New routes to sialidase inhibitors: Synthesis, characterization, and evaluation of novel sialic acid derivatives

For many people, infection with the influenza virus results in several days of illness. Yet, each year, the virus is responsible for approximately one million deaths worldwide. Vaccines are the most common preventive treatment, but they only protect vaccinated individuals against those strains identified by the World Health Organization as being the most virulent in any given season. When a new strain of influenza appears against which humans have no immunity – as occurred with the Spanish flu pandemic of 1918 (which killed 20 million people worldwide), the Asian flu pandemic of 1957, and the Hong Kong flu pandemic of 1968 – the result is a pandemic that could infect and kill hundreds of millions of people worldwide. Better treatments and preventative measures to fight influenza infection are needed to counter this threat. There are currently two major anti-influenza drugs on the market that selectively inhibit a viral enzyme that is critical to spreading infection. While these drugs are effective, the influenza virus is resilient and by mutating can develop drug-resistant strains. Ivan Hemeon is researching the development of new anti-influenza compounds that have a much lower risk of generating resistant strains. Hopefully, people treated with these compounds would experience less severe symptoms and recover faster without the risk of harbouring resistant strains that could be passed on to others, particularly those made more vulnerable due to compromised immune systems.

The construct, structural and predictive validity of the Hare Psychopathy Checklist, Youth Version in adolescent females: Informing the assessment of risk for violence in girls

Aggressive and violent behaviour among female youth has emerged as a pressing social issue. Girls are entering the juvenile justice system for violent offenses at substantially higher rates than five or ten years ago. Unfortunately, our ability to gauge risk for violence among female youth is less than optimal, mainly because research has focused on identifying risk factors that predict violence and aggression in boys. Consequently, unique risk factors in girls may go undetected. Psychopathy is a powerful predictor of future violence in adult male prisoners, and is characterized by a callous disregard for others, a lack of empathy, and a propensity to highly impulsive and irresponsible behaviour. Despite the important role of psychopathy in violence risk prediction, little research has examined whether the construct of psychopathy applies to females, and virtually no studies have focused on female adolescents. Stephanie Penney is investigating how well psychopathy predicts future violence in girls compared to boys. Stephanie is examining how development, early socialization and environmental influences converge to create risk for females. This research will identify unique risk factors that predispose girls to aggressive and violent behaviour, and can be used to develop early intervention programs to reduce violence among high-risk girls.

Functional characterization of Bardet-Biedl proteins

Bardet-Biedl Syndrome (BBS) is a complex genetic disease that affects many different body parts, including the eyes, kidney and heart. Symptoms include blindness, obesity, diabetes, kidney dysfunction, congenital heart defects and extra fingers or toes. At least eight genes (BBS1 to BBS8) are linked to the syndrome. Recent studies suggest that defective cilia (short, hair-like projections that protrude from the cell surface and help clean out airways) may be the primary cause of the syndrome. Junchul Kim is investigating whether this defect causes Bardet-Biedl Syndrome. He is studying the role of proteins encoded by BBS genes to see if mutations in these genes affect different body parts during development. This research could provide insights into how the syndrome develops and potentially lead to new treatments for many common disorders, such as diabetes and obesity.

Bathing without a battle: organizational and physical environmental features associated with resident agitation during bathing on dementia special care units

Agitation in cognitively impaired individuals is one of the most difficult behaviours for nursing home staff to manage. Research indicates that between 40 percent and 73 percent of long-term care residents with dementia display disruptive behaviour during bathing. This behaviour, which causes distress and sometimes injury for both residents and staff, ranges from verbal and physical resistance, to hostile language, punches, hits and slaps. Both the organizational and physical environments of a long-term care facility are believed to influence resident agitation levels. However, most research on the bathing of individuals with dementia has focused on only one of these environments. Heather Cooke is examining the bathing policies, training of bath staff, staff assignment and physical features of bathing areas in all Dementia Special Care Units in B.C., to explore the role of such features in the occurrence of resident agitation during bathing. Findings from the study will be used to develop standards and best practices designed to reduce resident agitation and to guide health care planners in the appropriate distribution of funds for improving the care facility.

