# Chemical Biology Approaches to Investigate Cell-Signaling and Competition in Complex Bacterial Communities

> **NIH NIH R35** · UNIVERSITY OF NEVADA RENO · 2020 · $357,540

## Abstract

The complex architectures of bacterial communities in their natural niches hinders our understanding of
the interspecies interactions that shape the overall population composition. The critical role bacteria play
in human health, either by carrying out essential processes such as food digestion or through invasive
infections that cause diverse chronic and acute diseases, highlight the need to develop new approaches
that will enable us to study complex bacterial populations, such as the human microbiome. Failing to do
so, will likely hinder further advancement in the field of sociomicrobiology and consequently prevent the
development of novel strategies to harness bacterial behaviors to improve the quality of life of millions of
people worldwide. The long-term goal of the research program is to utilize bacterial communication
pathways to study complex bacterial communities in their natural niches. To this end, in the past three
years, the quorum sensing (QS) circuits of a variety of bacterial species were studied and peptide-based
QS modulators with diverse activity profiles were developed. The goals for the next five years are to expand
the chemical toolbox available for QS modulation and utilize the developed QS modulators to probe the
effects QS has on the overall population composition of complex bacterial communities. The central
hypothesis is that QS, a cell-cell signaling mechanism that enables bacteria to assess their population
density through the production, secretion and detection of signal molecules, is involved in both intra-
species and inter-species bacterial communications, and has an important role in bacterial competition
and thus in shaping the overall population composition of complex communities. The rationale is that once
the role of QS in complex bacterial communities is determined and QS modulators capable of altering the
population composition are identified, an innovative approach to harness bacteria to improve human health
could be developed. Guided by strong scientific premise and preliminary results, this hypothesis will be
tested by combining traditional genetic microbiology along with chemical biology techniques,
computational modeling and structural biology analysis of peptide-based probes to uncover the role of QS
in complex bacterial communities. The approach is innovative, in the applicant’s opinion, because it
represents a substantial departure from the status quo by focusing on the effect QS has on inter-species
communication and competition, rather than on the role QS circuits play in intra-species communication.
The proposed research is significant because it is expected to both define the role bacterial communication
play in determining the overall population composition, and provide a novel strategy to harness bacterial
behavior to promote productive processes and attenuate harmful phenotypes to ultimately improve the
overall quality of life of millions of people worldwide.

## Key facts

- **NIH application ID:** 9980941
- **Project number:** 5R35GM128651-03
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Yiftah Talgan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,540
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980941

## Citation

> US National Institutes of Health, RePORTER application 9980941, Chemical Biology Approaches to Investigate Cell-Signaling and Competition in Complex Bacterial Communities (5R35GM128651-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980941. Licensed CC0.

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