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

> **NIH NIH R35** · CORNELL UNIVERSITY · 2024 · $382,748

## 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:** 10870149
- **Project number:** 5R35GM147493-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Andrea Giometto
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $382,748
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870149

## Citation

> US National Institutes of Health, RePORTER application 10870149, Evolutionary dynamics of dense, spatially structured, and antagonistic microbial populations (5R35GM147493-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10870149. Licensed CC0.

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