# Mechanisms of cell-size control in Gram-negative bacteria

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $308,800

## Abstract

Project Summary
To grow and survive, bacteria rely on a multitude of physiological processes occurring along and across the cell
envelope, including nutrient uptake, respiration, and the secretion of waste products. These processes are
sustained by a dense arrangement of proteins located within and along the cell envelope. To better predict
bacterial growth behavior in different environments it is thus essential to better understand how bacterial cells
control their envelope proteome depending on their cell-physiological state and the specific characteristics of the
environment they encounter. This research integrates experiments and mathematical modeling to promote such
a systems-level understanding of the cell envelope in rod-shaped Gram-negative bacteria.
Envelope proteins in Gram-negative bacteria are distributed across two membranes and the periplasmic space
enclosed by these membranes. As the dimensions of these envelope layers are inherently linked to the size of
the cell, this study tightly integrates cell-size control to investigate how envelope protein masses and envelope
size are regulated by the cell. Experimentally, microscopy, genetic engineering, and a novel biochemical assay
are combined to quantify changes in cell size and the envelope proteome across bacterial species and for a
broad range of physiologically distinct growth conditions. Mathematically, Bayesian inference and resource
allocation models are integrated to dismantle the interdependence of measured quantities and specifically probe
the role of two hypothesized constraints of envelope composition and cell size control: macromolecular density
and aspect-ratio maintenance. The three specific aims are: (i) Revealing the fundamental growth laws of
envelope composition and cell size in different Gram-negative species. (ii) Establishing a dynamical resource
allocation model to predict adjustment of cell size and envelope composition over the cell cycle. (iii) Probing the
molecular regulation of envelope-dependent aspect-ratio control.
Major pathogenic bacteria belong to the group of rod-shaped Gram-negatives considered in this study, including
five of the seven ESKAPEE pathogens known for their aggressive acquisition of multiple antibiotics resistance.
As such, this systematic study of envelope and size control builds an important physiological foundation for the
targeted development of novel prevention and treatment strategies against an increasing global health threat.

## Key facts

- **NIH application ID:** 10878258
- **Project number:** 1R01GM149611-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jonas B Cremer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $308,800
- **Award type:** 1
- **Project period:** 2024-06-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878258

## Citation

> US National Institutes of Health, RePORTER application 10878258, Mechanisms of cell-size control in Gram-negative bacteria (1R01GM149611-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10878258. Licensed CC0.

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