# Design-driven engineering of robust mammalian sense-and-respond functions

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $346,428

## Abstract

Project Summary
 The ultimate goal of this project is to enable the use of engineered cell therapies to safely and
effectively treat conditions ranging from cancer, to autoimmune disease, to those requiring regenerative
medicine. Engineered cell therapies represent an exciting frontier in medicine, and early successes in the field
of cancer treatment have demonstrated the transformative potential of this approach, enabling the treatment of
patients for whom no existing therapy was effective. However, fully realizing the promise of engineered cell
therapies will require technologies and tools that enable bioengineers to efficiently design, build, and evaluate
customized cellular functions that meet specific clinical needs. While the field of mammalian synthetic biology
has made impressive strides toward this goal, translating basic science to the clinic imposes a new set of
design and engineering challenges. In particular, new experimental technologies and computational tools are
needed to design cell therapies in a way that leads to robust performance—the successful execution of a
therapeutic program despite inevitable biological variability.
 To meet this need, this team will develop an integrated suite of new experimental reagents, new
computational tools, and new conceptual understanding to accelerate the implementation of design-driven
medicine by enabling bioengineers to program cells to sense, evaluate, and respond to their environment in
novel, useful, and reliable ways. The team recently developed a synthetic biology technology called MESA
receptor proteins, which enable one to “rewire” how a cell senses features of host physiology. This project
comprises a crucial bridge from an early demonstration of a promising strategy to the development of a true
technology platform that may be readily applied by the bioengineering community to design and construct
novel cell therapies. The goals of this project are informed by the team's substantial experience in engineered
receptor technologies, and this project addresses general challenges in mammalian synthetic biology. The first
Aim is to develop strategies for engineering cellular sensing functions that perform robustly across inevitable
biological variation. This aim comprises computational model-guided design of proteins and genetic
components to make cellular sensing functions more useful for bioengineering. This work will include a
comparison of MESA with other engineered sensing platforms. The second Aim is to develop a library of novel
MESA biosensors that respond to physiologically relevant cues. Outcomes of this aim will include a better
understanding of how to build biosensors, as well as a panel of reagents that enable bioengineers to
immediately employ this technology for therapeutic applications. The third Aim is to evaluate and develop
strategies for implementing engineered biosensing functions in a wide range of cell types, including both stable
cell lines and primary cells, with ...

## Key facts

- **NIH application ID:** 10159736
- **Project number:** 5R01EB026510-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Joshua Nathaniel Leonard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $346,428
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159736

## Citation

> US National Institutes of Health, RePORTER application 10159736, Design-driven engineering of robust mammalian sense-and-respond functions (5R01EB026510-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10159736. Licensed CC0.

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