Protein function regulation through inserts for response to biological, chemical and physical signals

We live in an era of profound excitement for synthetic biology, which is providing insights into the underlying mechanisms of living systems and powerful tools to modify biological and biomimetic systems using innovative design principles.

Regulation of protein function based on the recognition of other molecules or environmental conditions is fundamental to all living systems.

My vision and the strategic objectives of the project are to develop a modular platform that imparts proteins with the ability to sense diverse signals, thus enabling the regulation of their function and the introduction of novel properties into biological systems.

This project aims to explore unique opportunities for regulating protein function through insertions, leveraging modular building blocks with well-known and tunable properties.

By combining these building blocks in innovative ways, proteins and biological systems will be engineered to respond to biological, chemical, and physical signals.

The specific objectives of the project encompass: 1) design protein responsiveness to pH and RNA molecules, generating RNA sensors and regulating protein function based on cell type- or state-specific RNA molecules; 2) enable proteins to sense the concentration of other proteins, creating concentration-dependent regulatory circuits with a demonstration of biomedical application; 3) construct de novo mechano-responsive proteins, to prepare genetically encoded mechanosensors tolerant to high forces and mechanoresponsive designs of CAR for cancer immunotherapy and 4), design new protein regulators with favorable in vivo properties and regulators of natural proteins.

Through several compelling examples in mammalian cells, this project aims to demonstrate the transformative potential of endowing proteins with unique and previously unknown properties, advancing the engineering of biological systems and paving the way for potential therapeutic applications in the field of biomedicine.