# Project 4. Defining cell division pathways in Mtb.

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $704,587

## Abstract

Project 4, Abstract
Like all bacteria, Mycobacterium tuberculosis (Mtb) must coordinate major cellular processes, such as DNA
replication, with the synthesis and segregation of structural components in order to grow and divide. While the
processes governing cell division are reasonably well-described in model organisms, the mechanisms used by
mycobacteria are clearly different and less well understood. Defining the mechanisms governing the essential
process of cell division in Mtb will reveal new antimicrobial targets and provide the basis to understand how this
process is regulated during the slow-growing states that contribute to bacterial persistence during infection. This
project supports the program’s overall goal to understand pathways important to Mtb’s adaptation to
disease-relevant stress. It will synergize with other projects and leverage each of the cores.
Coordinating the cytokinesis with the cell cycle and the distribution of cellular material must be both temporally
and spatially regulated. Work in the project labs has shown that this coordination requires at least three distinct
regulatory paradigms. (1) The ordered assembly of the cell division complex, or “divisome” requires spatial and
temporal cues that may be provided by Ser/Thr protein kinases (STPK). (2) Extracytoplasmic enzymes
responsible for cell wall metabolism represent a distinct regulatory challenge, and are often controlled by protein-
protein interactions in the periplasmic space. (3) The coordination of processes necessary for cell division are
not restricted to the septum; fundamental metabolic changes are also likely necessary to provide the precursors
required for this major cellular event.
The goal of this project is to understand the regulatory paradigms that control mycobacterial cell division.
Specifically, the project will:
Aim 1. Characterize the role of protein phosphorylation in divisome dynamics. Synchronized Mtb cultures,
quantitative imaging, and biochemical approaches will be used to mechanistically characterize the role of
phosphorylation in the temporal and spatial regulation of divisome function.
Aim 2. Define and characterize extracytoplasmic complexes necessary for cell division. A combination of
genetic and physical approaches will be used to find interactions that are important for regulating enzymatic
activity and localization during cell division.
Aim 3. Characterize the links between cell division and metabolism. A combination of metabolomics and
genetics will be used to investigate the primary metabolic pathways necessary for cell division.

## Key facts

- **NIH application ID:** 10426182
- **Project number:** 5P01AI143575-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** SABINE EHRT
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $704,587
- **Award type:** 5
- **Project period:** 2020-06-12 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10426182

## Citation

> US National Institutes of Health, RePORTER application 10426182, Project 4. Defining cell division pathways in Mtb. (5P01AI143575-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10426182. Licensed CC0.

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