Wednesday, April 2, 2025
4/2/2025
Advancing Human Health by Lowering Barriers to Electrophysiology in Genetic Model Organisms - Project Summary The nematode worm Caenorhabditis elegans has proven valuable as a model for many high-impact medical conditions. The strength of C. elegans derives from the extensive homologies between human and nematode genes (60-80%) and the many powerful tools available to manipulate genes in C. elegans, including expressing human genes. Researchers utilizing medical models based on C. elegans have converged on two main quantifiable measures of health and disease: locomotion and feeding; the latter is the focus of this proposal. C. elegans feeds on bacteria ingested through the pharynx, a rhythmic muscular pump in the worm’s throat. Alterations in pharyngeal activity are a sensitive indicator of dysfunction in muscles and neurons, as well as the animal’s overall health and metabolic state. C. elegans neurobiologists have long recognized the utility of the elec- tropharyngeogram (EPG), a non-invasive, whole-body electrical recording analogous to an electrocardiogram (ECG), which provides a quantitative readout of feeding. However, technical barriers associated with whole- animal electrophysiology have limited its adoption to fewer than fifteen laboratories world-wide. NemaMetrix Inc. surmounted these barriers by developing a turn-key, microfluidic system for EPG acquisition and analysis called the the ScreenChip platform. The proposed research and commercialization activities significantly expand the capabilities of the ScreenChip platform in two key respects. First, they enlarge the phenotyping capabilities of the platform by incorporating high-speed video of whole animal and pharyngeal movements. Second they develop a cloud database compatible with Gene Ontology, Open Biomedical Ontologies and Worm Ontology standards, allowing data-mining of combined electrophysiological, imaging and other data modalities. The machine-readable database will be compatible with artificial intelligence and machine learning algorithms. It will be accessible to all researchers to enable discovery of relationships between genotypes, phenotypes and treatments using large-scale analysis of multidimensional phenotypic profiles. The research and commercialization efforts culminate in an unprecedented integration of genetic, cellular, and organismal levels of analysis, with minimal training and effort required by users. Going forward, we envision the PheNom platform as a gold standard for medical research using C. elegans.
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