# Evolutionary dynamics of dense, spatially structured, and antagonistic microbial populations

> **NIH NIH R35** · CORNELL UNIVERSITY · 2024 · $54,724

## Abstract

Abstract
Microbes in host microbiomes, human infections and the natural environment often live in spatially structured
aggregates and interact antagonistically with each other. Toxin-mediated antagonistic interactions are
widespread in the gut, skin, and other human microbiomes, and protect these communities against external
invasion. Recent results suggest that spatial structure can strongly affect the evolutionary dynamics of
microbial populations, and, in turn, microbial interactions can feedback on the formation of spatial structure. For
example, we found that mechanical interactions among dividing cells in growing yeast colonies reduce the
power of natural selection by reducing the rates at which lower fitness strains go extinct and fitter ones expand
in these populations. Despite spatial structure and microbial interactions have a strong impact on the
evolutionary dynamics of microbes relevant for human health, most of what we know about microbial
evolutionary dynamics comes from experiments with well-mixed liquid cultures with limited interactions among
cells. To fill this gap, my group is interested in understanding quantitatively how spatial structure, mechanics
and biological interactions impact the adaptive evolutionary dynamics of microbial populations. We approach
this question via experimental evolution, synthetic biology, and mathematical modeling. In preliminary
experiments, we found that evolving yeast colonies selecting for faster expansion on agar surfaces results in
notable changes in cell shape: cells evolved from an ellipsoidally shaped ancestor to being elongated and
almost rod- like, changing the way cells interact mechanically when growing and dividing. We hypothesize that
an elongated cell shape is advantageous for faster expansion because it reduces cell packing, and that this
adaptive change is associated with changes in the way genotypes cluster in space leading to increased
genetic drift, the temporal change in allele frequencies due to chance events. Recently, we showed that a toxin-
producing microbe can only invade a landscape occupied by a weaker toxin-producer if its inoculum is larger
than a critical size, and that adaptive evolution can alter the dynamics of antagonism. We will experimentally
investigate the dependence of the critical inoculum size on the strength of the interaction, and we will study how
spatial structure controls the fate of mutations that confer resistance to the toxin produced by either the invader
or resident strain. Finally, we will investigate how antagonistic interactions among microbes affect the
dynamics of invasion in the gut of the nematode Caenorhabditis elegans: these experiments will help us
translate results obtained in simple laboratory settings to the more complicated but more realistic dynamics of
invasion of a host microbiome.

## Key facts

- **NIH application ID:** 11036611
- **Project number:** 3R35GM147493-02S1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Andrea Giometto
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $54,724
- **Award type:** 3
- **Project period:** 2024-02-16 → 2025-02-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11036611

## Citation

> US National Institutes of Health, RePORTER application 11036611, Evolutionary dynamics of dense, spatially structured, and antagonistic microbial populations (3R35GM147493-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11036611. Licensed CC0.

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