# Sensing and modulating the chemokine environment with synthetic cells

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $234,000

## Abstract

Project Summary
Gradients of chemokines control physiologic trafficking of multiple cell types, and many of these same
chemokines drive multiple diseases, including cancer, atherosclerosis, and neurodegeneration. Controlling
chemokine gradients also offers novel opportunities to improve recruitment of therapeutic cells to target
sites for regenerative medicine. Critical functions of chemokines and chemokine receptors in biomedicine
has motivated ongoing development of new pharmaceutical agents regulating these pathways. However,
clinical translation of compounds targeting chemokine signaling remains slow, due in part to unresolved
basic questions about how local gradients of chemokines control cell migration, particularly in diseased
tissues with loss of normal tissue architecture. While local gradients of chemokines are recognized as key
determinants of cell movement, methods to measure or manipulate the chemokine environment
immediately adjacent to cells remain limited. The objective of this proposal is to develop and utilize synthetic
cells as a synthetic biology tool to manipulate the chemokine environment that will help address how local,
cell-adjacent chemokine gradients steer chemotaxis of cells. Specifically, we will focus on two chemokine
receptor pathways, CXCL12-CXCR4 and CCL21-CCR7, strongly associated with progression of several
common diseases and promising targets for cell-based regenerative therapies. Synthetic cells can be
engineered de novo from the bottom-up with specialized functions, including chemokine secretion. Synthetic
cells are not alive, do not grow or divide, and may be a safer alternative to use in future in vivo applications.
Leveraging recent synthetic biology developments in engineered mammalian and synthetic cells, synthetic
cells with custom input-output relationship will be constructed. We will engineer synthetic cells to detect
local concentrations of a specific chemokine, allowing real-time monitoring of chemokine gradients. We also
will design synthetic cells that upon direct interaction with a living cell, respond by secreting a chemokine to
disrupt the chemotactic gradient presented to a living cell. These tools will enable us to understand how
local concentrations of a chemokine regulate signaling and movement of living cells. The proposed work
consists of two specific aims: 1) To develop synthetic cells that can report local chemokine concentrations;
and 2) To develop synthetic cells that modulate the chemokine environment to regulate chemotaxis. The
proposed research is significant as it applies established synthetic biology concepts in mammalian cells to
synthetic cells, filling a fundamental gap in tool development that has prevented complete understanding of
chemotaxis in complex environments. The work will also have a lasting impact that opens the door for
potential new interventions using engineered synthetic cells to manipulate local chemokine profiles
specifically and controllably for therapy in ...

## Key facts

- **NIH application ID:** 10911003
- **Project number:** 5R21AI173559-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Allen Po-Chih Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,000
- **Award type:** 5
- **Project period:** 2023-08-21 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10911003

## Citation

> US National Institutes of Health, RePORTER application 10911003, Sensing and modulating the chemokine environment with synthetic cells (5R21AI173559-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10911003. Licensed CC0.

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