Research Location: University of British Columbia

Normal nervous system function requires the generation of an enormous diversity of neurons during development. Differences in the identity and function of neurons depend upon differences in the repertoire of genes that the neuron expresses. Differential expression of these genes is controlled by intrinsic factors—the complement of transcription factors that exist within the neurons— and by extrinsic factors, signals secreted by other cells. Alterations in either of these factors have been implicated in many developmental, psychiatric and degenerative diseases. Dr. Douglas Allan is investigating how these intrinsic and extrinsic signals interact in neurons to selectively turn on the expression of different repertoires of genes in different neurons, so that the neurons attain their appropriate form and function. He is using the fruit fly, Drosophila melanogaster, as a model organism to study these mechanisms, because of the battery of powerful molecular genetic experimental tools available in this organism. Since the basic mechanisms of neuronal development are shared by fruit flies and humans, his work is relevant to understanding how human neurons develop and how disruption of these signals can cause disease.

Synapses of the central nervous system—junctions across which a nerve impulse passes from neuron to neuron—are highly-specialized regions of cell-to-cell contact. Deficiencies in synaptic function are central in many psychiatric and neurodegenerative diseases such as schizophrenia, Alzheimer’s, Parkinson’s and Huntington’s disease. Cell adhesion molecules, localized at synapses, are believed to have an important role in the regulation of synapse formation, maintenance and function. Dr. Shernaz Bamji has previously shown that cadherin and beta-catenin adhesion complexes act to recruit and tether synaptic vesicles to presynaptic compartments, and that transient disruptions of these adhesion complexes are important for the sprouting of new synapses. She is now further investigating the cellular and molecular mechanisms by which synaptic cell adhesion molecules regulate the formation, stability, and elimination of CNS synapses. . Understanding the underpinnings of these mechanisms may lead to the identification of new targets for therapeutic intervention in psychiatric and neurodegenerative diseases.

Transplantation of pancreatic islets has proven to be effective in controlling blood glucose levels in subjects with type 1 diabetes. The results of this procedure have demonstrated the potential to treat diabetes by transplanting as little as a teaspoon of insulin-producing cells into a diabetic patient. However, the promise of this procedure is currently restricted by two major challenges: transplantation is dependent upon the availability of tissue from recently deceased individuals; it also requires the use of chronic immunosuppression in the recipient, which carries the risk of side effects. Dr. Timothy Kieffer is investigating a variety of approaches to achieve the results of islet transplantation without relying on donor tissue. Ideally, he hopes to develop a therapy that uses the patient’s own cells and stimulates either the regrowth of insulin-producing beta cells, or the generation of new cells from adult stem cells. His team is also looking at ways to genetically modify the body’s gut cells to produce insulin or other anti-diabetic factors automatically in response to eating a meal.

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 – the creation of “man made” molecules that contain properties that regular DNA does not possess. This merging of chemistry and biology towards medically relevant goals—such as developing antiviral compounds or radiopharmaceuticals for diagnostics or treatment—represent a powerful combination. Dr. David Perrin’s 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.