Biochemical and structural characterization of bacterial type III secretion system components

Harmful bacteria are becoming much more resistant to the currently available antibiotics, a situation that poses a serious threat to public health. The development of new and more effective ways of protecting against these increasingly dangerous (and antibiotic resistant) microbes requires a thorough understanding of the molecular mechanisms through which they cause disease. The bacterial type III secretion system (TTSS) is a complex mechanism that controls how bacterial proteins are transfered into human cells, a process that is essential to the disease-causing capabilities of a large number of pathogens, including Salmonella and pathogenic E.coli. Although many components of the TTSS have been identified, exactly how this secretion system is assembled and how virulence proteins (toxins) are delivered into target cells remains poorly understood. With support from a 2002 MSFHR Trainee Award, Calvin Yip successfully described the first high resolution structure of an extracellular component of the TTSS. Now funded for a second time, he is working to further characterize its structure and function. This work will help answer fundamental questions about the biochemical and structural characterization of TTSS, and may facilitate the design of new classes of drugs to combat a broad range of infectious agents.

Social effects on a linguistic mechanism in Autism Spectrum Disorders

Children and adults with one of the group of pervasive developmental disorders known as Autism Spectrum Disorders (ASD) have difficulties with language and social interaction. Language problems are especially disabling, as most activities rely on language. Katherine Yoshida is researching whether the ability to learn language is impaired in people with ASD because it is generally learned through social cues and interaction. Children, for example, may follow a parent’s eye movement to associate a word with an object. But children with ASD often do not make eye contact. Katherine is investigating whether reliance on social interaction to develop language impedes learning in people with ASD. The research could confirm that people with ASD learn language more effectively in non-social settings, and the results could be used to develop alternative learning strategies that improve communication abilities in people with ASD.

The effects of proportional assist ventilation on ventricular interaction in patients with heart failure, endurance athletes, and healthy individuals during exercise

About 350,000 Canadians suffer from chronic heart failure (CHF), which can cause premature death. The condition usually progresses slowly as the heart gradually weakens and loses its ability to efficiently pump blood through the body. Patients with CHF develop an enlarged heart and experience “pericardial constraint”: inadequate performance in the ventricles, the heart’s two pumping chambers. The pericardium is a tough, fibrous sac surrounding the heart. Endurance athletes may have an enlarged, more compliant pericardium that allows them to achieve superior levels of cardiac performance during exercise. But with chronic heart failure, the pericardium becomes taut and restricts the heart from fully filling with blood and delivering oxygen to the body. Ben Esch is investigating whether providing oxygen through a mechanical respirator to increase pressure in the chest will decrease pericardial constraint and improve cardiac function in people with CHF. The results could lead to new rehabilitation techniques for patients with chronic heart failure.

Facial processing within the temporal lobes following cerebrovascular infarct: a neuropsychological, anatomical, and functional study

Vision encompasses a very complex sensory system which requires the involvement of multiple brain areas to function properly. Damage to any one of these areas can affect vision in very specific ways. For example damage to a very small and precise region in the brain, found within the posterior temporal lobe, results in a specific perceptual deficit, manifest by an inability to recognize faces. It is common for patients who have suffered from a stroke to experience this or other visuo-perceptual impairments. Based at UBC’s Eye Care Centre, Christopher Fox is examining stroke patients who have temporal lobe damage. Using a variety of tests he is determining visual processing deficits in these patients, then using MRI (Magnetic Resonance Imaging) to examine their brains to see which regions are responsible for these deficits. Christopher’s research will contribute to a greater understanding of the role of the temporal lobes in vision, and of the complex process of visual perception.

Bringing risk prevention models into the bedroom: Sex appraisals, coping and their roles in condom use consistency

HIV transmission remains a threat in Canada and around the world. Men who have sex with men account for 41 percent of all new cases of HIV in Canada, and continue to be the largest proportion of new cases. However, recent trends suggest nearly 30 percent of new HIV cases occur among heterosexuals following sexual contact. Although new HIV drugs have brought hope to patients, they have also lessened the perception of HIV risk. In fact, new cases of HIV infection increased 17 percent in 2002, compared to 2000. Eli Puterman is developing a new model to predict and understand safe sex practices in two at-risk groups: heterosexuals with multiple partners, and men who have sex with men. While present HIV prevention models can predict the intention to use condoms, they are less successful at predicting whether condom use will actually occur, because they do not consider the uniqueness of each sexual encounter. Instead, Eli is investigating how individuals appraise and respond to HIV risk in different sexual situations over time. This research could provide a new model for HIV prevention strategies both within Canada and other developed countries.

