GGrantIndex
← Search

The role of the epigenome-microbiome axis in phenotypic plasticity

$375,929R35FY2025GMNIH

Texas A&M University, College Station TX

Investigators

Abstract

Project Summary/Abstract: While it is well established that phenotypes can be influenced by epigenetics and the microbiome, emerging evidence shows that microbes can directly influence the host epigenome and vice versa, contributing an additional axis of variation affecting phenotypes. While the individual impacts of the microbiome on the host phenotypes are thoroughly studied, there remains a critical gap in knowledge as to how microbes and host epigenetics influence each other, and more broadly, how this additional axis of variation can influence larger scale processes of adaptation and phenotypic plasticity. The purple sea urchin, Strongylocentrotus purpuratus, has large range spanning Baja, Mexico to Alaska, with limited population structure due to the long dispersal distances of their planktonic larvae, but evidence of local adaptation to pH. Further, they exhibit one of the best studied examples of adaptive phenotypic plasticity, morphological extension of the arms in response to low food availability. In addition to being a well poised model to study adaptive processes in the face of high gene flow and phenotypic plasticity, S. purpuratus has been used for decades as a model organism due to its unique evolutionary position as a deuterostome invertebrate, a highly characterized immune response that is homologous to vertebrates, well described genomic resources, and a transparent larval stage that enables easily trackable cell biology. Our goal for this five-year project is to use S. purpuratus to study the relative roles of microbes and the epigenome on molecular and morphological phenotypes and how they contribute to adaptive processes and phenotypic plasticity. In this project, we will profile natural microbial communities in the seawater across a latitudinal range and run controlled experiments on early embryos to reveal how natural microbial communities in the water, external to larvae, influence the development of the larval immune system and epigenome. Embryos collected from sites spanning >1000 miles will be reared in the presence or absence of natural microbial communities, and we will quantify the development of key immune cells and responses to known pathogens. In concert, we will profile genome-wide changes in gene expression, DNA methylation, and chromatin accessibility. We will integrate this dataset through novel analytical approaches to reveal core mechanisms underlying immune development in wild populations and the role of adaptive processes and genetic background in shaping these patterns. Additionally, we will test the role of internal gut microbes on adaptive phenotypic plasticity through modulation of the host epigenome using targeted pharmacological agents. The proposed work will encompass the core research in my lab and connect to our other investigations of mechanisms underlying phenotypic plasticity in other marine invertebrate models. Our innovative approach to connect interactions between the microbiome and the host epigenome to larger scale processes of adaptation and plasticity will lay the foundation for my highly integrative research program.

View original record on NIH RePORTER →