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.
Year: 2004
Involvement of postsynaptic density proteins in synaptic specificity and spine formation
Neurons (brain cells) communicate with each other through a highly complex network of connections called synapses. Different types of synapses perform different roles. Abnormalities in these connections may be linked to psychiatric disorders including autism and schizophrenia. Joshua Levinson is investigating how neurons establish these contacts so consistently that virtually no errors occur despite their diversity. He is looking specifically at levels of particular proteins at the site of contact and how these levels affect the type of connection formed between neurons. He is also studying how these connections stabilize, which is critical for connections to form properly, and if proteins play a role in the stabilization process. The research could lead to a clearer understanding of the neurological abnormalities that underlie psychiatric diseases such as autism and schizophrenia, and contribute to more effective treatments.
Computational identification of genetic variation in gene regulatory networks
Our genes encode all the information that makes us human. The recent sequencing of the human genome, completed in 2003, identified all of the approximately 30,000 genes in human DNA. However, each person has variations in their genetic makeup that account for the diversity in their quality of life. A major focus of genetic research is studying the nature of genetic variation. Single nucleotide polymorphisms (SNPs) are variations in DNA sequences that are the most common molecular mechanisms of genetic variation. Studies show SNPs play a role in the development of various diseases, including depression, cancer, lupus and Alzheimer’s. Stephen Montgomery, who was part of the research team at Canada’s Michael Smith Genome Sciences Centre that sequenced the SARS virus, has been designing and building software to aid in identifying SNPs and other sources of genetic variation that regulate gene expression (the process by which genes are transcribed and translated into proteins). His work on further developing these tools and techniques could improve understanding of the molecular causes of genetic variation, which could suggest new therapies for combating diseases.
The role of antigen presenting cells in viral induced autoimmune diabetes
An autoimmune response occurs when the body’s immune system mounts an attack on its own organs or tissues. Type 1 diabetes, for example, results when immune cells destroy insulin-producing cells in the pancreas. Although genetic predisposition is a major factor, seemingly benign viral infections also may play a role in this disease. However, the mechanisms by which viral infections cause autoimmune disease remain unclear. Martin Richer is researching how viruses cause autoimmune type 1 diabetes. He is investigating the mechanisms by which the immune system is sensitized by exposure to a virus and mounts an attack on normal cells. Martin is also studying how this activity influences the development and progression of disease, and how the process can be regulated. The findings could improve understanding of how viral infections lead to autoimmune responses and diseases such as type 1 diabetes.
The roles of apoptosis and IGF-I in tendinosis of the rotator cuff
Physical activities involving repetitive strain can injure tendons, causing chronic pain and disability. Contrary to previous thinking, chronic overuse tendon injuries do not involve inflammation. Instead, these injuries primarily involve the breakdown and disarray of collagen, a structural protein that is the primary support for tendons as well as bone, cartilage and skin. Recent research associates chronic tendon injury with excessive apoptosis (programmed cell death) among tendon cells. Alexander Scott’s preliminary laboratory studies identified two stressful conditions that can cause the problem: repetitive mechanical strain and lack of oxygen. Now he is investigating the basic mechanisms of tendon degeneration, with the aim of discovering whether abnormal rates of cell death occur in real life models of tendon injury. Alexander is also testing whether IGF-1, a potent growth factor, can help tendons better recover from injury. The research could lead to new treatments for people who suffer from painful tendon injuries.
