Identification of the roles played by NIMA-related kinases in flagellar, microtubule, and cell cycle regulation and signalling in Chlamydomonas

NIMA-related kinases are a diverse family of proteins found in virtually all eukaryotic cells. Single-celled eukaryotes, such as yeast, have a single NIMA family member that helps regulate cell division. A recent discovery that Chlamydomonas, a single-celled green algae, has at least seven family members strikingly contrasts with other unicellular organisms. What sets Chlamydomonas apart from the other unicellular eukaryotes studied to date is the presence of cilia. Mutations in some NIMA kinsases can produce kidney cysts, as do mutations in the proteins essential for assembling cilia, short, hair-like structures that protrude from cell walls and sweep mucus up and out of lungs. In earlier research, Brian Bradley helped identify six new genes in Chlamydomonas. These algae are found all over the world, and are often used for research in cell and molecular biology. Now Brian is using the algae to study the assembly and function of cilia. Brian’s research could help explain the role of NIMA-related kinases in development of kidney disease.

Community, culture and health

Dr. Cindy Patton has conducted a series of studies on knowledge transfer from medical experts to clinicians, media, policymakers and the public. In dramatic and exceptional cases, this exchange happens almost directly. The media’s extensive reporting on health emergencies involving SARS (Severe Acute Respiratory Syndrome) and BSE (Bovine Spongiform Encephalopathy or Mad Cow Disease) created demand from health consumers for more medical research, changes in public health policy, and reassurance about their risk for these conditions. But more often medical research filters down through clinicians and advocacy groups, who translate complex information for consumers and advocate for their medical needs. In addition, government policy makers must sort through information from researchers and citizens to adapt health policies and resources to changing medical needs. Dr. Patton is examining existing methods and systems for exchanging information in various settings—clinics, research centres and global information networks. The research could be used to create better channels for transferring specialized medical information. Dr. Patton is also developing training programs for researchers and the public to help improve their understanding of how to efficiently transfer knowledge from medical experts to people affected by health issues.

Computational and laboratory characterization of genomic islands of potential relevance to bacterial pathogenicity

Infectious diseases cause one-third of all human deaths worldwide. Microbiologists are beginning to get a clearer picture of some of the bacteria that cause disease, using the increasing number of genome (gene) sequences available for these microbes. In fact, a back log of genetic data is waiting to be prioritized and analyzed. The data shows transfer of genetic material between bacteria seems to be much more common than previously believed. Essentially, bacteria can exchange genes that cause disease. In addition, a significant portion of the genes associated with disease are found in clusters called “pathogenicity islands.” William Hsiao believes that focusing on these genomic islands will narrow the search for disease-causing genes in bacteria. He hopes the information will explain how some bacteria cause disease and how they differ from bacteria that do not.

The role of Fa2p in regulating microtubule severing

As an undergraduate student, Moe Mahjoub’s research findings on a gene involved in microtubule severing were published in the Journal of Cell Science, listing him as first author. Microtubules are thin tubes of protein and an essential element of the cell skeleton required for cell division and movement. Moe’s current research is directed at understanding how microtubule severing is regulated, using unicellular algae called Chlamydomonas. Microtubule severing is key to the algae’s shedding of flagella, or whip-like appendages, in response to a wide array of stimuli. This process has important implications for human health. For example, sterility can result when sperm shed flagella in response to ingested toxins. This research could help explain a range of diseases, including retinal degeneration, kidney disease and cancer.

Tracking the B-cell repertoire associated with the broadly-neutralizing antibody response in HIV-1 infection

The progression from HIV infection to AIDS occurs because the body’s immune system fails to control replication of the virus. While broadly neutralizing antibodies (bNtAb) are unable to clear an established infection, they have shown promise in providing protection against the contraction of HIV. However bNtAb have proven to be extremely difficult to generate by immunization. Marinieve Montero is studying the antigenicity and immunogenicity of the HIV-1 transmenbrane glycoprotein gp41, to which several bNtAb are directed. Her work will involve an exhaustive biochemical characterization of the gp41 protein presentation in the context of membranes, and the analysis of the bNtAb response generated after immunization of animals. The results from her study will improve the understanding of the biology of bNtAb production, and may be a valuable aid in the design of successful vaccine candidates and immunization methods.

