Investigating Conserved Host Pathways Linking Microbial Detection with Development

Living systems have evolved highly precise ways to sense and respond to microbial cues, yet the rules governing these interactions remain unclear. Understanding these mechanisms is essential not only for biology, but also for advancing biotechnology platforms that harness microbial products to control cell behavior. This project addresses a fundamental question in biology: how do animals interpret microbial cues to regulate development. By revealing how conserved biological pathways link bacterial sensing to developmental decisions, this work will advance understanding of host–microbe interactions. The results have the potential to inform strategies for marine ecosystem restoration, including enhancing larval recruitment in degraded habitats, while also establishing foundational principles for biotechnology applications that harness microbial cues to control biological processes. Discoveries from this research are thus expected to enable emerging biotechnology platforms, illustrating how fundamental insights can translate into new environmental and biomedical applications. The project will also support workforce development through hands-on research experiences for undergraduate and graduate students, including a course-based program that engages early-career students in discovery-driven science. In addition, this project advances NSF’s priorities in Biotechnology. This project uses the marine tubeworm Hydroides elegans as a model system to define how animals detect bacteria and initiate metamorphosis. The central hypothesis is that larvae use conserved pathways associated with the innate immune system, including components of the Toll-like receptor (TLR)/MyD88 signaling pathway, to distinguish between beneficial microbial cues that trigger development and pathogenic signals that activate defense, thereby directing distinct biological outcomes through NF-kB–dependent programs. To test this, the project will (1) identify and functionally characterize NF-kB homologs required for bacteria-induced metamorphosis, (2) determine whether beneficial and pathogenic bacteria activate overlapping or distinct host signaling pathways, and (3) identify the receptors responsible for detecting bacterial cues. The approach integrates RNA interference (RNAi), gene expression analysis, and bacterial genetic tools to causally link microbial signals to host developmental responses. By defining the molecular pathways that connect bacterial detection to developmental activation, this work will establish a mechanistic framework for how environmental microbes regulate animal life histories and reveal conserved principles of immune–developmental signaling. 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. NSF Award ID: 2539174 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Nicholas Shikuma | Institution: San Diego State University Foundation, SAN DIEGO, CA | Award Amount: $855,892 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2539174 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2539174.html