Infection with the Human Immunodeficiency Virus type 1 (HIV-1) triggers a strong immune response in the body, which produces antibodies when it encounters the virus. However, the majority of antibodies naturally produced by the immune system are non-neutralizing, meaning they are unable to provide protection from the virus, or to prevent the eventual onset of AIDS. Alfredo Menendez is contributing to the search for an effective vaccine that would increase the body’s production of neutralizing antibodies. He has isolated unique peptides whose molecular structures closely mimic specific neutralizing sites on the surface of the virus. Alfredo is fine tuning these mimics to develop immunogens (substances that prompt a response from the immune system). He is investigating whether use of the peptides in a vaccine prompts a focused, strong and protective immune reaction that boosts the production of HIV-neutralizing antibodies.
Research Location: Simon Fraser University
Structural analysis of the bacterial Sec-dependent protein secretion system
Cells have compartments separated by membranes. Many proteins are made in one compartment but actually function in another. The ability of proteins to travel across membranes within cells is essential to cell life. Malfunctions in this process can lead to a variety of inherited and autoimmune diseases in humans. Dr. Mark Paetzel’s research focuses on the mechanisms by which proteins travel across cell membranes, a process called protein targeting and translocation. Using the technique of X-ray crystallography, Dr. Paetzel is uncovering the three-dimensional structures of the protein complexes that make up the molecular machines involved in bacterial protein targeting and translocation. A better understanding of the functions and mechanisms of these protein complexes may yield insights about how the process works in human cells. In addition, learning how the process differs between bacteria and human cells could lead to a novel class of antibiotics that can shut down protein targeting and translocation activities in bacteria, but leaves human cells unaffected.
Health status and health care utilization among mid-life Chinese, South Asian, and British Canadians in the lower mainland: An examination of socio-economic, immigration, and cultural dimensions
Dr. Karen Kobayashi has long been interested in how ethnicity affects aging and health. In her current research, Karen is comparing the health of Chinese and South Asian adults—the fastest growing ethnic groups in the Lower Mainland—with Canadians of British origin. She is examining differences in health status and use of health services among middle age Canadians to determine the factors that may promote or impede healthy aging. The research involves interviewing participants to determine how differences in such variables as education, income, time since immigration, English language ability, religious affiliation, and adherence to traditional values affect their health status and the way they use health services. She anticipates the research will reveal differences between and within cultural groups. For example, the way foreign-born and Canadian-born adults access health services may vary within each population group. The way new immigrants use health services may also vary from people who have lived in Canada for 10 years or more. This information could be used to predict health care needs among the groups and improve access to health services for these populations as they age.
Synthesis and Evaluation of a Novel Class of Glycosidase Inhibitors for the Treatment of Type-2 Diabetes
Ahmad Ghavami’s PhD research involved a rare South Asian plant containing compounds that could be helpful in the treatment of type 2 diabetes. The Salacia reticulata climbing plant has been used for centuries in treatment of diabetes in Sri Lanka and India. Researchers have isolated compounds from the plant and demonstrated their effectiveness in inhibiting glycosidases, the enzymes that break down starch into smaller sugars, and finally into glucose. Using the compounds to inhibit these enzymes in people with type 2 diabetes could lower blood glucose concentration, which is critical in treatment of the disease. Ahmad and his colleagues designed a method to synthetically produce the plant’s compounds, together with the next generation analogues, and they tested the inhibitory effects on a wide range of enzymes. More importantly, in vivo studies with rats have shown effective control of blood glucose levels with use of Ghavami’s compounds. Results from the study confirm the effectiveness of the method for designing and synthesizing a new class of molecules that function as glycosidase inhibitors, which can control the breakdown of carbohydrates. These findings were patented, with Ahmad listed as part inventor, and were responsible for securing venture capital and the formation of a spin-off company, Mimos Therapeutics, Inc.
The evaluation of human telemanipulation under spatial misalignment conditions in minimally invasive surgery
Bin Zheng isn’t daunted by challenge. At 16, he entered medical school. By age 27, he was a specialist in pediatric orthopedic surgery at a hospital affiliated with China Medical University. Now he is in Canada focusing his efforts on research to refine and improve the technology used in minimally invasive surgery. Because of more rapid healing and other benefits, this surgical practice is increasingly common. Zheng is working on an issue, which he has experienced first-hand, that occurs when images projected by the tiny cameras inserted into the body to guide the surgeon’s action do not align exactly with the area of the body on which the surgeon is working. His immediate goals are to assess the effects of this misalignment on surgical performance and patient outcome and also look for ways of improving the technology. In the long term, Zheng hopes to use these findings in the development of a systematic approach (scientific methodology) that can be applied to the evaluation of any new health technology.
