Showing 1 - 3 of 3 results
1.
Optogenetically controlled protein kinases for regulation of cellular signaling.
Abstract:
Protein kinases are involved in the regulation of many cellular processes including cell differentiation, survival, migration, axon guidance and neuronal plasticity. A growing set of optogenetic tools, termed opto-kinases, allows activation and inhibition of different protein kinases with light. The optogenetic regulation enables fast, reversible and non-invasive manipulation of protein kinase activities, complementing traditional methods, such as treatment with growth factors, protein kinase inhibitors or chemical dimerizers. In this review, we summarize the properties of the existing optogenetic tools for controlling tyrosine kinases and serine-threonine kinases. We discuss how the opto-kinases can be applied for studies of spatial and temporal aspects of protein kinase signaling in cells and organisms. We compare approaches for chemical and optogenetic regulation of protein kinase activity and present guidelines for selection of opto-kinases and equipment to control them with light. We also describe strategies to engineer novel opto-kinases on the basis of various photoreceptors.
2.
Engineering of bacterial phytochromes for near-infrared imaging, sensing, and light-control in mammals.
Abstract:
Near-infrared light is favourable for imaging in mammalian tissues due to low absorbance of hemoglobin, melanin, and water. Therefore, fluorescent proteins, biosensors and optogenetic constructs for optimal imaging, optical readout and light manipulation in mammals should have fluorescence and action spectra within the near-infrared window. Interestingly, natural Bacterial Phytochrome Photoreceptors (BphPs) utilize the low molecular weight biliverdin, found in most mammalian tissues, as a photoreactive chromophore. Due to their near-infrared absorbance BphPs are preferred templates for designing optical molecular tools for applications in mammals. Moreover, BphPs spectrally complement existing genetically-encoded probes. Several BphPs were already developed into the near-infrared fluorescent variants. Based on the analysis of the photochemistry and structure of BphPs we suggest a variety of possible BphP-based fluorescent proteins, biosensors, and optogenetic tools. Putative design strategies and experimental considerations for such probes are discussed.
3.
Synthetic mammalian gene networks as a blueprint for the design of interactive biohybrid materials.
Abstract:
Synthetic biology aims at the rational design and construction of devices, systems and organisms with desired functionality based on modular well-characterized biological building blocks. Based on first proof-of-concept studies in bacteria a decade ago, synthetic biology strategies have rapidly entered mammalian cell technology providing novel therapeutic solutions. Here we review how biological building blocks can be rewired to interactive regulatory genetic networks in mammalian cells and how these networks can be transformed into open- and closed-loop control configurations for autonomously managing disease phenotypes. In the second part of this tutorial review we describe how the regulatory biological sensors and switches can be transferred from mammalian cell synthetic biology to materials sciences in order to develop interactive biohybrid materials with similar (therapeutic) functionality as their synthetic biological archetypes. We develop a perspective of how the convergence of synthetic biology with materials sciences might contribute to the development of truly interactive and adaptive materials for autonomous operation in a complex environment.