The Development of Joint Attention within Parent-infant Interaction

The development of children’s thinking and successful participation in healthy social interaction depends on their ability to share attention with others. Called joint attention, this ability begins to emerge by a child’s first birthday and enables them to learn about people, language and ways of thinking. Infants in whom this developmental milestone is delayed are often from at-risk groups, such as low birth weight children. The delay is also associated with autism, Attention Deficit Hyperactivity Disorder and language impairment. By studying observable aspects of joint attention, Timothy Racine is testing whether the parent-child relationship affects its development. In particular, he aims to identify the age at which infants begin to direct others’ attention with pointing gestures, and whether parents with a supportive style of interacting have infants who point meaningfully at an earlier age. Results from the study could help in the education and training of parents on appropriate ways of establishing joint attention in both normally developing and at-risk infants.

Bioinformatic analysis of large-scale microarry data

Dr. Karsten Hokamp is already known for developing the PubCrawler service used worldwide to stay up to date with the medical literature database PubMed. Now he is working on a large-scale project comprising databases and tools to support genetic research into immune responses against viral and bacterial infections. As part of a major Genome Canada project, laboratories across Canada are studying genetic information on viral, bacterial and fungal infections that affect humans and animals. Researchers are using microarray technology to simultaneously examine thousands of genes. Karsten’s platform will be capable of storing and processing what may possibly be the largest set of microarray data ever generated in Canada. He will set up a system to collect and analyze the data, with capability of comparing genetic information from different organisms and species. This system will contribute to improved understanding of immune responses and will aid in developing new ways to prevent and treat infections in humans and animals. In addition, other institutions worldwide that are increasing production of microarray data could use this setup as a model.

Obesity in the community: a comparison of the differential distribution of body fat in four distinct populations

Being overweight or obese, especially around the stomach, dramatically increases one’s risk for health problems such as diabetes and heart disease. This is of great concern as the prevalence of obesity in Canada has steadily increased during the past 15 years. However, most of the research on obesity is based on populations with European origins; very little is known about the effects of being overweight in Aboriginal, Chinese and South Asian populations yet the rates of obesity in these populations are also increasing. Preliminary evidence suggests that at the same weight and stomach size, people of Aboriginal, Chinese or South Asian descent have a higher amount of body fat and greater risk for diabetes and heart disease compared to men and women of European descent. Therefore, using clinical targets for obesity developed from European populations may result in inappropriate screening for prevention of these diseases. Dr. Scott Lear’s research involves recruiting 200 people from each of the Aboriginal, Chinese, South Asian and European communities to study the relationship between cultural background, body fat distribution and risk for diabetes and heart disease. Each participant will undergo a scan for stomach fat, overall body fat and risk factors. By improving understanding about the implications of excess body fat in these under-studied populations, the research could lead to guidelines for identifying people at risk for chronic disease, and contribute to prevention strategies targeted to these populations.

The neuromuscular and sensorimotor basis of balance recovery

Falls and related injuries cause loss of independence, reduce quality of life, and increase mortality among elderly people. Fall-related injuries cost Canadians $3.6 billion in 1995. Consequently, reducing the incidence and severity of falls is an important health priority. Dawn Mackey is comparing young and elderly study participants to measure the variables that govern our ability to recover balance following unexpected movements. Maintaining a stable upright posture is essential to daily activities such as walking, turning and rising. However, postural stability declines as we age. Dawn will assess whether balance recovery depends on the strength and speed of muscle response, simultaneous contraction of front and back ankle muscles, where someone’s mental attention is focused, and the intactness and speed of sight and hearing. She hopes the research can be used to design exercise and rehabilitation programs to prevent falls among elderly people.

Novel enzyme inhibitors for the prevention of metastatic Cancer

Carbohydrate molecules exist on the surface of all cells in the body, and control the movement of various compounds-viruses, bacteria, hormones, toxins and drugs-in and out of cells. Metastasis-the spread of malignant cancer cells-is linked to changes in the carbohydrate molecules on the surface of cancer cells. A particular enzyme helps produce mutations in these carbohydrate molecules. In earlier research, Nag Kumar showed that some compounds from a plant (used to treat type-2 diabetes in the Ayurvedic medicine system) inhibit this enzyme. Now he is using this lead compound to develop potent inhibitors of this enzyme. His goal is to interfere with the synthesis of the large carbohydrate molecules on the cell surface, and use the new enzyme inhibitors to develop anti-cancer drugs that can prevent cancer.