EleGantry: a software and hardware infrastructure to improve rigor and reproducibility within invertebrate research

PROJECT SUMMARY/ABSTRACT Caenorhabditis elegans is a mainstay of biomedical research and its growth as a model is likely to only increase in time. In particular, C. elegans is used with great effect to study neuronal circuitry, cell development and aging. However, as its use has increased, challenges with using C. elegans as a model have also made themselves more evident. One particularly noteworthy challenge is the variability between studies in reported wildtype animal lifespan, a common endpoint across disease models. Although it is conventionally known that C. elegans under normative growth conditions live an average of 3 weeks, a recent meta-analysis of C. elegans publications found that reported average ages ranged from 7 days to 35. The majority of C. elegans publications report only minimal methodological and environmental data and concluded that most variation could be ascribed to the accumulation of many small variables that often go unreported. As such, there is currently an unmet need in the C. elegans aging field for a system to better improve the methodology of how C. elegans experiments are conducted through removal of sources of variance and additional data recording and reporting. Ora Biomedical, Inc. is a longevity biotechnology company that identifies and develops small molecule healthy aging therapeutics using large-scale, unbiased, live animal phenotypic analysis with lifespan as a primary endpoint. We use custom built, fully scalable, automated state-of-the-art robotics and machine learning AI combined with health and survival analysis to perform high-throughput preclinical gerotherapeutics development that far surpasses the competition. With robust preclinical discovery at the heart of our approach, we identify novel aging targets and new interventions for known targets. Importantly, we leverage large-scale operations to perform drug-drug interaction studies to identify lifespan intervention combinations that produce breakthrough increases in healthy lifespan. The overarching goal of this SBIR proposal is to use massively high-throughput preclinical drug testing in a non-mammalian model system to identify compounds that extend organismal lifespan and/or effect the progression of age-associated diseases. The specific goal of this SBIR Phase I proposal is to develop EleGantry, a tool that will meet the need for improved rigor and reproducibility in C. elegans drug-discovery through increased depth of data collected and automation of several key steps of the standard C. elegans pipeline. These targeted steps that have a disproportionate large effect on the quality of C. elegans experimentation and subsequently are often key sources of variability between studies. Additionally, EleGantry will allow the reporting and publication of all of this valuable information so that replication of research and additional validation is made as effective and efficient as possible.