Project description
Tuneable protein properties via functional insertions
Synthetic biology uses engineering principles to design or redesign bioactive molecules and systems to produce novel functions that can solve important challenges in medicine, agriculture and society. Proteins are the workhorses of biological systems. Their function is intricately regulated by other molecules or environmental conditions. The ERC-funded PROFI project aims to develop a platform enabling insertion into proteins of tuneable building blocks to create proteins and biological systems that respond to biological, chemical and physical signals in controlled ways. The ability to engineer proteins with unique and previously unknown properties will pave the way to new therapeutic applications. The platform’s potential will be demonstrated in mammalian cells.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticsRNA
- medical and health sciencesbasic medicineimmunologyimmunotherapy
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Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
1000 Ljubljana
Slovenia