Generic protein tool for the fast and reversible inactivation of proteins using light

The field of tissue engineering aims to create functional human tissues from cells to repair or replace diseased or damaged tissues and organs. An important requirement for the field to proceed is to activate or inhibit signalling pathways at specific locations and during precise time windows. However, the field currently lacks general tools to control the activity of proteins and pathways in a position and time resolved manner. A promising solution for this problem is the use of light to control protein activity. Light has many advantages over, for example chemical inducers, because it is fast, inexpensive, non-toxic and extremely precise. In this project, the aim is to develop a general light-inducible protein tool that can provide reversible, rapid and non-toxic control over the activity of proteins. The proposed light-switchable tool will first be optimized in the yeast species S. cerevisiae, because in this organism constructs can be introduced and screened quickly, cheaply and efficiently. Next, the tool will be introduced in the model organism C. elegans, which is a small transparent worm, to demonstrate the performance of the tool in a multicellular system. Wnt pathway proteins will be perturbed at precise moments of the embryonic development and in specific cells. Control on Wnt signalling is of great importance for tissue engineering due to its central role in guiding the formation of many tissues.