Research Project
9142166
? DESCRIPTION (provided by applicant): The nematode, Caenorhabditis elegans, is a powerful experimental system that is widely used as a model for a large number of high-impact medical conditions, from aging and metabolic disorders to neurodegenerative diseases. The strength of this microscopic worm as a medical model derives from the extensive genetic homology between nematodes and humans, together with the many powerful tools that are available to manipulate C. elegans genes. Another key advantage of C. elegans is that medical dysfunction is manifested by changes even in simple behaviors such as locomotion and feeding, and the mitigation of these changes has been used successfully to test potential new treatments. At present, however, feeding behavior is quantified by a human observer who uses a microscope to count swallowing events (peristaltic pumps of the pharynx) by eye. This method is inaccurate because swallowing occurs at up to five times per second (5 Hz), which is far too rapid for accurate visual counting. Furthermore, only brief periods (e.g., 30 sec) of swallowing are typically counted because the method is both time-consuming and tedious. Many disease models and gene mutations cause pharyngeal pumping defects in C. elegans, but the status quo quantification method is inadequate for capitalizing on the information-rich data on physiological status provided by feeding behavior. To address this limitation, NemaMetrix Inc. developed an award-winning, patent-pending microfluidic device that counts swallowing events electrically, in much the same way as a bedside heart monitor counts heartbeats. The new platform dramatically increases counting accuracy, the number of worms that can be analyzed, and the number of events counted per worm, thereby enhancing efficiency and statistical power. The overarching goal of this proposal is to develop a fully integrated, turn-key system that will allow minimally-trained laboratory personnel to quantify feeding behavior by electrical measures for the first time. The Specific Aims are to develop easy-to-use software for making and analyzing electrical recordings of feeding behavior using NemaMetrix technology. The proposed recording system promises to accelerate basic research into the cellular and molecular mechanisms of human disease, and provide a novel test bed for academic and industrial research that could lead to new treatments for high-impact disorders.
