# Assembly and Maintenance of the Bacterial Cell Envelope

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2022 · $67,174

## Abstract

PROJECT SUMMARY
The cell envelope lies at the interface of bacterial pathogens and their host. It contains unique molecules that
are recognized by the innate immune system, and it is where key virulence factors are embedded. The cell
envelope and the biogenesis pathways that build it are also targets of many of our most effective antibiotic and
vaccine therapies. Because cell envelope biogenesis has been such a successful target, it has been an active
area of research for over half a century. Most of the genes responsible for the synthesis and remodeling of the
different surface polymers have been identified and their biochemical activities characterized. However, a
major gap in our knowledge is how these different pathways are coordinated with each other and how the cell
monitors the envelope for defects and directs their repair. This proposal focuses on investigating the
coordination between the synthesis of the distinct surface polymers and the repair of the envelope using the
model gram-positive bacterium Bacillus subtilis.
The gram-positive cell envelope is composed of distinct layers of surface polymers including lipid-linked
anionic polymers called lipoteichoic acids (LTAs), the multi-layered cell wall peptidoglycan (PG) and the distinct
anionic polymers called wall teichoic acids (WTAs) that are attached to it. Cell growth requires the coordinated
synthesis of these envelope layers, but the mechanisms underlying this coordination remain poorly
understood. A second outstanding question is how gram-positive bacteria monitor and repair defects in their
envelope layers. In preliminary work, I have discovered that conserved enzymes that synthesize PG and
transfer WTA onto it contain extracellular intrinsically disorder regions (IDRs). My data and previous studies in
my host lab suggest that these regions direct the synthases to gaps or defects in the cell wall meshwork to
fortify them. The goals of this proposal are (1) to establish how gram-positive bacteria monitor and repair their
cell envelope layers and (2) use directed and unbiased approaches to investigate the interplay between the
assembly of the PG and the teichoic acids.
This project will be carried out in the laboratory of Dr. David Rudner in the Department of Microbiology at
Harvard Medical School. I will be closely mentored by Dr. Rudner and will be embedded within a rich and
collegial scientific community committed to scientific exchange and discovery. The formative training and
connections that I make during my fellowship will be instrumental in launching my future career as an
independent research investigator.

## Key facts

- **NIH application ID:** 10463287
- **Project number:** 1F32GM146400-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Jennifer Dara Cohen
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463287

## Citation

> US National Institutes of Health, RePORTER application 10463287, Assembly and Maintenance of the Bacterial Cell Envelope (1F32GM146400-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10463287. Licensed CC0.

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