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

Award Number: R35GM161567
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $411,285 )
2026	2026	UNIVERSITY OF DENVER	2199 S UNIVERSITY BLVD RM 222	DENVER	CO	80210	DENVER	USA	Biomedical Research and Research Training	000	1	3/3/2026	NEW	$411,285
														Subtotal = $411,285

Grand Total All Awards = $411,285

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

Award Number: R35GM161567

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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