The identification and characterization of candidate Bardet-Biedl Syndrome genes and/or genes specifically involved in ciliary functions

Bardet-Biedl syndrome (BBS) is a complex genetic disease with symptoms that include obesity, blindness and kidney dysfunction. Although seven genes linked to the disease have been cloned, the molecular origin of the syndrome remains unclear. Using Caenorhabitis elegans (a tiny worm) as a model for BBS, Dr. Oliver Blacque’s previous research contributed to the finding that a primary cause of the disease is likely to be malfunctioning cilia, which are finger-like projections that naturally protrude from many human cells. Cilia malfunction has also been shown to cause other conditions including polycystic kidney disease and retinal degeneration. Dr. Blacque is now investigating how cilia operate at the molecular level. He is using tools of bioinformatics (management of biological information with computer technology) and genomics (study of genes) to identify proteins that operate exclusively in cilia and to investigate their functions. The research could improve understanding of the role of cilia in human disease and lead to the discovery of new proteins that cause Bardet-Biedl syndrome and other cilia-related diseases.

Hyperpolarization activated pacemaker channel regulation of cardiac automaticity and rhythm during postnatal development

Cardiac arrhythmias (an irregular heartbeat) can cause heart attacks and stroke or sudden death, especially in infants. Pacemaker cells in the heart beat spontaneously, unlike other heart cells, and set the heartbeat frequency. Dr. Jacob Ross is studying the role of a critical protein, the pacemaker channel, found in these cells, which causes them to spontaneously beat and may also regulate electrical activity in other areas of the heart. In particular, the pacemaker channel may regulate the ventricle, the heart’s main pumping chamber. Dr. Ross is examining the molecular and electrical properties of pacemaker channels and investigating how adrenaline-like substances affect these proteins in the ventricle. This research could provide a better understanding of basic cardiac function, which could improve prevention and treatment of cardiac arrhythmias.

Computational prediction and analysis of subcellular localization of bacterial proteins

Jennifer Gardy’s research is directed at predicting the location of proteins in disease-causing bacteria that could be targeted as potential vaccines or antibiotics. Jennifer developed PSORT-B, a software program that examines the biological features of proteins to predict where they most likely reside. It is the most precise software currently available for this purpose. Using data mining techniques that help establish relationships and identify patterns, Jennifer is fine-tuning the software to make it more accurate in predicting protein locations and functions. She is also developing modified versions of the program for specific groups of bacteria. Her aim is to make PSORT-B the leading software program for identifying vaccine and antibiotic targets.

Investigation of the effects of floor stiffness on risk of fall-related hip fractures

About 23,000 people fracture their hips in Canada each year, resulting in treatment costs of approximately $1 billion. Without improvements in prevention and given Canada’s aging population, hip fractures are expected to quadruple by 2041. Falls cause more than 90 percent of hip fractures. Fracture risk during a fall depends on the force of the impact on the femur (thigh bone). Andrew Laing is evaluating the potential of low stiffness flooring to reduce the risk of fall-related hip fractures in high-risk environments such as nursing homes and hospitals. In laboratory experiments, Andrew is testing whether reducing floor stiffness decreases force applied to a hip during a fall, and whether floor stiffness can be reduced without impairing balance. Findings could contribute to the design of flooring that reduces risk of hip fractures and provide insight into similar interventions to reduce wrist, spinal cord and head injuries.

Novel statistical methods for inference of associations between traits and SNP haplotypes in the presence of uncertain haplotype phase

A single gene can be solely responsible for certain genetic disorders. For example, only people who carry two defective copies of the CFTR gene develop cystic fibrosis. By contrast, complex genetic disorders such as cancer and diabetes likely involve a number of genes that increase susceptibility, and act in conjunction with lifestyle and environmental exposures to increase risk for developing disease. Most success in identifying single causative genes has been achieved by studying co-segregation of a trait with genomic regions in families. However, to tackle complex disorders, researchers have turned from family studies to population studies that investigate associations between a disease and variations in DNA sequences known as single nucleotide polymorphisms (SNPs). Blocks of SNPs, known as haplotypes, offer promise for identifying genes contributing to disease risk. For example, SNP haplotypes were used to help identify a predisposing gene for Crohn’s disease. The underlying idea is that similarity among haplotypes of affected individuals will lead to disease associations. Dr. Jinko Graham is developing improved biostatistical methods that account for haplotype uncertainty in analyzing these disease associations. The new techniques will eliminate inaccuracies associated with previous methods and could enable researchers to better evaluate genetic and environmental risks for conditions including diabetes, cancer and cardiovascular disease.

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.