Defining the building blocks of multicellularity: adhesion, recognition, and immunity

The evolution of multicellularity was a pivotal transition that laid the foundation for cell biology, development, physiology, and immunity in animals. Building on our previous work in cell-cell adhesion and self/nonself recognition as unifying elements of multicellular development, in the next five years we will examine the evolutionary foundations of antibacterial immunity. Our work centers on sponges, invertebrate animals with unique relevance for identifying both anciently conserved and novel immune paradigms for regulating interactions with bacteria. Like all animals, sponges must defend against opportunistic pathogens, but like protists they feed by direct phagocytosis of bacteria. Also, living in aquatic habitats they are constantly bathed in environmental bacteria from which they cultivate complex communities of beneficial symbionts within their tissues. With genomic resources, a cell atlas, and transgenic tools in-hand, we are uniquely positioned to probe sponge immune pathways in unprecedented depth. Our preliminary findings have already revealed a novel family of glycan-binding pattern recognition receptors (PRRs) that have never before been studied. Characterizing their biochemical and functional properties will provide critical new insights into bacterial recognition and response. Furthermore, the glycan-binding region of these PRRs is composed of three-sided beta-helices that hold tremendous promise as novel diagnostic and therapeutic tools. We have also established that the versatile intracellular pathogen Legionella pneumophila can be used to infect sponges and thereby model an authentic immune response. As L. pneumophila infection has been extensively studied in human macrophages and amoebae, there exists a rich framework for comparing infection dynamics across nearly 1.8 billion years of evolutionary history, spanning the divide between unicellularity and multicellularity. Our research seeks to define foundational principles of immunity, bridging evolutionary biology and biomedical science to address critical challenges in health and disease. Project Number: 1R35GM161567-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: SCOTT NICHOLS | Institution: UNIVERSITY OF DENVER (COLORADO SEMINARY), DENVER, CO | Award Amount: $411,285 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 CDB-N (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11260481