The sophisticated approaches of genomics are increasingly being used to analyze the majority of the genetic material contained within cells. The tools of genomics have catalyzed remarkable developments in health and disease research. These tools continue to evolve at a rapid pace, making possible additional health research opportunities that are increasingly comprehensive. Dr. Marco Marra is Director of the British Columbia Cancer Agency Genome Sciences Centre. Dr. Marra was funded as an MSFHR Scholar in 2001, with a specific focus of using genomics to comprehensively search for genes that play roles in cancer. In 2003, Dr. Marra also distinguished himself as leading the team that cracked the genetic code for SARS. In addition to his continuing work in cancer genomics, Dr. Marra is also working to identify and analyze DNA mutations correlated with, or causing, mental retardation. A consistent theme in Dr. Marraâs research is the identification and analysis of new genes and new gene products to determine their potential for use as new therapies or vaccines to combat cancer, infectious diseases, and other disorders.
Year: 2006
Applications of bioorganic chemistry to medicine
Chemistry plays a central role in uncovering the mysteries of biology, and in the generation of new ways to approach diagnostics and disease therapies. An exciting area for health research is in the development of synthetic chemistry â the creation of âman madeâ molecules that contain properties that regular DNA does not possess. This merging of chemistry and biology towards medically relevant goalsâsuch as developing antiviral compounds or radiopharmaceuticals for diagnostics or treatmentârepresent a powerful combination. Dr. David Perrinâs work involves the creation of synthetic DNA and peptides that may be useful in recognizing, imaging and ultimately interfering with or halting disease processes. He generates new molecules based on amino acids and nucleic acids, which have potential for disrupting RNA activity in diseases such as cancer or HIV. In addition to researching the use of synthetic DNA in disease therapies, Dr. Perrin has developed a new class of PET imaging (Positron Emission Topography) probes for the efficient radiolabelling of biomolecules. These biomolecules have the potential to image and possibly eradicate cancer directly or permit more precise monitoring of its progression in conjunction with other targeted therapies.
The role of RNA in the evolution of life
One of the fundamental issues facing biology is the question of our origins. Despite the fact that time and evolution have erased much information about early life on earth, a number of fascinating clues remain within cells that have led to the proposal of an âRNA worldâ hypothesis â the premise that RNA (ribonucleic acid) was once the dominant biological catalyst, capable of important metabolic functions that are currently performed by protein enzymes. Dr. Peter Unrau is exploring the chemical versatility and evolutionary potential of RNA. He has been examining the ability of RNA to replicate independent of protein. Along with his chemical interests in RNA, he is also exploring the processing of RNA by eukaryotes (cells with a distinct membrane-bound nucleus) and studying the interaction of small RNA processing and viral replication in plants and humans.
Targeting the beta cell for Diabetes therapy
In healthy people, blood glucose levels are tightly controlled by insulin, a hormone produced by beta cells in the pancreas. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas to lower the glucose level. In type 1 diabetes, beta cells are destroyed by oneâs own immune system. In type 2 diabetes, insulin secretion from beta cells is insufficient and beta cells are gradually lost due to the toxic effects of fats, high glucose levels and build-up of toxic amyloid deposits in the pancreas. Dr. Verchereâs research is focused on understanding how beta cells normally function in health, and what goes wrong in diabetes. He is investigating why toxic islet amyloid deposits form and how they kill beta cells, as well as how immune cells kill beta cells in type 1 diabetes. He is also looking at ways to protect transplanted beta cells from immune destruction. His long-term goal is to develop novel therapies that enhance beta cell survival and function in type 1 and type 2 diabetes.
Characterization of oligodendrocyte abnormalities in schizophrenia
Schizophrenia is a severe psychiatric illness affecting approximately one per cent of Canadians. While the causes are not yet fully understood, it is thought that the symptoms of this disorder may arise from abnormalities in nerve fibre connections between different brain regions. Mounting evidence suggests that a contributing factor may be abnormalities in myelin, the fatty insulating substance that surrounds nerve fibres and speeds up the transmission of nerve impulses. Studies have shown reduced density of oligodendrocytes, the brain cells that produce myelin, and altered expression of several proteins found specifically in myelinâsuggesting a possible source for impaired transmission of nerve impulses between brain regions. Through a series of investigations Dr. Clare Beasley is examining the role of oligodendrocytes in schizophrenia. She will characterize oligodendrocyte alterations in the brain in schizophrenia and examine their relationship with myelin proteins and lipids. By better understanding the connection between abnormalities in these myelin-producing cells and the symptoms of schizophrenia, she hopes to shed light on the cause of this devastating disorder.
