# Project 1: Transmission Biology of M. tuberculosis: Genes Required to Survive Stressful Transitions

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $756,424

## Abstract

Abstract
The goal of this project is to identify gene products whose inhibition could offer fresh approaches to reducing to
<1 the number of cases generated by the average infected person with tuberculosis (TB) in an uninfected
population: the R0. Specifically, using physiologically relevant fluids and environmental conditions, the goal is to
conduct a genome-wide survey for genes that Mycobacterium tuberculosis (Mtb) requires to survive the following
transitions it encounters in the course of transmission from one host to another: from a necrotic pulmonary lesion
to a cavity connected to an airway; from there to expelled micro-droplets that undergo dessication; and from
there to rehydration in the pulmonary alveoli of a new host. Inducible CRISPRi libraries of Mtb will be subjected
to each of these transitions to identify the genes on which Mtb depends to survive them. Collaboration with the
other Projects and Cores in this Program Project will allow us to prioritize individual mutant strains, subject them
to realistically-modeled mechanical aerosolization to test their ability to infect mice, and determine if guinea pigs
infected with them can transmit disease aerogenically. In parallel, TB drugs and tool compounds will be tested
for their impact on Mtb undergoing these transmission-related stresses.

## Key facts

- **NIH application ID:** 10404530
- **Project number:** 5P01AI159402-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** CARL Francis NATHAN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $756,424
- **Award type:** 5
- **Project period:** 2021-05-13 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404530

## Citation

> US National Institutes of Health, RePORTER application 10404530, Project 1: Transmission Biology of M. tuberculosis: Genes Required to Survive Stressful Transitions (5P01AI159402-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10404530. Licensed CC0.

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