# Mechanistic Studies of Cytoplasmic dsDNA-Sensing Pathways

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $58,212

## Abstract

Project summary
The presence of dsDNA in the cytoplasm signals serious problems in eukaryotic cells, ranging
from dysfunctional mitochondria to pathogen invasion. In mammals, the innate immune system
detects these rogue dsDNA and initiate inflammatory responses. Cytoplasmic dsDNA sensing
pathways are integral to host defense against numerous pathogens, and their malfunctions are
also implicated in various human maladies.
Here, we will define the molecular mechanisms by which cytoplasmic dsDNA sensors initiate
host innate immune responses in a coordinated fashion. In Aim 1, we will resolve several
controversies regarding the activation mechanism of cGAS such as why dsDNA length matters
(or not), what the role of N-domain is, and how cGAS dimerizes on dsDNA. In Aim 2, we will
resolve a fundamental mechanistic question in innate immunology as to what defines the
dsDNA specificity of cGAS, AIM2, and IFI16. We will then test whether cellular RNA can act as
a buffer to minimize the spurious activation of these sensors. In Aim 3, we will determine
whether differential kinetics of cGAS, AIM2, IFI16, and the TREX1 nuclease can shape the
overall host response against cytoplasmic dsDNA. We will then investigate agonism and
antagonism among these sensors in generating well-balanced host responses against
cytoplasmic dsDNA.

## Key facts

- **NIH application ID:** 10414309
- **Project number:** 3R01GM129342-03S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** JUNGSAN SOHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $58,212
- **Award type:** 3
- **Project period:** 2018-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414309

## Citation

> US National Institutes of Health, RePORTER application 10414309, Mechanistic Studies of Cytoplasmic dsDNA-Sensing Pathways (3R01GM129342-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10414309. Licensed CC0.

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