# Signal Integration during Phagocytosis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2024 · $372,885

## Abstract

Morrissey
Project Summary: (30 lines)
The long-term goal of this project is to understand how cells control their sensitivity to external stimuli.
Macrophages are a particularly interesting example of this because they constantly encounter background
stimuli, like IgG, in their surrounding environment. Macrophage signaling pathways are carefully tuned to
rapidly detect IgG-bound pathogens without reacting to healthy cells. Macrophages respond to IgG by
activating phagocytosis and/or inflammation. The short-term goal of this project is to define how macrophages
set a response threshold for these outputs. We are approaching this problem from two directions. The first
direction is examining how receptor clustering or co-clustering affects macrophage sensitivity. Our previous
data shows that clustering of activating ligands enhances activation of the Fc Receptor, and increases
phagocytosis. Phagocytosis is also controlled by inhibitory ‘Don’t eat me’ signals on viable cells. We are now
expanding our studies to examine how clustering of inhibitory ligands, and co-clustering of inhibitory and
activating ligands affects phagocytosis. This will suggest how ligand or receptor pattern can tune macrophage
sensitivity. Our second direction is examining the intracellular signaling that filters out sub-threshold stimuli.
Our preliminary data suggests that a higher IgG signal is required for inflammation than phagocytosis. We will
address the following questions: What parameter do macrophages measure to determine IgG signal intensity –
signal duration, IgG density, or total number of IgG molecules? What is the molecular breakpoint in the IgG
signaling pathway that is only activated by high IgG? How does IgG stimulus intensity affect signaling
dynamics in the NFkB and MAPK signaling pathways? Overall, this will suggest how macrophages are able
generate two separate responses from a single input based on dose.

## Key facts

- **NIH application ID:** 10828397
- **Project number:** 5R35GM146935-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Meghan A Morrissey
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $372,885
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828397

## Citation

> US National Institutes of Health, RePORTER application 10828397, Signal Integration during Phagocytosis (5R35GM146935-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10828397. Licensed CC0.

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