Photoactive proteins
Nature has built fantastic light-activated proteins to control, for example, photosynthesis, plant physiology, and animal vision. Furthermore, in recent decades, photoactive proteins have found immense use as light-responsive tools for basic science and biotechnology, incl. fluorescent proteins, optogenetic actuators, and photobiocatalysts. Almost all these tools have been engineered from natural proteins. Thus, our understanding of photoactive proteins largely relates to specific natural protein folds. However, there are many challenges of modern society that natural evolution has never been tasked to solve.
In our research, we aim to advance our ability to create artificial photoactive proteins with folds and functions beyond those in nature. Using chromophores as model cofactors, the project will explore, develop, and validate methods for de novo design of cofactor-binding proteins. In this process, we develop protein design principles and protocols as well as new protein modules for synthetic/chemical biology tools such as biosensors for fluorescence microscopy.
Chemoswitchable binders
Unbalanced immune signaling has been coupled to several brain diseases, but our understanding of the underlying biochemical signals is limited. To map the complex biochemical signals, molecular tools for interrupting and monitoring the signals in cell cultures and research animals can be used – but our current tools are limited in their ability to decipher exactly when and where the signals are important.
We are developing a new and generalizable protein-based tool (chemoswitchable binders), that consists of two fused protein modules: an inhibitor module, that binds specifically to a natural protein target, and a switch module, that can be activated by a small ligand molecule. Our goal is to create a precision tool that can be activated to interrupt a biochemical signal anywhere in the body of a research animal, including the brain. We are focusing on developing the tool for studying neuroimmunology, including gut-brain signaling and neurooncology.
Funding
The group is currently funded by two starting grants: 1) A Villum Young Investigator project on de novo design of photoactive proteins, and 2) A DFF Sapere Aude project on the computational design and experimental validation of Chemoswitchable binders for probing endogenous cell signaling.