# Mechanistic Elucidation of Inflammasome Assembly and Regulation

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $442,500

## Abstract

Abstract
Inflammasomes are supramolecular signaling complexes that activate a subset of caspases
known as inflammatory caspases such as caspase-1. Upon stimulation by microbial and
damage-associated signals, inflammasomes assemble to elicit the first line of host defense by
proteolytic maturation of cytokines IL-1β and IL-18, and by induction of pyroptotic cell death.
Assembly of an inflammasome requires activation of an upstream sensor, a downstream
effector, and in most cases an adaptor molecule such as apoptosis-associate speck-like protein
containing a caspase recruitment domain (ASC). Depending on whether ASC is required,
inflammasomes can be categorized into ASC-dependent and ASC-independent
inflammasomes. Despite the biological importance of inflammasomes in innate immunity, no
structural and mechanistic information is available. In this application, we propose structural,
biochemical, biophysical and cell biological studies on AIM2, NLRP3 and NAIP inflammasomes,
which are representative members of ASC-dependent and ASC-independent inflammasomes.
The key structural scaffolds for the assembly of these inflammasomes are composed of
filaments of Pyrin domains (PYD) and caspase recruitment domains (CARD), and polymerized
disk-like structures by nucleotide-binding domains (NBD).
 Inflammasomes have been implicated in many human diseases. Most notably, failure to
curb the activity of inflammasomes is linked to autoinflammatory conditions such as familial
Mediterranean fever and NLRP3-associated periodic syndromes including familial cold
autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological
cutaneous and articular syndrome–neonatal onset multisystem inflammatory disease. As
predisposing factors, inflammasome component proteins have been associated with many
inflammatory diseases such as psoriasis, lupus, and inflammatory bowel diseases such as
ulcerative colitis and Crohn's diseases.

## Key facts

- **NIH application ID:** 9979736
- **Project number:** 5R01AI124491-05
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Hao Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,500
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979736

## Citation

> US National Institutes of Health, RePORTER application 9979736, Mechanistic Elucidation of Inflammasome Assembly and Regulation (5R01AI124491-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979736. Licensed CC0.

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