# Integrative Circuit-Host Modeling of Synthetic Gene Networks

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $382,218

## Abstract

Abstract
Quantitative modeling of gene circuits is fundamentally important to synthetic biology, as it offers the potential
to transform circuit engineering from trial-and-error construction to rational design and, hence, facilitates the
advance of the ﬁeld. Currently, typical models regard gene circuits as isolated entities and focus only on the
biochemical processes within the circuits. Although highly valuable, such a `standard' paradigm has shown to
be often incapable of quantitatively, or sometimes even qualitatively, describing circuit behaviors. This limitation
arises from multiple factors, among which the overlook of the intimate coupling between circuits and their host
is a major cause. My research program aims to discover the fundamental design principles of bacterial gene
circuits by harnessing the power of math-based reasoning and tight integration of experiment with theory. In this
project, we plan to develop an integrative modeling framework that quantitatively describes gene circuit behaviors
in the context of bidirectional circuit-host coupling across multiple scales. To achieve our goal, we will employ
a multidisciplinary approach that combines mathematical modeling and experimental molecular biology. We will
also build our research on our recent success in the creation of a promising preliminary circuit-host model. For
the next few years, our research is organized into three separate but interconnected themes: (1) Develop a
generalized framework of circuit-host resource allocation, (2) Build a capacity to account for circuits in varying
environments, and (3) Establish a understanding of gene circuit behaviors in ecological contexts. These themes of
research will involve the development of generalized theoretical foundations (Theme 1) as well as the investigation
of speciﬁc key challenges relating to future real-world applications (Theme 2 and 3). The proposed work promises
to yield an integrative mathematical framework that quantitatively describes and predicts circuit behaviors with
the incorporation of host physiology and circuit-host coupling across multiple scales. Such a framework will help
to shift the paradigms of gene circuit engineering from trial-and-error creation to rational design and forward
engineering. Additionally, it will advance our understanding of the regulatory dynamics underlying bacterial gene
networks and also offer quantitative insights into complex bacterial physiology.

## Key facts

- **NIH application ID:** 10178046
- **Project number:** 5R35GM133579-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Ting Lu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,218
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178046

## Citation

> US National Institutes of Health, RePORTER application 10178046, Integrative Circuit-Host Modeling of Synthetic Gene Networks (5R35GM133579-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10178046. Licensed CC0.

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