Role of Membrane Binding in Regulation of the Activators of Ras
Dr. Joanne Johnson’s research examines events at the molecular level that ultimately lead to cell growth. Among the events is activation of cell surface receptors by ligand molecules, which leads to generation of specialized lipids in the cell membrane. These lipids act as signals to promote membrane binding and activation of proteins. Johnson is assessing the role of Diacylglycerol (DAG), and two newly identified proteins, RasGRP and CalDAG1. Johnson is specifically investigating how DAG and other lipids influence membrane binding and activity of RasGRP and CalDAG1, which function to activate the Ras protein, a critical switch in the control of cell growth. Knowledge of this process may lead to development of specific inhibitor drugs controlling cell growth and defending against tumours.
The effects of Sexualized Images and Stress on Body Image and Dieting: An Evolutionary Perspective
Why are so many women preoccupied with being thin? And why does this pre-occupation lead to eating disorders in certain women? Dr. Catherine Salmon is addressing these questions in her research by exploring the theory that pre-occupation for thinness and dieting could be part of an ancestral practice of exercising control over reproduction. Research has shown that females facing social or ecological conditions that are unfavourable for childbearing can sometimes delay reproduction until the situation improves. One way of doing this has been by reducing body fat to suppress ovulation. Salmon is exploring the notion that in modern society, women continuously experience cues indicating a poor environment for reproduction, such as high levels of competition between females and stressful sexual attention. Salmon hopes that learning more about these factors underlying body image and dieting will lead to more appropriate interventions for eating disorders.
Prevention of falls and hip fractures in the elderly through biomechanics
Falls are the number one cause of injury-related deaths and hospitalizations in Canada. Among the elderly, falls account for 84 per cent of all injuries and about 23,000 hip fractures annually. Reducing the frequency and severity of these injuries is a critical national health priority, and one that my research team is approaching from several angles. In one approach, we are using laboratory experiments and mathematical modeling to study age-related changes in posture and balance along with strategies for avoiding injury in the event of a fall. In another approach, we are determining how movement patterns and risk for falls are affected by physiological factors, such as muscle strength and vision, and by behavioural factors, such as risk-taking tendencies. On the applied side, the team is working to develop devices such as hip pads, compliant floors and exercise programs to help prevent fractures. This combination of basic and applied efforts should lead to the development of innovative and effective techniques to prevent falls and fall-related fractures in the elderly.
Evolution of microbial virulence
There is currently a poor understanding of how a relatively harmless microbe can evolve into one that causes disease. However, analyzing microbial DNA indicates that these bacteria may exchange their DNA with one another, essentially sharing genes that cause disease. Some microbes have evolved into disease-producing organisms relatively recently, making them good models for examining how bacteria results in disease. That’s because we are more likely to relate genetic changes in bacteria to those that cause virulent disease when the changes are more recent. My team is conducting laboratory and computer research to analyze the role gene exchange plays in the development of disease-causing microbes, and to characterize the evolution of recent disease-causing microbes. Understanding how benign bacteria evolved into virulent disease-causing bacteria will increase knowledge of how bacteria cause disease and lead to genuinely new therapeutics and prophylactics to combat current disease-causing microbes, and hopefully help prevent new ones from emerging in the future.
Molecular chaperones and cellular protein folding
I am studying protein folding, a poorly understood but fundamental cellular process by which proteins made in cells fold to attain their correct three-dimensional structures (shapes) and become active. When proteins in a cell do not become active, the result is abnormal function, which often leads to disease. Amino acids are the basic component of proteins, with hundreds of amino acids in each protein. The sequence of amino acids in proteins dictates how a protein folds into its proper shape and achieves its specific function. In some instances, proteins called molecular chaperones have been shown to help newly-made proteins fold properly. My research focuses on understanding how molecular chaperones function at the biochemical and cellular levels, and determining what goes wrong when certain proteins don’t fold properly. For example, one protein called von Hippel-Lindau relies on a particular molecular chaperone to fold correctly. The protein’s loss of function is often caused by protein misfolding, and leads to the major cause of renal cancer. Other diseases, such as Huntington’s and Alzheimer’s, are also associated with the improper folding of proteins. My basic biomedical work on molecular chaperones helps us understand a fundamental process (protein folding) required for good health. Ultimately, such studies may also provide valuable clues regarding how to tackle some diseases that arise from protein misfolding.