# Charge matters: Pursuing the most common, and least understood molecular interactions in cells

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $553,000

## Abstract

Charge matters: Pursuing the most common, and least understood
molecular interactions in cells
PROJECT SUMMARY / ABSTRACT
The long-term objective of the Süel lab is to determine and understand how ion fluxes and electrostatic
interactions regulate fundamental biological processes that promote stress tolerance in bacteria.
The central problem to be addressed: The vast majority of molecular interactions that occur within any living
cell have remained obscure. How can this be? Nearly all molecular interactions that have been studied to date,
and on which our current understanding of biology is based on, are covalent interactions. These interactions are
strong, making them suitable for experimental measurements. However, the vast majority of interactions among
molecules within the cell are non-covalent interactions that are based on electrostatics. Electrostatic interactions
can be weak and short-lived, and thus their measurements pose a great technical challenge. Consequently, how
such interactions are regulated and what functions they play in cells remains largely unknown. To bridge this
gap, we propose a research program to develop new devices, techniques, and a theoretical framework to
investigate the functional roles of electrostatic interactions, specifically in bacterial cells and biofilm communities.
Impact: The proposed work aims to investigate the regulation of ionic interactions and their functional roles in
bacteria, to better understand and control their tolerance to antibiotics. The resulting findings will determine how
changes in ionic strength and composition affect cell physiology. We will thus begin to characterize the dynamics
of the prokaryotic “metallome”. We will also integrate quantitative experiments with physics-based theoretical
approaches to identify general principles governing electrostatic interactions that can be applied beyond our
bacterial model systems. Given the tremendous number of ionic interactions within any given cell, it is very likely
that our work will uncover a new layer of molecular regulation of fundamental biological processes. Specifically,
we postulate the hypothesis of “ionic allostery”, where we propose that cells regulate their cytoplasmic ion
composition to modulate electrostatic interactions, and thereby globally regulate transcription and translation. In
particular, ionic interactions may play a crucial role in bacterial cell fate decisions, such as entry into, and exit
from dormancy, which is the major cause of antibiotic resistance. Our work will thus reveal whether “the central
dogma of biology” is modulated by changes in the ionic composition and strength of the cytoplasm and provide
a new paradigm for understanding and controlling the regulation of fundamental stress responses in bacteria.

## Key facts

- **NIH application ID:** 10529306
- **Project number:** 5R35GM139645-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Gurol Mehmet Suel
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $553,000
- **Award type:** 5
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10529306

## Citation

> US National Institutes of Health, RePORTER application 10529306, Charge matters: Pursuing the most common, and least understood molecular interactions in cells (5R35GM139645-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10529306. Licensed CC0.

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