemotherapy or radiation with fewer side effects and increase the likelihood of killing the cancer cells.
Cognitive Bias in Subsymptomal Seasonal Affective Disorder
Canadians, like other people living at higher latitudes, often experience seasonal changes in sleeping patterns, appetite, mood, and energy levels between the winter and summer seasons, but there has been little research to explain why. Fern Jaspers-Fayer is studying the impact of season on thoughts, moods and behaviour. These changes occur along a continuum from normal to abnormal, with severe winter depression, or Seasonal Affective Disorder (SAD), at one extreme. Fern is identifying the changes in electrical brain activity associated with SAD, and will determine whether these changes disappear in the summer. The results should help explain the brain mechanisms involved in SAD, leading to better therapies for the condition and better ways for everyone to chase away the winter blues.
Somatic and gametic loss of imprinting (LOI) in mammalian development: studies using a novel imprinted transgene on the mouse distal choromosome 7 (MMU7) imprinted region
Genetic inheritance in an offspring primarily results from the interplay of dominant and recessive genes between two parents. With certain genes, however, gene expression is parent-of-origin-specific: these genes will always be expressed from either the maternal or paternal chromosome. This process is known as genomic imprinting, which creates a mark, or “imprint”, on the chromosome. Loss of imprinting (LOI) is often studied in the context of disease, especially in cancers, but it is also a normal part of development. For example, in germ cells, imprints are erased and re-set early in development every generation, resulting in a normal period of LOI. Meaghan Jones is investigating a hypothesis that non-germ cells may also experience some normal LOI during development. She will examine the timing, stimulus and duration of LOI in germ cells and somatic cells during development. By determining the various causes of LOI in both types of tissues, she hopes to uncover factors regulating normal LOI and help alleviate the risk of imprinting defects.
Notch signalling in mammary tumorigenesis
Breast cancer is the most common cancer among Canadian women. One in nine women is expected to develop breast cancer in her lifetime, and one in 27 will die of the disease. Metastasis, or the spread of the tumour to another site, is the major cause of death. Notch receptors are cellular proteins required for normal growth and development. However an overproduction of an active component of Notch can cause abnormal cell growth, leading to tumour formation and the spread of cancer to distant sites. Iva Kulic is examining how another protein, called Slug, functions with Notch to promote breast cancer. Both Notch and Slug are found at high levels in some human breast cancers and are a sign of poor outcome. Slug prevents tumour cells from dying and allows them to detach from neighbouring cells and travel to other sites within the body – two key features in tumour development and metastasis. This research will explore whether reducing or eliminating the Slug protein will inhibit breast tumour growth and block the spread of cancer cells. Resolving whether Slug is essential in Notch-induced breast cancer could lead to new ways of preventing and treating the disease.