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 conditionsThe strength of Celegans derives from the extensive homologies between human and nematode genesand the many powerful tools available to manipulate genes in Celegansincluding expressing human genesResearchers utilizing medical models based on Celegans have converged on two main quantifiable measures of health and diseaselocomotion and feedingthe latter is the focus of this proposalCelegans feeds on bacteria ingested through the pharynxa rhythmic muscular pump in the worm s throatAlterations in pharyngeal activity are a sensitive indicator of dysfunction in muscles and neuronsas well as the animal s overall health and metabolic stateCelegans neurobiologists have long recognized the utility of the electropharyngeogramEPGa non invasivewhole body electrical recording analogous to an electrocardiogramECGwhich provides a quantitative readout of feedingHowevertechnical barriers associated with wholeanimal electrophysiology have limited its adoption to fewer than fifteen laboratories world wideNemaMetrix Incsurmounted these barriers by developing a turn keymicrofluidic system for EPG acquisition and analysis called the the ScreenChip platformThe proposed research and commercialization activities significantly expand the capabilities of the ScreenChip platform in two key respectsFirstthey enlarge the phenotyping capabilities of the platform by incorporating high speed video of whole animal and pharyngeal movementsSecond they develop a cloud database compatible with Gene OntologyOpen Biomedical Ontologies and Worm Ontology standardsallowing data mining of combined electrophysiologicalimaging and other data modalitiesThe machine readable database will be compatible with artificial intelligence and machine learning algorithmsIt will be accessible to all researchers to enable discovery of relationships between genotypesphenotypes and treatments using large scale analysis of multidimensional phenotypic profilesThe research and commercialization efforts culminate in an unprecedented integration of geneticcellularand organismal levels of analysiswith minimal training and effort required by usersGoing forwardwe envision the PheNom platform as a gold standard for medical research using Celegans