Research in the Lockery Lab spans the spectrum from basic research into fundamental principles of neuronal function to translation research into neglected tropical diseases, aging and neurodegeneration.
Basic researchWe seek to understand the neuronal basis of behavior in the nematode worm Caenorhabditis elegans. C. elegans has a small nervous system (302 neurons) whose neurons and connectivity pattern have been completely characterized, providing a unique opportunity to trace the causes of behavior from sensation to action. This work is significant because it is likely to lead to universal principles of neural computation. Focusing on spatial orientation behaviors (esp. chemotaxis) and decision making, the lab's research integrates multiple levels of analysis, from genes to neurons, neurons to networks, and networks to behavior. Eight distinct approaches are brought to bear on the problem: electrophysiology, calcium imaging, optogenetics, microfluidics, quantitative behavioral analysis, laser ablations, and mathematical modeling. Through these efforts, we have identified the mechanism by which C. elegans computes the time derivative of chemosensory input, and the genetic basis of functional asymmetries in a bilaterally symmetrical nervous system. Other work includes development of a stochastic neural network model or random search behavior that correctly predicts the functional connectivity of identified neurons in C. elegans, and the effects of drugs of abuse on economic decision making. Many of these findings have required the development of new techniques and approaches, including the first methods for electrophysiological recordings from C. elegans neurons and for high-resolution calcium imaging in intact, freely moving worms engaged in natural behaviors. This work is funded by the National Institutes of Mental Health.
Our translational research concerns the development and commercialization of microfluidic devices for making electrophysiological recordings from C. elegans and parasitic nematodes. A microfluidic device (a.k.a "chip") can be thought of as a miniature plumbing system in which it is possible to precisely control and manipulate fluids that are constrained within small networks of channels, typically sub-millimeter in cross-sectional scale. Importantly, these devices can also be used to manipulate microorganisms such as nematodes. One of our major contributions to the field has been the demonstration that such devices can be adapted for recording electrical signals emitted by nematodes. We have further shown that these recordings can be used in drug development studies to perform initial screens for biological activity of novel compounds, and to discover the mode of action of these compounds. We foresee three main areas of application for these devices: anti-nematode drugs called anthelmintics, drugs for treatment of neuro- and neuromuscular degenerative diseases, and drugs for the amelioration of the effects of aging. The anthelmintic projects have important world-health implications, as more the 2 billion people carry nematode infections. This work is funded by the National Institutes of Health, the Oregon Nano and Microtechnologies Institute, and the Bill and Melinda Gates Foundation. The technology is being commercialized by NemaMetrix, Inc, a University of Oregon spin-out company (nemametrix.com).