# Mechanistic Studies of Cytoplasmic            dsDNA-Sensing Pathways

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $5,619

## 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:** 10145282
- **Project number:** 3R01GM129342-02S2
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** JUNGSAN SOHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $5,619
- **Award type:** 3
- **Project period:** 2018-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145282

## Citation

> US National Institutes of Health, RePORTER application 10145282, Mechanistic Studies of Cytoplasmic            dsDNA-Sensing Pathways (3R01GM129342-02S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145282. Licensed CC0.

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