CAREER: Heterogeneity and alternate states in host-associated microbiomes

Emory University, Atlanta GA

Investigators

Abstract

Microbiomes are the communities of bacteria and other tiny microbes that live in and on other living things. These communities are part of the biology of normal, healthy organisms, yet certain changes in these communities can cause them to lose beneficial functions or even to become harmful to their hosts. This project will investigate how microbiome communities can resist change and what factors can lead to alternate states in the microbiomes of hosts. Microbiomes associated with humans and other large organisms can be difficult to study experimentally, but fortunately, simple hosts like the nematode worm Caenorhabditis elegans can be used to address these questions more easily. Although microbiomes in this small host consist of different bacterial taxa than are found in mammals, their microbiome communities have a similar ecology and can be used to learn general rules for how microbiomes respond to changing conditions. The project includes an educational component to help students build the quantitative skills necessary to succeed in modern science, using biologically motivated, math- and coding-focused course-based research experiences (CUREs). The educational activities developed as part of this project will be designed to build interdisciplinary skills, self-efficacy, and a strong understanding of research ethics among the next generation of working scientists. This study aims to better define stability and properties of alternate states of the microbiome, using wild-type C. elegans and mutants previously shown to have altered microbiome structure and/or stability. First, the range of "normal" and the properties of “stability” for a microbiome will be defined. Then, how disturbances such as antibiotic treatment interact with and alter community stability will be determined to better understand how perturbation-induced dysbiosis can be prevented or remediated. How host control contributes to microbiome stability and affects the landscape of available states will also be determined. Reaching this understanding will require identifying models that capture the salient features of stability in these noisy and dynamic systems. The use of a tractable model host will allow collection of high-quality data in large well-controlled experiments, suitable for testing alternate models of microbiome community ecology. 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.