# Identifying the Rules Governing Host-Microbiome Composition and Function

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $395,000

## Abstract

Project Summary/Abstract
All eukaryotes harbor host-associated microbiomes. Determining what regulates host-microbiome function has
the potential to revolutionize our approaches towards maintenance of host health. Host genetics and the
environment are two key factors that contribute towards host-microbiome composition and function. We aim to
advance our understanding of the relative roles of these two factors in regulating assembly of microbial
communities, short-term changes in these communities through ecological succession, and long-term changes
through evolutionary processes. Further, microbiomes are complex biological networks. Understanding the
underlying structure of ecological interactions within these networks can improve predictions for when and how
microbiomes might confer beneficial versus deleterious functions associated with disease. Our lab aims to
advance fundamental understanding of host-microbiomes by leveraging the microbiomes of microbes.
Specifically we employ single-celled eukaryotic phytoplankton as a highly-tractable experimental system. To
further these goals we will focus on the following three themes over the next five years. (1) We will couple the
unparalleled diversity of phytoplankton with bacterial –omics approaches to test how microbiomes assemble in
response to host genetics. By assessing bacterial gene expression responses to host genetics, in tandem with
fluctuating environmental conditions, this work will lend insights in to the host genetic x environmental forces
that drive microbiome assembly of eukaryotic microbiomes. (2) We will evaluate mechanisms of microbiome
change for maintenance of host homeostasis in fluctuating environments, including ecological shifts in bacterial
taxonomic composition, shifts in bacterial gene expression, and bacterial strain evolution. It is important to
understand the relative roles of these mechanisms because each occurs over different timescales and their
effects can have varying degrees of permanence on their host. (3) We will leverage classical community
ecology theory in biological networks with recent advances in flow cytometry bacterial fingerprinting to
characterize traits of transient versus stable microbiome networks. We will quantify bacteria-bacteria
interaction strengths within naturally assembled and engineered microbiomes to understand how network
structure contributes to transitions between host health and disease states. Additionally, our research program
will elucidate the implications of declining microbial diversity on eukaryotic host health. We will study host-
microbiome co-evolutionary mismatches, such as those caused by humans consuming processed diets and
living in human-built environments that differ from those of our evolutionary history. Ultimately, our work will
leverage a highly tractable experimental system to advance our understanding of the microbiomes that
modulate human health.

## Key facts

- **NIH application ID:** 10458046
- **Project number:** 5R35GM142938-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Sara Lindsay Jackrel
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458046

## Citation

> US National Institutes of Health, RePORTER application 10458046, Identifying the Rules Governing Host-Microbiome Composition and Function (5R35GM142938-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10458046. Licensed CC0.

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