# Systems Biology to Unlock the Next Level of Cell-Free Synthetic Biology

> **NIH NIH R35** · GEORGIA INSTITUTE OF TECHNOLOGY · 2023 · $395,500

## Abstract

Project Summary
Research in the PI’s laboratory focuses on metabolism, with applications in systems and synthetic
biology. The lab has two main goals: to study and model metabolic dynamics and regulation, and
to develop minimal-equipment biosensors for nutritional deficiencies for deployment to resource-
poor environments. The biosensor work has broad potential global utility and impact, and also
motivates some of the systems biology analyses they perform. Those metabolic studies lie at the
interface of computation and experiment, and are unified via their use of metabolomics. His group
uses temporal metabolomics measurements to capture the metabolic dynamics of biological
systems, and then uses these data for analysis, understanding, and engineering of those
biological systems. In parallel, they develop computational tools to better exploit metabolomics
data, with an aim towards applying those data to new metabolic modeling frameworks.
In the next five years, the PI will tackle some of the most significant yet understudied challenges
in cell-free systems, the group’s current platform of choice for the development of field-deployable
biosensors. In the past five years he has been a trailblazer at the interface of systems biology and
cell-free synthetic biology, discovering that residual endogenous metabolism in lysate-based cell-
free systems is critical in determining the total productivity of a given reaction. He will expand
upon that discovery to fully characterize the impacts of endogenous metabolism on cell-free
systems, and to move towards solving what is currently the key challenge to broader adoption
and use of cell-free systems: early termination of expression in reactions. He will use a host of
systems-scale tools, including metabolomics, proteomics, and fluxomics, to create a
comprehensive (and the only) systems-scale characterization of metabolism in cell-free systems,
and will complement these efforts with metabolic modeling and analysis to gain greater insight
into the inner workings of the system.
The PI’s overall vision is of a deeper understanding of cell-free systems that allows them to go to
the next level in terms of adoption, applications, and impact. He also envisions significant
biological insight coming from these cell-derived but cell-free systems, including the ability to
discover regulatory interactions that might otherwise be masked by epistatic effects in vivo. He
envisions the results of his work being exploited by biologists and bioengineers to enable more
effective in vitro models of biological systems as well as biotechnological advances that were
previously either scientifically or economically infeasible.

## Key facts

- **NIH application ID:** 10623894
- **Project number:** 1R35GM149286-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Mark Philip-Walter Styczynski
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $395,500
- **Award type:** 1
- **Project period:** 2023-09-06 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10623894

## Citation

> US National Institutes of Health, RePORTER application 10623894, Systems Biology to Unlock the Next Level of Cell-Free Synthetic Biology (1R35GM149286-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10623894. Licensed CC0.

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