Nrf2-mediated activation of Phase II detoxification genes as a novel neuroprotective strategy for stroke
Stroke is the fourth leading cause of death in Canada. A number of factors contribute to nerve cell death during a stroke. One major cause is the accumulation of free radicals (oxygen molecules that take electrons from healthy cells in the process known as oxidation), which causes cellular damage. Compared to other brain cells, nerve cells are particularly susceptible to damage by free radicals. Damage to nerve tissues worsens over the hours or days following a stroke due to an imbalance between free radicals and the antioxidants that normally protect cells. Andy Shih is researching ways to increase antioxidant levels to maintain balance and prevent cellular damage during stroke. Andy is specifically examining the ability of the Nrf2 protein to launch the cell’s antioxidant defenses, remove free radicals and repair damage. This research could confirm if Nrf2 can promote neuronal survival after stroke, hopefully improving functional recovery. Interestingly, a number of molecules that can activate Nrf2 are found in cruciferous vegetables, such as broccoli. Diet-based therapies that favour Nrf2 activation could be effective and practical therapeutic approaches.
The effects of electroconvulsive therapy in an animal model of Parkinson's disease: mechanisms of a potential adjunct treatment
Parkinson’s disease is a progressive, neurodegenerative disorder that affects more than 100,000 Canadians. The disease involves the degeneration of nerve cells that produce dopamine, a neurotransmitter (chemical messenger) that transmits messages between cells. Insufficient dopamine interrupts the message flow, leading to loss of motor function. Various drugs are used to treat Parkinson’s, but they can cause debilitating side effects and become less effective after prolonged use. Patients with Parkinson’s disease often experience major depression. Electroconvulsive therapy (ECT), which is widely used to treat depression, appears to improve the motor symptoms of Parkinson’s as well. Elissa Strome is investigating whether ECT has beneficial effects in the brain regions associated with Parkinson’s disease. She aims to determine how ECT affects transmission of brain signals and improves motor symptoms. This research could reveal if ECT is an effective treatment for patients with Parkinson’s disease.
Motuporamine C: a novel compound to examine the intracellular pathways governing neuronal outgrowth
About 36,000 Canadians live with a spinal cord injury. Lifetime cost of treating these injuries range from $1.25 million to $25 million per person, depending on the level of injury. Following a spinal cord injury, the traumatized area of the body prevents nerve cells from regenerating. Kenneth To is studying how nerve cells move from the spinal cord to various locations in the body, and which proteins guide these cells to their final destination. Identifying the proteins responsible for nerve cell movement could enable regeneration of nerve cells after a spinal cord injury. As a long-term goal, Kenneth aims to identify new targets for promoting nerve cell regeneration following a spinal cord injury.
Natural killer cell lineage commitment
Natural killer (NK) cells are white blood cells that fight infection by killing a variety of virus-infected cells and tumours. NK cells can distinguish normal, healthy cells from unhealthy cells and kill only the latter. It’s also believed that NK cells help eliminate residual tumour cells following bone marrow transplant into leukemia patients. While the function of NK cells has been well-researched, less is known about how these cells develop. All blood cells arise from hematopoietic stem cells through a process called lineage commitment, in which stem cells differentiate into various types of cells. Linnea Veinotte aims to define that process for NK cells. In previous research funded by MSFHR, Linnea discovered that some NK cells express a gene specific to T cells: the T cell receptor gamma gene. Linnea is investigating T cell receptor gamma gene expression in NK cells and how it may help define the developmental pathway of NK cells. The findings could provide insights about how NK cells develop — crucial information given the important role of NK cells in the body’s immune response.
Role of Huntingtin phosphorylation by Akt in HD
Huntington’s disease (HD) is a fatal neurodegenerative disorder that usually begins in mid-life and causes progressive loss of motor control and mental capacity. One in 10,000 Canadians has this untreatable and devastating inherited disease. The HD gene produces the huntingtin protein, a protective molecule found in all regions of the human brain. However, when the HD gene mutates, it causes specific nerve cells to degenerate. Simon Warby aims to identify the factors that enable this location-specific and age-dependent degeneration in the brain. An important enzyme called Akt regulates the protective functions of huntingtin. Simon is investigating whether alterations in this enzyme and reduced levels of a molecule called BDNF (brain derived neurotrophic factor) turn off huntingtin’s protective functions. The research could contribute to therapies for reversing the degenerative process that characterize Huntington disease.