The effects of individual, educational, and organizational factors on the job satisfaction, social adjustment, and career turnover of newly graduated registered nurses

Registered nurses (RNs) account for 75 percent of health care professionals. Statistics Canada predicts that demand for nursing services is expected to rise as much as 46 percent by 2011. But new nurses are leaving at an alarming rate: 15 to 21 percent of newly qualified RNs are lost to other careers or immigration. Action is needed to meet projected needs for nursing services, but little is known about the factors that affect nurses’ career decisions. Angela Wolff is surveying student nurses about the individual, educational and organizational factors that influence job satisfaction, social adjustment to the workplace, and career choices. Angela is evaluating whether professional autonomy, nursing control over the practice environment, and open, effective channels of communication are directly related to job satisfaction and commitment. This research will identify barriers to integrating new RNs into the workforce, and ways to develop a supportive work environment for beginning practitioners. Ultimately, these strategies could enhance recruitment and retention of new nurses to help address an impending shortage of nursing staff in Canada.

Mechanisms of attention: implications for brain and behavior

Our attention can be shifted automatically in response to sudden events, such as a hand being raised in a classroom, or can be allocated voluntarily in response to our internal goals and expectations, such as looking left or right before crossing a street. Dysfunction of either type of attentional process may be expressed in a variety of disorders, such as schizophrenia, Parkinson’s disease, autism, and attention deficit disorder. Currently, diagnosis and rehabilitation of attention in patients relies on behavioral procedures that were established more than 20 years ago. Jelena Ristic’s recent research, conducted with both children and adults, suggests that these traditional procedures are based on flawed theoretical assumptions and as such, they do not reflect the main properties of human attention. She is currently working towards developing novel behavioral, as well as imaging, methodologies that will capture accurately the key properties of human attention. Results from her basic research will be used to develop more effective diagnostic techniques and rehabilitation programs for patients with attention dysfunctions.

Caenorhabditis elegans dog-1 gene mechanism in genome stability

Genes that contribute to normal cell reproduction, growth and DNA repair are essential for healthy cell function in all organisms. The dog-1 gene plays a role in maintaining the stability of the genome of Caenorhabditis elegans, a tiny worm frequently studied by researchers because it has many molecular characteristics that are central to human biology. However, little is known about how the dog-1 gene functions to maintain genome stability. Jillian Youds is studying how this gene functions in the cell to gain a better understanding of how it contributes to DNA sequence stability. Given that mutations in the genes required for stability are often underlying causes of disease, this research could provide further understanding of the development of cancer.

Competition for control of behavior

Behavioural responses are influenced by information from a person’s immediate environment and an individual’s goals and intentions. Conflict between these sources occurs regularly, and is particularly evident in eye movements, in which split-second decisions about where to look next are made more than 100 times a minute. Many neurological and psychiatric disorders such as schizophrenia, Parkinson’s disease, Alzheimer’s, depression and anxiety are characterized by inefficient or inappropriate eye movements and other behaviours. Amelia Hunt is studying the physiology of eye movements to assess how conflicts between intentions and sensory responses are resolved. She is also investigating whether models of eye movement control can apply to other complex behaviours and disorders. The research could inform and guide intervention strategies to be used when behavioural controls begin to break down from illness or trauma.

Acid extrusion from rat hippocampal neurons; the potential role of a voltage-gated proton conductance

Intracellular pH, the amount of acid inside neurons (brain cells) changes during normal cellular activity and with conditions such as stroke. Left unregulated, these changes can alter brain cell function and contribute to their death following a stroke. Consequently, cells have developed mechanisms to maintain their intracellular pH within normal limits. The hippocampus, a part of the brain associated with learning and memory, contains some cells that are very susceptible and some that are very resistant to stroke-related cell death. Research has identified three mechanisms that regulate pH in hippocampal brain cells, but recent evidence suggests that these mechanisms are inhibited during a stroke. May Cheng is investigating whether there is a fourth mechanism, a voltage-gated proton conductance, that regulates pH by discharging detrimental acid from these cells. Identifying this additional mechanism could lead to new strategies to prevent or limit brain cell death following a stroke.