Elucidating Chemical Signaling Mechanisms that Regulate Multicellularity and the Transmission of Infectious Disease

Trustees Of Indiana University, Bloomington IN

Investigators

Linked publications & trials

Abstract

Project Summary / Abstract Organisms rarely live in isolation. They live in complex multi-species communities where soluble chemical factors mediate cell-cell signaling, cooperation, and competition. Mutualist microbes exchange metabolites and signals to benefit their hosts in myriad ways, while parasites release virulence factors that harm their hosts. Microbes also exhibit similar chemically mediated benefits and challenges to one another in environmental and host- associated contexts. From a cellular perspective, even a multicellular organism can be considered a complex symbiosis of phenotypically distinct cells using chemicals to cooperate for the overall benefit of the ‘community’. My laboratory of chemists, biochemists, and biologists aims to discover the chemical languages that shape interactions within microbial communities and between microbes and their hosts. Our proposed work focuses on chemical signaling in three distinct areas. First, we aim to uncover chemical signaling processes that regulated key transitions in the origin of the first multicellular animals (e.g., formation of multicellular bodies and differentiation of cell types). We pursue this goal by identifying the chemical signals and mechanisms that regulate multicellular behaviors in some of the closest living relatives of animals—the unicellular holozoans Capsaspora owczarzaki, Ministeria vibrans, Salpingoeca rosetta, and Corallochytrium limacisporum. This work may reveal how the first animals evolved and may inform how the diverse cells within healthy animals develop and function. Second, we aim to uncover chemical signaling processes that enable the protozoan snail symbiont Capsaspora owczarzaki to colonize its snail host. This symbiont can kill the parasitic schistosomes that mature in snails before spreading to humans where they cause the neglected tropical disease schistosomiasis. Therefore, understanding Capsaspora’s ability to persist in snails and hunt schistosomes may improve its development as a biocontrol agent to curtail the spread of schistosomes through snails near human populations. Finally, we aim to uncover new chemical signals that regulate bacterial behaviors necessary for pathogenesis. By arresting these behaviors, we can disarm pathogens. Overall, our work will reveal previously unrecognized ways that symbionts and cells within animals communicate and compete on a chemical level. This work may be applied to reveal the most fundamental mechanisms of regulated multicellularity in animals, and it also may be applied to inform efforts to curtail the transmission and virulence of infectious diseases.