SBIR Phase II: Development of a Novel Measurement Technology to Enable Longitudinal Multiomic Investigations of the Gut Microbiome

The broader impact of this Small Business Innovation Research (SBIR) Phase II project would be a significant increase the commercial, scientific, and human health potential of the microbiome field by enabling large-scale, dense longitudinal measurement and analysis of microbial RNA. This could enable: (1) a significant reduction in false discoveries caused by a lack of reproducible data; (2) a major cost reduction – ensuring these advancements are accessible to the entire industry; (3) high-frequency sampling, making time-series explorations routine; and (4) the creation of a large-scale database that contains both DNA and RNA data, which could lead to unprecedented discovery and validation of precision medicine biomarkers. Successful completion of this project could have a high likelihood of advancing the health and welfare of the American public, increasing the economic competitiveness of the United States healthcare and life sciences sector, and enhancing partnerships between academia and industry. The proposed project describes the development of an RNA feature to an existing microbiome measurement and analysis platform that consists of an automated sample collection system and an analytics engine for sequence data. Currently, the question of which genes are being expressed by gut microbes (which can be studied using RNA transcripts) is an extraordinarily promising research field for advancing the understanding of host-microbial interactions. This is because bacteria that make up a small amount of the gut microbiome can still influence the community dramatically through their gene expression. This can be overlooked by DNA sequence data, which only measures bacterial abundance. Despite this, RNA remains under-utilized, as RNA quickly degrades outside of the cell, and most laboratories lack the capability to measure RNA at any significant scale reliably. The main activities of this project will be (1) refining a process for RNA capture and storage, (2) integrating these into the automated hardware system, and (3) developing the methods and infrastructure for analysis of the resulting RNA datasets. This project will allow studies of gene expression in the gut microbiome to become commonplace, allowing researchers to discover more powerful clinically relevant biomarkers for precision medicine applications. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.