# Chemical Strategies to Modulate Intercellular Bacterial Communication

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $368,592

## Abstract

PROJECT SUMMARY/ABSTRACT
This MIRA proposal outlines an integrated research program at the interface of chemistry and biology focused
on cell-cell communication in bacteria, or “quorum sensing” (QS). QS has a major impact on human health,
with some of the most common pathogens utilizing this sensing mechanism to regulate virulence—i.e., the
ability to initiate infection—once sufficient cells have amassed to overwhelm a host. Understanding the
molecular mechanisms of QS, its role in mixed microbial communities, and its impact on both acute and
chronic disease remain pressing and unaddressed challenges in the field. For example, our understanding of
how QS signaling molecules interact with their target protein receptors to activate or inhibit QS pathways is
limited to four species in Gram-negative bacteria. Further, with an increasing awareness of the importance of
microbial communities (i.e., our “microbiomes”) to human health, it is astonishing how little we know about
the role of chemical signaling between these organisms in the maintenance (or disruption) of healthy microbial
consortia. As bacteria use simple chemical signals to regulate QS, synthetic chemists and chemical biologists
are well positioned to address these problems and other related challenges at the molecular level. With support
from the NIH over the past decade, the PI has advanced the development of synthetic ligands that modulate QS
signaling systems in Gram-negative bacteria and has shown that these ligands can strongly attenuate QS-
controlled behaviors in many pathogens. This past work situates her ideally to lead this research project.
 The overall vision for this MIRA project is to build on the PI's 12-year foundation of results and leadership
in this area and apply a chemical approach to expand the understanding of QS across multiple scales—from
individual QS signal:receptor interactions to signaling in a single species to signaling within mixed bacterial
populations to interactions of the community with a host. We will achieve this vision through the pursuit of
three broad Goals: (1) the development of new small molecules capable of strongly modulating QS in Gram-
negative bacteria with high potencies, stabilities, and defined modes of action; (2) the application of these
molecules and new chemical strategies to delineate the biochemical mechanisms of QS; and (3)
characterization of the roles of QS in mixed microbial environments relevant to human health. These three
Goals will be pursued through an integration of chemical synthesis, chemical biology, bacteriology,
biochemistry, structural biology, and genomics. Studies will be performed in the PI's laboratory at the UW–
Madison and with a team of committed collaborators with expertise in QS and methods critical to this project.
The overall outcome of this project will be a drastically increased and rigorously tested understanding of QS in
bacteria and its role in biologically significant environments, and a suite of ne...

## Key facts

- **NIH application ID:** 10145034
- **Project number:** 5R35GM131817-03
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Helen E. Blackwell
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $368,592
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145034

## Citation

> US National Institutes of Health, RePORTER application 10145034, Chemical Strategies to Modulate Intercellular Bacterial Communication (5R35GM131817-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145034. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*