# Local and global regulation of bacterial growth

> **NIH NIH R35** · JOHNS HOPKINS UNIVERSITY · 2020 · $52,866

## Abstract

To impact human health, bacteria must reproduce through successive rounds of growth and division.
Moreover, bacterial cells must adapt their growth to changing environmental conditions, including changes in
nutrient availability or the presence of antibiotics, to ensure survival. In our proposed work, we focus on two
questions relevant to bacterial growth and adaptation. In the first, we ask how do bacterial cells locally regulate
growth during cell division (cytokinesis)? To address this question, we will build on our recent work
demonstrating that the conserved polymerizing GTPase FtsZ is a dynamic regulator of cell wall synthesis and
remodeling during cell division. This idea represents a paradigm shift in defining FtsZ as an active regulator,
rather than passive scaffold, for cell wall metabolism. We will leverage our expertise in bacterial genetics,
imaging, biochemistry, and in vitro reconstitution to map the players and mechanisms in two signaling
pathways from FtsZ to cell wall metabolism we identified in our model organism, Caulobacter crescentus.
Given the urgent need for new antibiotics and proven efficacy of the cell wall as an antibacterial target, a
complete understanding of the mechanisms and regulation of cell wall metabolism is a critical goal. In our
second question, we ask how do bacteria adapt to changing nutrient availability and other stresses? We
recently described the role of a conserved transcriptional regulator called CdnL in regulating metabolism,
specifically in upregulating biosynthetic pathways, in Caulobacter. In addition, we have observed that CdnL is
cleared from the cell during nutrient limitation in a manner dependent on the signaling alarmone ppGpp,
suggesting a mechanism by which cells may downregulate proliferative processes when nutrients are scarce.
We will use a combination of genetic, genomic, and biochemical approaches to determine the contributions of
CdnL inactivation and ppGpp to reprogramming transcription to ensure bacterial survival during nutrient
limitation and other stresses. As both CdnL and ppGpp are implicated in adaptation to a variety of stresses in
diverse bacteria, this work will inform our understanding stress and antibiotic resistance mechanisms in
important bacterial pathogens.

## Key facts

- **NIH application ID:** 10205225
- **Project number:** 3R35GM136221-01S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Erin D Goley
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $52,866
- **Award type:** 3
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205225

## Citation

> US National Institutes of Health, RePORTER application 10205225, Local and global regulation of bacterial growth (3R35GM136221-01S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10205225. Licensed CC0.

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