# RESEARCH PROJECT 2

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $95,687

## Abstract

PROJECT 2: GENETIC IDENTIFICATION OF HOST INNATE PATHWAYS THAT 
CONTROL BACTERIAL PATHOGENESIS 
SUMMARY 
Phagocytes of the mammalian innate immune system, in particular macrophages and neutrophils, form the first 
line of defense upon bacterial infection and are armed with powerful mechanisms to limit bacterial growth and 
eradicate invaders. Bacterial pathogens, however, have evolved mechanisms to thwart these killing 
mechanisms of phagocytes, and to persist in human tissues. In addition to having direct antimicrobial activity, 
macrophages and neutrophils also initiate and shape powerful inflammatory responses that dramatically 
influence disease. Indeed, the inflammatory pathways elicited by each of the pathogens involved in this study - 
Mycobacterium tuberculosis (Mtb), Staphylococcus aureus (SA), and Chlamydia trachomatis (CT) - play major 
roles in bacterial persistence in tissues and in promoting disease. Pathogens must subvert these cells in order 
to grow and persist, but the host genes and cellular pathways that dictate the outcome of infection are not 
entirely clear. The broad idea of this proposal is to use unbiased, systematic approaches to probe the intimate 
interactions between pathogen and innate immune cells, and to use this information to make predictions about 
bacterial infectivity that will be tested in human samples in an iterative fashion to model host response during 
infection. We propose to systematically identify innate immune gene networks that underlie pathogenesis in 
clinically relevant model systems of infections with these three important bacterial pathogens. Using powerful 
CRISPR-based knockout strategies in both ex vivo infections and in mouse models, coupled with innovative 
approaches to identify functionally relevant polymorphisms in clinical samples, we seek to dramatically 
increase our understanding of infection biology of humans. We anticipate that these insights, coupled with the 
other elements of the HPMI Center, will point to novel vulnerabilities with therapeutic relevance.

## Key facts

- **NIH application ID:** 10224018
- **Project number:** 5U19AI135990-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JEFFERY S COX
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $95,687
- **Award type:** 5
- **Project period:** 2018-08-17 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224018

## Citation

> US National Institutes of Health, RePORTER application 10224018, RESEARCH PROJECT 2 (5U19AI135990-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10224018. Licensed CC0.

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