# Community-derived zinc metal regulation from monolayer to biofilm.

> **NIH NIH F32** · CORNELL UNIVERSITY · 2022 · $67,582

## Abstract

Project Summary and Abstract
 In humans, the gut is home to the most extensive set of diverse bacteria actively working together to break
down nutrients for consumption, defend against pathogens, and train the immune system, as well as actively
communicating with the host cells to optimize their survival. The gut microbiome formed shortly after birth
changes over time in response to the diet and overall health of the host. When a pathogen invades the gut and
adversely affects the host’s health, it is treated with antibiotics. However, the treatment has the side effect of
indiscriminately altering the gut microbiome, leaving the host even more vulnerable to a future infection.
Communities of bacterial cells maintain a state of homeostasis by actively communicating with each other and
the host. This signaling system has the potential to serve as an innovative approach to treat virulent pathogens
by recruiting the microbiome’s own defense system. However, it is unclear what metabolites serve as a
signaling molecule to coordinate behavior. Transition metals play significant roles as micronutrients necessary
to carry out complex chemical reactions required to sustain life. Consequently, their concentrations inside the
cells are tightly regulated. This study focuses on zinc metal homeostasis due to its vital role in catalytic,
structural, and regulatory functions in Escherichia coli, a model Gram-negative bacterium and a common
bacterium in the environment, foods, and intestines. The overall objective of the proposed work is to determine
whether zinc can act as a chemical cue to coordinate behavior in a community of cells in the context of metal
homeostasis. My central hypothesis is that zinc acting as a signaling molecule can influence the cell’s
neighborhood gene expression state to account for a changing environment in which the micronutrient is in low
supply, excess, or used as a form of attack by a pathogen or the immune system. The hypothesis will be tested
using combined approaches of microfluidics devices, chemical/genetic manipulations, optogenetics,
single-molecule spectroscopy, and bulk biophysical/biomolecular/cellular assays. The proposed research has
two specific aims: 1) Define the coordination of uptake and efflux capabilities among individual cells in a
community as a function of zinc exposure. 2) Define the relation of periplasmic zinc concentration changes
among individual cells in a community upon perturbation of their metal homeostasis. The applicant will be
advised by a mentoring team that includes a chemist with expertise in single-molecule spectroscopy of
bacterial metal uptake/efflux pumps, a biomedical engineer with expertise in microfluidic systems, and a
microbiologist with expertise in bacterial metal homeostasis. The broader impact of this research is the creation
of a quantitative model to describe how zinc metal homeostasis is achieved at the community level and
delineate the role of the individual cells in a colony in f...

## Key facts

- **NIH application ID:** 10462373
- **Project number:** 1F32GM146364-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Felix Steven Alfonso
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462373

## Citation

> US National Institutes of Health, RePORTER application 10462373, Community-derived zinc metal regulation from monolayer to biofilm. (1F32GM146364-01). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10462373. Licensed CC0.

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