# Engineering mammalian gene activity sensor-actuator devices

> **NIH NIH R01** · RICE UNIVERSITY · 2021 · $339,400

## Abstract

Engineering mammalian gene activity sensors-actuator devices
Cellular devices that generate user-defined outputs in response to environmental cues hold unprecedented
opportunities for modern medicine through the development of living designer systems that detect and correct human
pathologies. These sensor-actuator devices are currently based on cell surface sensing capabilities, mostly achieved
by rewiring native ligand-receptor interactions or evolving non-native receptors linked to signal transduction systems.
The performance of receptor-based sensors depends ultimately on the signal transduction mechanism embedded in
the receptor system, however, and may not accurately recapitulate the physiologic response to the biomarker input.
Cellular physiological states are determined by complex mechanisms that integrate signals associated with different
quantitative features of extracellular and intracellular cues and provide blueprints to regulate the levels, states, and
dynamics of gene expression. Regulation of gene expression thus ultimately determines cell functionality during
physiological and pathological processes and is constantly and dynamically modulated to respond to environmental
as well as intracellular stimuli. We thus envisioned a novel class of cellular devices that actuate user-defined
biomolecular programs in response to the detection of the device’s physiological state achieved through real-time
monitoring of the activity of chromosomal genes. These gene activity sensor-actuator devices are based on innovative
tools recently developed by our groups for designing orthogonal systems that (i) link output expression to
chromosomal genes, thereby recapitulating complex mammalian regulatory processes with high fidelity, and (ii)
amplify the signal output with high resolution of the input dynamics, thereby recapitulating dynamic behaviors with
superior sensitivity.
To generate robust sensor-actuator devices that translate detection of gene expression signatures into user-defined
outputs, we will explore the design rules of sense-and-respond mechanisms for linking detection of gene activity to
output production (Aim 1), translate gene activity into precisely modulated delays in output production (Aim 2), self-
adjust output production in response to output-induced modulation of gene activity (Aim 3).
This approach is expected to create a paradigm shift in the way we design cellular devices that sense and respond to
the environment, as it will provide a strategy to engineer cells to sense virtually any cellular process associated with a
transcriptional response, eliminating the need to rewire ligand-receptor interactions or evolve synthetic receptor-based
devices. Results from this study will generate design rules of cellular devices that sense gene activity with high
dynamic resolution, enabling the development of cell-based diagnostics and therapeutics for a diverse range of
applications.

## Key facts

- **NIH application ID:** 10211197
- **Project number:** 1R01EB030030-01A1
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Laura Segatori
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $339,400
- **Award type:** 1
- **Project period:** 2021-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10211197

## Citation

> US National Institutes of Health, RePORTER application 10211197, Engineering mammalian gene activity sensor-actuator devices (1R01EB030030-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10211197. Licensed CC0.

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