The ability to control protein functionality with light has enormous potential to advance our understanding of biological problems and for use in biotechnology.  The most widely used applications to date include the ontogenetic systems, which enable neuronal action potentials to be regulated non-invasively with lasers; and various tools to induce protein dimerization with light.  These tools employ naturally occurring light sensing proteins/domains from plants and other organisms including Light, Oxygen,Voltage domain (LOV), phytochrome B(PHYB), Cryptochrome 2 protein (CRY2) and Dronpa. These proteins undergo large conformational changes or changes in the oligomeric state in the light state relative to the dark state.  In this project, we seek to build new light-activated proteins for use as tools in the lab and in medicine.  Starting with a transposon-based approach to randomly insert the LOV2 domain into our target proteins, we will screen for variants that display light-sensitive functionality.  The targets include firstly avidin, which is one of the most useful molecular biology and biotechnology tools because of its extraordinary binding affinity to biotin (K_d =10⁻¹⁴ M); the BirA biotin ligase, which is emerging as an exciting new proteomics tool for localization-specific biotinylation in cells and the barnase ribonuclease: barstar inhibitor complex, which if we can control barnase ribonuclease activity with light sensitive domains, will offer potential as a cancer cell killer triggered with light.