Autism — a neurological disorder characterized by impaired communication and social interaction — is a severe and pervasive developmental disorder that usually appears in the first three years of a child’s life. Children and adults with autism have varying levels of difficulty with social interaction and communication. Early predictors of autism include the inability to notice and make meaning of social cues such as eyes and faces, while displaying an intense focus and attention to seemingly irrelevant, non-social objects such as watches or cars. These attentional disturbances are thought to play a key role in the development of perceptual abnormalitities, hindering social and emotional competence.
Dr. Grace Iarocci is investigating attentional disturbances in children with autism, Employing a series of computer tasks, she is assessing how the children’s orientation and selection attention processes are coordinated and integrated across vision and hearing. This innovative approach focuses on providing comprehensive and precise assessments of the efficiency of each of the processes of attention, as well as insight into the complexity of the organization and function of theses processes.
Dr. Iarocci is using the information gathered from this research to develop interventions that tackle the early markers underlying the behavioural symptoms of autism.
Individuals with a major mental disorder are at heightened risk of committing acts of violence, being victimized by others, and harming themselves. These adverse outcomes – and the factors that contribute or mitigate them – are known to be interconnected. However, there hasn’t been a coordinated research platform that addresses all three outcomes together and identifies how different risk and protective factors affect each of these outcomes individually, and in combination, over time.
This team will link together researchers across BC and around the world to identify the most important dynamic risk and protective factors for violence, and determine the best techniques to measure and analyze their change over time. Because many individuals with a major mental disorder also have problems related to substance use, the team will also assess the relationship between mental health, substance use and violence.
Cilia are slender appendages that protrude from most cells and tissues in humans. The motile forms produce whip-like motions, while the non-motile (known as “primary”) forms act as antennae, detecting chemical and physical changes in their environment. Both forms of cilia are critical to human health. For example, motile cilia propel sperm in males, and move debris in respiratory airways. Primary cilia are implicated in sensory processes such as vision, sense of smell and hearing. Defects in the forms or functions of cilia can cause a wide range of human ailments, including kidney and heart disease, obesity and diabetes, and sensory impairments such as blindness. Using bioinformatics, genetics, cell biology, biochemistry and genomics approaches, Dr. Michel Leroux is studying previously unknown components of cilia and characterizing them in the nematode C. Elegans and in human tissue culture cells. He is also working to identifying genes associated with the many ciliary disorders in humans, including some associated with obesity and cystic kidney disorders. By providing fundamental insights into the form and functions of cilia, Dr. Leroux’s studies may uncover new potential targets for therapy in a wide range of human diseases.
Sequencing the human genome has led to the realization that a relatively small number of genes can give rise to an enormously complex living organism. This can be explained by the fact that proteins can be modified after their initial assembly to have multiple functions in multiple locations in the co-ordination of cell growth and function. One such modification called O-GlcNAc has been shown to be involved in many cellular processes, however, its precise function has not yet been determined. Malfunctions in the regulation of O-GIcNAc-modified proteins have been implicated in such diverse diseases as diabetes, Alzheimer’s, Parkinson’s, and a variety of cancers. For example, diabetic patients have been found to have elevated O-GlcNAc levels, although it is not clear whether these high levels are a cause or an effect of diabetes. Using techniques including mass spectrometry, chemical synthesis and mouse models, Matthew Macauley’s goal is to develop a method for identifying proteins modified by O-GlcNAc. This will give valuable insights into how this modification process affects normal cell function and may provide new knowledge about its precise role (i.e. is it a cause or an effect) in diabetes. In turn, such knowledge may contribute to the development of more effective preventive and treatment strategies.
The molecular mechanisms that ensure proper chromosome segregation during the division of cells are of fundamental importance to maintaining the integrity of the genome (genomic stability). In humans, genomic instabilities arising from chromosome instabilities (CIN) or missegregation are known to be implicated in the development of certain types of cancer. Mutations in genes that cause genomic instability are now recognized as being important predisposing conditions that contribute to the initiation and progression of cancer. Using budding yeast as a model, Kirk McManus hopes to identify both the non-essential and essential genes of yeast regulating CIN for comparison with mammalian cells to determine any cross-species candidate genes that contribute to genome instability. A better understanding of the genetic basis of CIN in model organisms will provide candidate genes for those CIN genes mutated in cancer. The results of this research will be directly relevant to an understanding of cancer mechanisms, and may be useful in developing strategies for cancer therapy and for sub-classification of tumors based on their CIN mutational spectrum.
