# Equipment supplement - Unusual mechanisms of metal regulation in bacteria: from single molecules to single cells to cell communities

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $51,082

## Abstract

(Parent Award: R01 GM109993) Defining how cells regulate the uptake and efflux of transition metals
such as Zn is a key component in elucidating cellular mechanisms of metal homeostasis. Bacterial model
systems provide paradigms for understanding regulation mechanisms. In E. coli, the Zn2+-responsive
metalloregulator ZntR senses Zn excess and activates Zn efflux systems (e.g., ZntA), while Zur senses Zn
sufficiency and represses Zn uptake systems (e.g., ZnuABC), to keep this essential metal at appropriate
physiological levels in the cell. Past research has provided significant insights into the structure, function, and
mechanism of the protein players in regulating cellular metal concentrations, including metalloregulators, and
metal uptake/efflux transporters, etc. Yet, many mechanistic pathways are still poorly understood, especially
regarding spatially and temporally coordinated interactions among proteins and/or DNA that can reside at
different locations in the cell. The long-term goal here is to understand how metal regulation in the cell can be
manipulated for preventive and therapeutic purposes. Toward this goal, the PI has established an internationally
recognized and unique research program that applies and develops advanced single-molecule/single-cell
imaging approaches to interrogate and understand the mechanisms of bacterial metal regulation both in vitro
and in live cells, which are further enhanced by bulk biochemical/biophysical and protein/genetic engineering
approaches and by established collaborations with biologists and engineers. The research has led to the
discoveries of first-of-their-kind mechanisms of metal-responsive transcriptional regulation and metal efflux. The
objective of this renewal is to advance the study and understanding of bacterial metal regulation from single
molecules and single cells toward cell communities, comprising three aims that focus on Zn regulation in E.
coli: (1) define a “through-DNA” mechanism for Zn uptake-vs-efflux regulation; (2) define the mechanism of
ZnuABC for Zn uptake in the cell; and (3) dissect cell-cell interactions in Zn homeostasis within bacterial
communities. The research is significant because it will provide novel mechanistic insights into: how
metalloregulators can act on each other on DNA, beyond the present paradigm of “set-point” mechanism; the
spatiotemporal coordination of multicomponent Zn transporters for Zn uptake; and the cell-cell interactions in Zn
homeostasis within a bottom-up cell community; and because these insights will deepen our understanding of
cell biology of metals in general, including related processes in human cells, thus providing fundamental
knowledge for identifying causes or developing preventions of diseases that involve similar regulation processes
or for devising strategies to impair bacterial Zn homeostasis for antimicrobial treatments. The research is
innovative because it generates novel mechanistic concepts in metal regulation, uptake/efflu...

## Key facts

- **NIH application ID:** 11097401
- **Project number:** 3R01GM109993-10S1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Peng Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $51,082
- **Award type:** 3
- **Project period:** 2014-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11097401

## Citation

> US National Institutes of Health, RePORTER application 11097401, Equipment supplement - Unusual mechanisms of metal regulation in bacteria: from single molecules to single cells to cell communities (3R01GM109993-10S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11097401. Licensed CC0.

---

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