# Functional and Structural Dissection of Inflammasome Activation

> **NIH NIH R37** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $392,500

## Abstract

Project Summary/Abstract
Inflammasomes are multi-protein complexes that assemble in the cytosol in response to infection or other
noxious stimuli. Inflammasomes serve as platforms to activate inflammatory caspase proteases such as
Caspase-1. Active Caspase-1 initiates inflammation by cleaving pro-IL1B and pro-IL18 cytokines into their
active and secreted forms. Active Caspase-1 can also trigger a lytic form of cell death, called pyroptosis, by
cleaving and activating a pore-forming protein called Gasdermin D. Inflammasomes play critical roles in
initiating host defense against diverse viral, bacterial, fungal and protozoan pathogens. In addition, genetic
evidence from humans and mice has established that inappropriate inflammasome activation can cause
severe autoimmune and inflammation-driven diseases. However, the molecular mechanisms of how
inflammasomes detect pathogens and become activated remain poorly understood. This proposal focuses
on the NLRP1 inflammasome, which appears to have a novel but poorly understood mechanism of
activation. Prior studies have demonstrated that mouse NLRP1 is activated by a toxin produced by Bacillus
anthracis, but how this occurs and whether there are pathogen-encoded activators of human NLRP1
remains unclear. To address these gaps in our knowledge, this proposal has two aims: 1. Determine the
biochemical mechanism of NLRP1 activation; 2. Identify novel pathogen-associated enzymes that activate
NLRP1. Completion of these aims will increase our understanding of the mechanisms by which the innate
immune system detects and responds to pathogens.

## Key facts

- **NIH application ID:** 9942353
- **Project number:** 5R37AI075039-13
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** RUSSELL E VANCE
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2008-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942353

## Citation

> US National Institutes of Health, RePORTER application 9942353, Functional and Structural Dissection of Inflammasome Activation (5R37AI075039-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9942353. Licensed CC0.

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