# Regulation of pathogen sensing and inflammation by NLR proteins

> **NIH NIH R15** · FRANKLIN AND MARSHALL COLLEGE · 2024 · $384,940

## Abstract

Project Summary
The NLR (nucleotide-binding domain, leucine-rich repeat containing protein, also known as NOD-like receptor)
family is a diverse group of proteins that functions to regulate host immunity. Many of the NLRs have been shown
to regulate inflammasome formation and control caspase-1 activation, IL-1β/IL-18 secretion and inflammatory
cell death. In contrast a subset of NLR proteins negatively regulates different inflammatory pathways, typically
via inhibitory interactions with key signaling molecules. Nonetheless the molecular mechanisms that control the
negative regulation of inflammation are poorly understood. NLRC3 in particular has been shown to negatively
regulate several key inflammatory pathways. For example, NLRC3 has been shown to inhibit NF-κB and PI3K
pathways in response to TLR (or IGF-1R) signaling and proinflammatory cytokine secretion; alternatively, NLRC3
inhibits type I interferon production in response to cytosolic nucleic acid stimulation by regulating STING
trafficking. The molecular mechanisms to allow for NLRC3 to function in diverse pathways are poorly understood.
Understanding the molecular mechanisms of negative regulation of inflammation will be necessary for the
generation of new strategies to improve health. Aim 1 of my proposal uses classic biochemical and cell biological
techniques to examine the molecular determinants of novel protein-protein interactors with NLRC3. Our studies
suggest that one of these interactors negatively regulates type I interferon production. In aim 1 of our proposal
we will generate recombinant cell lines via CRISPR/Cas9, shRNA and overexpression to probe the specific role
of each PPI. In aim 2 we will investigate the molecular mechanism of innate immune signaling pathways that
are associated with NLRC3

## Key facts

- **NIH application ID:** 10974842
- **Project number:** 2R15GM134430-02
- **Recipient organization:** FRANKLIN AND MARSHALL COLLEGE
- **Principal Investigator:** Beckley K Davis
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $384,940
- **Award type:** 2
- **Project period:** 2019-08-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974842

## Citation

> US National Institutes of Health, RePORTER application 10974842, Regulation of pathogen sensing and inflammation by NLR proteins (2R15GM134430-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10974842. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*