# Phospholipase C Isozymes

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $427,684

## Abstract

ABSTRACT
Biological membranes create compartments within cells and demarcate the outsides of cells from their insides.
Beyond their role as physical barriers, lipid membranes also are used as platforms to organize biological
processes essential for life: Membrane surfaces are unique for the exceptional ability to coalesce, organize, and
regulate biological complexes necessary to transmit information between cells and among cellular
compartments. Certain of these biological complexes are core nodes that coordinate diverse inputs into
conserved outputs. One such core node is organized and orchestrated by the phospholipase C gamma (PLC-)
isozymes in response to diverse transmembrane receptors including a host of receptor tyrosine kinases and
immune receptors. We will study this core node as a “Rosetta Stone” to learn the inherent and emergent
properties of signaling at biological membranes. By systematically and quantitatively comparing how properties
of this core node and associated cellular responses are altered for different classes of input receptors and in
different cell types, we will derive fundamental and guiding principles about how cells and tissues execute precise
signaling within the physical-chemical constraints of their biological membranes. This goal will be accomplished
using a highly collaborative and interdisciplinary approach: Detailed structural, biophysical, and biochemical
studies of purified proteins and complexes will guide complementary studies of reconstituted nodes on self-
assembled lipid bilayers or re-engineered in cells to be controlled and imaged with light. Data from these studies
will inform computational models based on a newly-developed frameworks describing core nodes operating at
membranes that will be used to predict signaling kinetics, efficiency, and dynamics in response to changes in
core components, inputs, and feedback regulation. Together, these studies will reveal critical insights into the
function and regulation of the PLC- isozymes downstream of multiple receptor types. These studies will also
advance our overall goal of a deeper, yet more parsimonious, understanding of signaling at biological
membranes.

## Key facts

- **NIH application ID:** 10829416
- **Project number:** 5R35GM149299-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** JOHN E SONDEK
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,684
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829416

## Citation

> US National Institutes of Health, RePORTER application 10829416, Phospholipase C Isozymes (5R35GM149299-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10829416. Licensed CC0.

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