Vertebral fractures in the spine are the most common type of fractures resulting from osteoporosis. These fractures cause back pain, impair physical function, reduce quality of life, increase mortality, and result in massive hospital and continuing care costs. After one vertebral fracture, the risk of a second vertebral fracture within 12 months increases fourfold. Most vertebral fractures result from a backwards fall. Dr. Meena Sran is conducting the first study to examine the forces that impact the spine during a typical backwards fall, and ways to reduce this load. Meena is investigating three promising techniques for preventing vertebral fractures during falls: having high risk fallers wear padded, shock-absorbing protective garments; installing floors that are less stiff; and using safe-landing techniques. The research could contribute new strategies to prevent vertebral fractures.
Rates of violence among adolescent girls in Canada and the US have increased over the last decade. As girls move into adulthood, aggressive behavior has been linked to a number of negative physical, social and psychological outcomes. High-risk girls account for rising costs in health care, juvenile justice and social service systems, but little research has focused on gender-specific responses to the problem of girls’ aggression. Adult and male risk assessment models are used with girls, without evidence that these tools are applicable or effective. Dr. Candice Odgers is mapping girls’ developmental trajectories across adolescence and early adulthood to identify the key risk and protective factors related to girls’ aggression. In particular, Candice is examining the impact of maltreatment and victimization on predicting aggressive behavior among high-risk girls. She is also working with leading genetic scholars to investigate how these environmental risks interact with genetic risk to influence disruptive or aggressive behaviour. This research examines the interplay of nature and nurture in the development of aggression and should lead to more effective, and gender sensitive, screening and treatment procedures for girls.
Violent crime is a devastating social problem that affects the physical and mental health of victims, and has significant economic costs. Aggressive and violent behaviour among adolescents is particularly disturbing. Although adolescents who commit violent crimes are often incarcerated, placement in an institution does not reduce violent acts committed after release. A subset of aggressive adolescents demonstrates antisocial traits such as callousness, a lack of empathy, and a propensity for engaging in diverse, and at times severe, violent acts. These traits have been called “”psychopathic,”” because they appear to be an early version of adult psychopathy. These adolescents are at higher risk for continuing violent behaviour well into adulthood. While some research has examined biological causes, the family environment has been ignored, even though the family plays an important role in children’s development of empathy and social behaviour. Rosalind Catchpole is studying aggressive adolescents’ styles of relating to their caregivers and empathy levels. Her research will identify the risks and protective factors related to adolescent violence, and help improve intervention programs for aggressive adolescents.
Since the emergence of the population health field in the early 1990s, evidence has mounted demonstrating that health is more than simply a product of health care, biology and lifestyle. Indeed, population health outcomes are influenced by a multitude of factors, including employment, income, education, social supports, physical environment and early childhood development. Taken together, the social determinants of health (SDOH) provide a useful model for understanding the complexity underlying population health inequalities, and for formulating policy responses to address such inequalities. Despite relatively widespread acceptance of this model within academic and health policy circles, there are tremendous barriers to developing public policies and services designed to address health inequalities. These barriers include resistance to inter-sectoral collaboration within federal and provincial governments, as well as inadequate resources for inter-agency collaboration between community-based service providers. Patricia Collins is exploring awareness and application of the SDOH model among municipal politicians and community-based service providers, to determine if awareness translates into action to improve health outcomes. She is also exploring how print media present broader notions of health and well being, such as the social determinants of health, to the public. Patricia’s research will identify where more information on the SDOH model is needed, and how the model can be used to alleviate health inequalities in the GVRD.
Cell shape and cell movement play vital roles in organ formation and the sculpting of body shape in the development of multicellular organisms. The Rho family of small GTPases are key regulators of cell shape and cell movement through their participation in signaling pathways involved in a variety of cell processes. These proteins function as “molecular switches”, with the ability to alternate between active and inactive states. Malfunction of these switching mechanisms has been implicated in a variety of disorders including cancer, and a number of inherited conditions such as X-linked mental retardation and faciogenital dysplasia (Aarskog syndrome). These proteins have also been shown to be key regulators in wound healing. The p21-activated kinases (Paks) are proteins that have been shown to alter activity of the Rho GTPases Cdc42 and Rac, and are linked to the regulation of the actin cytoskeleton. Previous studies have demonstrated Pak’s function in the establishment of cell shape and movement via regulation of the actin cytoskeleton. However, the exact nature of Pak within the signaling cascade remains unclear. Ryan Conder’s recent studies have suggested a role for Pak in either the establishment or maintenance of specific membrane surfaces of a cell that are required for tumor suppressor proteins to position themselves properly. Using Drosophila (fruit fly) developmental processes as a model system, Ryan is studying the proteins involved in these signaling networks and establishing the mechanisms by which these developmental processes are regulated. He hopes that what he learns about these signaling pathways in Drosophila will shed light on their roles in human development and disease.
