Research Location: Simon Fraser University

Naturally occurring cellular components such as enzymes are often the only tools available to perform biological research, a limitation that slows the pace of research and hinders the search for cures to human disease. The situation is similar to having your car break down in the middle of the street and having to make repairs using parts scavenged from neighbouring automobiles. A proper toolbox would greatly decrease the time required to perform the repair. My research examines the potential functions of ribonucleic acid (RNA), a cellular component which is vital for the development and functioning of all living things. I am examining the ability of RNA to replicate itself, without the help of protein, because RNA may be capable of important metabolic functions that are currently performed by protein enzymes. I am developing in vitro (in the test tube) techniques to isolate new RNA catalytic molecules. Because these artificially manufactured catalysts perform specific functions, they can be used as tools for conducting medical research. Ultimately, I will examine whether artificial RNA sequences can interact with existing cellular components. Such experiments give us a better understanding of natural processes within cells, perhaps leading to potent new genetic therapies for the treatment of disease.

DNA and RNA (the genetic matter in the cells of all living organisms) have properties beyond their function as storehouses of genetic information. I am examining ways we can exploit these other properties to develop new biomedical applications to combat disease. For example, DNA has a slight tendency to conduct electricity. I am investigating how to harness this conductivity to generate sensors that can detect and monitor hormones, metabolites (substances essential to metabolism), toxins, enzymes, drugs, proteins and other molecules in the blood or other body fluids. DNA has potential as an electrical tool to manipulate products at the molecular level. A major interest of mine is based on the discovery that synthetic enzymes made out of DNA and RNA can sometimes function as efficiently as naturally occurring enzymes. Enzymes act as catalysts to accelerate chemical reactions and cellular processes in the body, such as breaking down food during the digestive process. With huge, synthetic DNA and RNA libraries available, we have endless opportunities to create enzymes that perform specific therapeutic functions. Ultimately, we hope to synthesize nucleic acid enzymes to help counteract cancers and viral infections.

My research lab uses fluorescence imaging technology combined with electrophysiological measurements to study problems with the transmission of information in the brain. Such problems are the foundation of numerous brain disorders including schizophrenia, depression and Parkinson’s disease. We need a thorough understanding of the brain’s communication process to understand and develop treatments for these disorders. Brain function depends on the activity of neuronal circuits, which are formed by thousands or millions of neurons (nerve cells) that communicate with each other at points of contact called synapses. Neurons communicate when the pre-synaptic neuron releases a chemical transmitter that diffuses across the synaptic space and binds to receptors on the post-synaptic (receiving) neuron. The receptors are often located on branches of the neuron called dendrites. My research examines the factors that control the amount of chemical transmitter released, and in particular, the regulation of release by calcium ions in pre-synaptic neurons. Transmitter release is stimulated by an influx of calcium into the pre-synaptic neuron. Calcium influx is controlled by changes in the electrical potential of the pre-synaptic neuron that regulate the opening and closing of the voltage sensitive “”gates”” of calcium permeable pores in the neuron’s surface. By changing calcium influx and accumulation in neurons, the strength of the synaptic connection can be varied to adapt to new conditions or tasks. Using fluorescent dyes that are sensitive to calcium, we monitor calcium in pre-synaptic neurons at the same time that we measure synaptic transmission electrically. Our laboratory has the unique capability to make these measurements in an intact living mammalian brain. We are investigating how activity in the pre-synaptic neuron and substances such as dopamine or serotonin control transmitter release by their effects on calcium, and the biochemical machinery that release transmitter in response to calcium. We also are studying how the signal reception at the post-synaptic neuron is regulated by electrical properties of the dendrites.