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Optogenetics protein engineering
My research focuses on employing light-regulated components in cell biology (Optogenetics). It has revolutionized the investigation and understanding of physiological processes. The outstanding advantage of using light over other inducing methods to control the initiation and modification of cellular events, lies in three remarkable features: i) light regulation is instantaneous and synchronous in the ON and OFF modes, ii) precise in spatial and temporal activation, and, most importantly, iii) steering of these processes occurs non-invasive. The basis for this research field is the use of naturally occurring biological photoreceptors that selectively initiate biological processes and reaction chains after capturing a photon. Though intracellular protein interactions have been reported and studied for a while, the ratio between well-understood and obscurely acting systems is unfortunately imbalanced. Often, natural systems also show certain leakiness, making precise regulation of processes under study complicated. Clearly, many features of these chromoproteins require optimization for their employment in cell biology and bio-medicine.
My research target is the engineering, optimization, and de-novo design of optogenetic tools for modern genetic applications, as well as elucidating so-far unknown metabolic pathways. We perform the rational design of proteins for new light-driven tools based on structural and biochemical data using AI methods. This is accompanied by in vivo prototyping, testing, and optimization of the new designs for applications in Fungi, plant, and mammalian cell lines, as well as primary cell cultures. Our work applies directed molecular evolution to naturally occurring photoreceptors and engineered protein modules, followed by systematic variation of protein modules and custom-designed screening and selection strategies. We can fine-tune naturally occurring proteins that interact with photoreceptors in the natural function of regulating physiological processes or design novel protein interactions from scratch. An example of such a de-novo design is the development of a light-selective binder for a cyanobacteriochrome (CBCR). CBCRs are photoreceptors available for nearly every visible light wavelength ranging from the near ultraviolet to the near-infra red range. This enables the combined application (multiplexing) of several photoreceptors, that respond to different individual wavelengths. Driven by this example, we aim to develop new opto-switches to enlarge the pool of available optogenetic tools to address so far unknown and unthought biological and medical problems.