C.ELMi - A Smart Microscope for high-throughput behavior classification and supporting molecular analysis in C. elegans

Phenotypic behavior analysis in model organisms, such as the nematode Caenorhabditis elegans (C. elegans), is currently an obstacle in important research fields of aging or neurodegenerative disease. Existing tools for C. elegans behavior analysis are limited by manual, subjective evaluations, a lack of automation, scalability, and the ability to assess multiple behavioral traits simultaneously. There is a clear need for automated, objective, and cost-effective systems for high-throughput behavioral analysis and integration with molecular studies. This proposal aims to develop C.ELMi, a novel microscope designed to overcome these challenges. Combining hardware, software (microscopy and machine learning), and its applications, C.ELMi offers a user-friendly, scalable system for high-throughput studies and molecular analysis. C.ELMi enables 1) longitudinal tracking of survival, behavioral and morphological parameters (e.g., movement, social contacts, speed, and resting time), 2) automated long-term analysis of behavioral aberrations and individual identification, and 3) the selection of individuals for molecular analysis based on behavioral data. This will support transcriptomics, genome-wide RNAi screens,qPCR, metabolomics, or also proteomics. C.ELMi will support longitudinal studies on aging, neurodegenerative diseases, and the subsequent identification of transcriptomic alterations, offering a comprehensive and unbiased analysis of behavior alongside molecular mechanisms. The system's design is cost-effective, with a low manufacturing price, and it is intended to be open-source, making it accessible to both high-budget and low-budget laboratories. C.ELMi's proof of concept involves evaluating its accuracy in segmenting and tracking C. elegans and identifying those with abnormal behaviors, followed by RNA sequencing to validate molecular pathways. This approach will integrate behavioral and molecular data, providing unprecedented insights into the molecular basis of behavior in disease models. This system will revolutionize C. elegans research by enabling automated, high-throughput phenotypic analysis and molecular validation.