# Investigating the molecules and mechanisms of bacterial cell-cell interactions

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $418,750

## Abstract

PROJECT SUMMARY
In nature, bacteria typically exist within multispecies communities. Bacterial communities play vital roles in
shaping the environment and their plant and animals. In spite of the prevalence and importance of microbial
communities, important gaps still remain in our understanding of how bacteria interact within these microbiomes.
Our lab’s NIGMS-relevant research is focused on investigating the chemical, molecular, and genetic
mechanisms bacteria use to chemically and physically interact within multispecies communities. We focus on
the soil microbiome as our model system: the soil is not one of the most phylogenetically diverse microbial
environments on the planet, but soil microbes are also the source of the majority of our antibiotics and many
other therapeutics. Therefore, understanding the mechanisms bacteria use to interact within this natural
environment will not only provide a systems-level understanding of complex natural microbiome interactions but
also provide us with potential chemical tools and therapeutic leads to manipulate bacterial behavior. These
bacterially generated compounds are celled specialized or secondary metabolites. These secreted chemical
cues can act as cell-cell communication signals that influence the physiology and metabolism of neighboring
bacteria. They play key roles in bacterial differentiation, or the development of transcriptionally distinct,
heterogeneously expressed subpopulations of cells. We focus on the soil and probiotic bacterium Bacillus
subtilis, which can differentiate into cells that are making biofilm matrix, swimming, or sporulating, among others.
We are interested in understanding the transcriptional specificity, ancestral lineages, and spatial distributions of
this cellular heterogeneity as well as what roles specialized metabolites play in its development. We also aim to
discover specialized metabolites involved in interspecies cell-cell communication to expand our understanding
of chemical interactions in native microbiomes and obtain chemical tools to modulate bacterial physiology.
Finally, we seek to identify the genetic and molecular mechanisms these extracellular signals use to impact
bacterial transcription, heterogeneity, and metabolic activity. This research is significant because it will reveal
fundamental information about the chemical and genetic mechanisms bacteria use to interact with one another.
Our results will deepen our molecular understanding of cell-cell interactions within microbial communities as well
as enable the development of targeted interventions to manipulate microbial behavior in environmentally and
therapeutically important bacteria.

## Key facts

- **NIH application ID:** 10406576
- **Project number:** 1R35GM145261-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Elizabeth Anne Shank
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $418,750
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406576

## Citation

> US National Institutes of Health, RePORTER application 10406576, Investigating the molecules and mechanisms of bacterial cell-cell interactions (1R35GM145261-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10406576. Licensed CC0.

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