# Design-driven engineering of robust mammalian sense-and-respond functions: from parts to programs

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2023 · $615,361

## Abstract

Project Summary
 The overarching goal of this project is to enable the use of engineered cell therapies to safely and effectively
treat conditions ranging across cancer, autoimmune disease, and regenerative medicine. Engineered cell
therapies are an exciting frontier, with early successes in cancer treatment demonstrating the transformative
potential of this approach. Customized cell therapies could yield safe and effective treatments for many
applications beyond cancer, but realizing this potential is limited by the fact that evaluating a potential therapeutic
strategy requires extensive time and resources to implement it. The goal of this project is to flip this paradigm—
to enable spending less time building and thus focus on evaluating potentially useful strategies.
 This project will develop state-of-the-art technologies for cell engineering and enable their application to solve
three open, complementary, clinically motivated challenges. The first aim is to develop the technology,
understanding, and computational tools required to build genetic programs that employ natural mechanisms for
implementing long-lived memory. Natural systems employ genetic memory to drive processes such as
differentiation and development by adding and removing stable marks to the genome. Although research has
yielded insights into how to drive such changes, bioengineers do not yet have the ability to leverage those
insights to build programs that implement these effects for useful purposes. This project will address this need
by developing genetic programs that exhibit stable behaviors including inducible and autonomous state
switching. The second aim will generate novel candidate cell therapies for treating cancer that leverage
foundational advances for engineering cells to evaluate and respond to external cues (e.g., unique markers of
the tumor site) to induce desired therapeutic behaviors. This work will develop programs hypothesized to improve
both safety and efficacy of these approaches. A key aspect of this work is employing model-guided design to
evaluate and refine genetic programs to confer desired behaviors. The third aim will develop a computational
framework enabling computer-assisted design of genetic programs. Current design is limited by the imagination
of the designer—a human must propose a design which is subsequently evaluated. This aim will make the
transformative leap to semi-automated design, establishing workflows and tools that are freely accessible to
researchers in a graphics-enabled open software framework.

## Key facts

- **NIH application ID:** 10682086
- **Project number:** 2R01EB026510-05A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Neda Bagheri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $615,361
- **Award type:** 2
- **Project period:** 2018-08-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10682086

## Citation

> US National Institutes of Health, RePORTER application 10682086, Design-driven engineering of robust mammalian sense-and-respond functions: from parts to programs (2R01EB026510-05A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10682086. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*