- Denard and Jang will engineer asymmetric, protein‑based vesicles that mimic cellular signal transduction.
- Funded by NSF, this work aims to create programmable synthetic cells for biosensing and drug delivery.
- The project seeks precise control over membrane orientation and signaling pathways.
Powered by a recent grant, two University of Florida researchers are addressing a long-standing challenge in synthetic biology and potentially establishing new design principles for programmable synthetic cells.
Over the next three years, Carl Denard, Ph.D., and Yeongseon Jang, Ph.D., — assistant professors in the Department of Chemical Engineering, known as ChE — will collaborate on the project “Recombinant Bolaamphiphilic Protein Engineering for Asymmetric Vesicle Formation: Toward Synthetic Cell Signal Transduction.” The work is funded by the National Science Foundation, or NSF.
Simply put, they plan to re-create how living cells sense and respond to their environments in programmable synthetic systems by creating synthetic membranes with controlled asymmetry and directional signaling.
Transmembrane signal transduction is a fundamental mechanism in all living cells, Denard said.
A useful analogy: Think of a cell as a smart home. Sensors on the outside detect what is happening, and the internal system processes the information and decides how to respond. Denard and Jang are developing simplified, programmable versions of a home’s “sense and respond system” by using engineered proteins.
“With this grant, we will investigate how to replicate this function in rationally designed, protein-based vesicles. We will endow these synthetic mimetics with a variety of sensing and actuation functions in a plug-and-play fashion,” Denard said.
“If successful,” he added, “these highly functionalized protein vesicles will establish new design rules for constructing cell-like protein biomaterials and embedding cell functions in synthetic mimetics, push the boundaries of self-assembling protein vesicles and advance new applications in biosensing, drug delivery and responsive systems.”
Denard and Jang’s goal stems from a simple jumping-off point: Living cells process information through highly organized membranes and signaling networks.
Jang’s laboratory has developed many research theories by simply asking how nature solves problems at the molecular level. That same question served them well on this project, too.
“After demonstrating that synthetic protein vesicles could sense external signals, we became interested in re-creating the next level of cellular complexity — how cells process information and convert it into functional responses,” said Jang, ChE’s Alex Moreno Rising Star Professor.
Jang’s laboratory previously developed fully protein-based vesicles that can self-assemble and perform simple sensing functions.
“Those discoveries demonstrated the feasibility of synthetic cell-like systems and inspired us to explore more sophisticated capabilities, including directional signal transduction and membrane asymmetry,” Jang said.
Her collaboration with Denard’s lab enabled them to integrate protein engineering with synthetic cell design, providing the foundation for the project.
“The innovation lies in creating fully recombinant protein vesicles with built-in membrane asymmetry and programmable signal transduction,” Jang said. “Unlike traditional lipid-based systems, these protein-based structures offer precise control over protein organization, orientation and function,” she added.