# Systems Approach to Immunity and Inflammation

> **NIH NIH U19** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $2,207,462

## Abstract

Summary
The innate immune response is a double-edged sword; it is absolutely required for host defense, but
unregulated, causes inflammatory disease. Diverse and potent mechanisms have evolved to recognize and
counter invading microorganisms. These include a variety of pattern recognition receptors, including Toll-like
receptors (TLRs), RIG-I-like receptors (RLRs), Nod-like receptors (NLRs) and C-type lectin like receptors
(CLRs) that recognize conserved molecular motifs on pathogens. While significant progress has been made in
identifying the ligands detected by these receptors and the signaling cascades that they activate, a number of
critical questions regarding the mechanisms that appropriately tailor the outputs of these pathways remain
unanswered.
Furthermore, the immune response to live pathogens is shaped by the interaction of multiple receptors and
their cognate signaling pathways. The aggregate response is complex and cannot be predicted from analysis
of each pathway in isolation; however, it is tractable using the tools of systems biology and forward genetics.
Over the past 15 years members of this U19 consortium have collaborated using cross-disciplinary approaches
to define the molecular mechanisms underlying the regulation of immune receptors and pathways. Their
genetic approaches have also linked the pathways to pathogenesis and to immunity in vivo. These studies
have also generated a significant body of work demonstrating cross-regulation between innate immune
receptors.
This U19 consists of two interrelated Projects that probe the innate immune response to infection. In Project 1,
the Beutler laboratory will work in close collaboration with the Aderem, Nolan, and Ulevitch laboratories, taking
a highly automated forward genetic approach to the analysis of innate immune signaling. In Project 2, the
Aderem laboratory will determine mechanisms by which the TLR and type I interferon pathways cross-regulate
each other. The Projects will be supported by three scientific Cores: The Signaling Core, will bring to bear
several novel technologies for highly multiplexed molecular phenotyping of immune cells. The Data
Management and Bioinformatics Core will support the individual Projects as well as the overall goals of the
program through integrated computational analysis of all large-scale datasets. The Human Correlation Core
will examine the relevance of mouse genes, demonstrated in Projects 1 and 2 to mediate innate immune
functions, in the analogous human pathways.

## Key facts

- **NIH application ID:** 9999444
- **Project number:** 5U19AI100627-09
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Richard J Ulevitch
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,207,462
- **Award type:** 5
- **Project period:** 2012-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999444

## Citation

> US National Institutes of Health, RePORTER application 9999444, Systems Approach to Immunity and Inflammation (5U19AI100627-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999444. Licensed CC0.

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