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ESBS - Strasbourg

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Synthetic Photoreceptors:

The use and design of Synthetic Photoreceptors is a promising approach in Synthetic Biology, as light is an ideal tool to gain spatiotemporal control of biological processes.

Photoreceptors respond to light absorption with a change in biological activity that elicits a physiological response. Since the biological activity of photoreceptors is light-dependent, light can be used to control their function and thus the behavior of entire cells and organisms in which they are expressed. The identification, understanding and following application of fluorescent proteins have been a revolution in molecular biology due to the improved ability to MONITOR cellular processes. In great contrast, the application of photoreceptors allows us even to CONTROL cellular behavior by light.

There are six different classes of photoreceptors distinguished by their chromophores and photochemistry: light-oxygen-voltage (LOV) sensors, xanthopsins, phytochromes, blue-light sensors using flavin adenine dinucleotide (BLUF), cryptochromes, and rhodopsins. The two classes which are currently most widely used in the design of engineered photoreceptors are LOV domains and phytochromes (Möglich & Moffath, 2010).

The first in vivo applications of natural photoreceptors were in the domain of neurosciences using the light-sensitive cation channel channelrhodopsin. The reason for the great success was probably that it can be genetically encoded and expressed in the desired location, affording non-invasive and reversible control over neural processes with high spatiotemporal resolution. The new generation of recently developed engineered photoreceptors now extends the repertoire of light-regulated tools. Phytochromes are especially attractive for biological applications because they respond to changes in the red and far-red region of the electromagnetic spectrum; wavelengths that are well tolerated by biological systems and that have good tissue penetrance.

Based on the properties and architecture of natural photoreceptors, artificially photoreceptors with novel light-regulated functions have been successfully designed and used to control molecular activity and cellular behavior. There have been various examples for the artificially designed systems based on the implementation of naturally occurring light-sensitive domain or the use of semi-synthetic photoactive allosteric modulators.

In Synthetic Biology there is a special interest of coupling the activity of targeted proteins to light signals. Synthetic photoreceptor interaction modules can be integrated in genetic circuits enlarging the power and accessibility of tool sets and methods available in this emerging field. Because of their generic nature engineered photoreceptors can be used to control a broad range of biological processes in intact cells and organism. The high spatial and temporal resolution and non-invasiveness of light control allows the construction of new analytical tools. Levskaya et. al (2009) demonstrated an application of such a tool to visualize cell shape at a high resolution.

An improved mechanistic understanding of different, natural photoreceptor classes and the work on further examples of engineered photoreceptors will provide an improved basis for the design and application of novel groundbreaking synthetic photoreceptors.

The possibility to render any arbitrary biological functionality, especially in mammalian cells, light-dependent would extend their present applications as clever tool in cell biology to a clinical standard module. This design of such a synthetic light-gated module is an appealing future objective in Synthetic Biology, as the use of such a device would present a general approach without the need for time-consuming case-by-case engineering.