Computational Design of Engineered Photoreceptors for Optogenetics Applications

The aim of this proposal is to combine the emerging fields of computational protein design (CPD) and optogenetics. The subject of CPD is the design of proteins with new functions. Optogenerics describes the control of biological processes by light. Underlying all optogenetics applications are a class of proteins called photoreceptors. Current attempts at designing artificial photoreceptors have relied on simple design approaches. By applying advanced computational methodology, in combination with high-throughput screening, we propose to extend optogenetics to target biological phenomena not accessible by current approaches. Specifically, we propose to use CPD alongside a fluorescent-reporter based high-throughput assay to create a heterodimeric version of a naturally occurring, homodimeric photoreceptor. This designed heterodimeric photoreceptor can then be used to render the activity of other heterodimeric effector proteins (i.e. G-proteins or transcription factors) light-sensitive. In particular, we will target G-protein signaling by using CPD to create fusions between the designed heterodimeric photoreceptor and the heterodimeric G beta/gamma subunit, which plays a central role in G-protein linked events. A yeast-display based selection scheme will be used to screen for fusions with light-dependent affinity for the Galpha subunit. If successful, this would lay the groundwork for triggering signaling processes in mammalian cells by light.

Principal Investigators
Möglich, Andreas Prof. Dr. (Details) (Biophysical Chemistry)

Duration of Project
Start date: 08/2013
End date: 07/2014

Last updated on 2020-25-11 at 15:07