Rostrolateral prefrontal cortex modulation using real-time fMRI feedback training in healthy volunteers and depressed patients
Depression is a common mental disorder characterized by sadness, low energy, feelings of guilt and low self-worth. Even after patients recover from a major episode of depression, they remain vulnerable to subsequent depression relapse. Such depression relapse can be triggered by a relatively mild experience of sadness, during which depression vulnerability expresses itself through reduced metacognitive awareness: the awareness of oneâs own thought processes. Neuroimaging studies suggest that increased activation within the brainâs lateral prefrontal cortexâthe same region linked to metacognitive awarenessâis a positive result of treatment for depression, and that consistent activation may reduce the risk of depressive relapse. Dr. Kalina Christoff is researching whether patients who are prone to depression can prevent relapse by learning how to better control their brain activity within this region. She is examining whether real-time feedback from functional magnetic resonance imaging (fMRI) can help patients learn to consciously modulate their brain activity and prevent or reduce relapse.
Neuromagnetic responses related to the development of orthographic perception
As normal hearing and sighted children learn to read, they gain knowledge of associations between letters or words and their related sounds. Particular brain regions and processes are implicated in readingâreflected by measurable changes in brain activityâwhich develop as children progressively gain reading ability. By recording the magnetic fields produced by the brain, Dr. Anthony Herdman is identifying the changes that occur in brain activities when children begin to recognize letters. He is also investigating what happens in childrenâs brains when they combine sight and sound in order to learn letter-sound and word-sound pairs. His goal is to gain a better understanding of the changes in cerebral activity within in the developing brain over the course reading acquisition.
Selective attention systems and their integration in children with Autism
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.
Abnormal brain development in premature newborns
Many children who have been born prematurely experience long-term cognitive, visual and motor deficits. A number of interrelated factors that commonly follow preterm birth are believed to contribute to neurodevelopmental impairment, including newborn illness and exposure to medications, abnormal brain development in the months following birth, and a characteristic type of brain injury known as white matter injury. Currently, there is little research regarding how white matter injury and abnormal brain development lead to impaired motor and cognitive function. Dr. Steven Miller is researching brain development and injury in premature babies to understand how such injuries occur and why specific brain regions are affected. Using magnetic resonance imaging (MRI) techniques, Dr. Miller is measuring brain development and white matter injury in premature newborns shortly after birth and then again when the newborns reach term-equivalent age. Subsequent tests measuring gross and fine motor skills, language and cognition will be conducted at 18 and 36 months of age to evaluate neurodevelopmental outcome. The results of this study will provide a better understanding of the factors impacting brain growth and injury in newborns, and lead to improvements in preventing or treating brain injury in this population. Dr. Millerâs research group also studies brain development and white matter injury in other groups of newborns at high risk of neurodevelopmental impairments, such as those with heart birth defects.
Functional dysconnectivity of hippocampo-prefrontal neural systems in Schizophrenia
Schizophrenia is a brain disease that affects one per cent of Canadians â more than 300,000 people â causing hallucinations and disordered thought . Early intervention and prevention of relapse are key to minimizing the impact of schizophrenia on individuals and society, and an understanding of the brain changes that lead to first episode and relapse are important for achieving preventive care. Major aspects of schizophrenia include memory dysfunction and reality distortion, such as hallucinations and delusions. The brain systems that underlie these symptoms appear to involve neural systems in the hippocampo-prefrontal regions of the brain. While these neural systems exhibit a high degree of connectivity in healthy subjects, it is thought that dysconnectivity may be an underlying cause for schizophrenic symptoms. To demonstrate the role of impaired neural connectivity in schizophrenia, Dr. Todd Woodward is conducting neuroimaging studies to identify and characterize two hippocampal-prefrontal neural systems associated with schizophrenia. This functional and physiological understanding of the disease may allow for better prediction of first episode and relapse, in order to maximize early intervention.