- Light effects on plants
- Photoreceptor and optogenetics research
- Photosynthetic Processes and Mechanisms
- 3D Printing in Biomedical Research
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Origins and Evolution of Life
- Transgenic Plants and Applications
- Virus-based gene therapy research
- Plant Molecular Biology Research
- Cellular Mechanics and Interactions
- bioluminescence and chemiluminescence research
- Photochromic and Fluorescence Chemistry
- Gene Regulatory Network Analysis
- RNA Interference and Gene Delivery
- Plant and Biological Electrophysiology Studies
- Pancreatic function and diabetes
- CAR-T cell therapy research
- Circadian rhythm and melatonin
- Viral Infectious Diseases and Gene Expression in Insects
- Pluripotent Stem Cells Research
- Supramolecular Self-Assembly in Materials
- Ion channel regulation and function
- Single-cell and spatial transcriptomics
- Hippo pathway signaling and YAP/TAZ
University of Freiburg
2014-2024
Massachusetts Institute of Technology
2019
Faculty (United Kingdom)
2014
German Cancer Research Center
2013
Heidelberg University
2013
Max Planck Society
2010
Max Planck Institute for Medical Research
2010
University of Nevada, Reno
1993
Engineering liquid-liquid phase separation into synthetic and optogenetic transcription factors increases gene expression.
Abstract Interrogation and control of cellular fate function using optogenetics is providing revolutionary insights into biology. Optogenetic cells achieved by coupling genetically encoded photoreceptors to effectors enables unprecedented spatiotemporal signaling processes. Here, a fast reversibly switchable photoreceptor used tune the mechanical properties polymer materials in fully reversible, wavelength‐specific, dose‐ space‐controlled manner. By integrating engineered cyanobacterial...
The immune system distinguishes between self and foreign antigens. kinetic proofreading (KPR) model proposes that T cells discriminate from ligands by the different ligand binding half-lives to cell receptor (TCR). It is challenging test KPR as available experimental systems fall short of only altering keeping other parameters interaction unchanged. We engineered an optogenetic using plant photoreceptor phytochrome B (PhyB) a selectively control dynamics TCR light. This opto-ligand-TCR was...
Abstract The fundamental life-defining processes in living cells, such as replication, division, adaptation, and tissue formation, occur via intertwined metabolic reaction networks that process signals for downstream effects with high precision a confined, crowded environment. Hence, it is crucial to understand reenact some of these functions wholly synthetic cell-like entities (protocells) envision designing soft materials life-like traits. Herein, we report on all-DNA protocells composed...
Optogenetics is a versatile and powerful tool for the control analysis of cellular signaling processes. The activation receptors by light using optogenetic switches usually requires genetic manipulation cells. However, this considerably limits application in primary, nonengineered cells, which crucial study physiological processes controlling cell fate function therapeutic purposes. To overcome limitation, we developed system light-dependent extracellular surface cells termed OptoREACT...
Optogenetic approaches have gathered momentum in precisely modulating and interrogating cellular signalling gene expression. The use of optogenetics on the outer cell surface to interrogate how cells receive stimuli from their environment, however, has so far not reached its full potential. Here we demonstrate development an optogenetically regulated membrane receptor-ligand pair exemplified by optically responsive interaction integrin receptor with extracellular matrix. system is based...
Methodologies for the controlled delivery of genetic information into target cells are utmost importance engineering in both fundamental and applied research. However, available methods efficient gene transfer user-selected or even single suffer from low throughput, need complicated equipment, high invasiveness, side effects by off-target viral uptake. Here, we engineer an adeno-associated (AAV) vector system that transfers native upon illumination with cell-compatible red light. This...
Abstract Hydrogels with adjustable mechanical properties have been engineered as matrices for mammalian cells and allow the dynamic, mechano‐responsive manipulation of cell fate function. Recent research yields hydrogels, where biological photoreceptors translated optical signals into a reversible change in hydrogel mechanics. While their initial application provides important insights mechanobiology, broader implementation is limited by small dynamic range addressable stiffness. Herein,...
Abstract Synthetic biology applies engineering concepts to build cellular systems that perceive and process information. This is achieved by assembling genetic modules according design principles. Recent advance in the field has contributed optogenetic switches for controlling diverse biological functions response light. Here, concept introduced apply synthetic principles synthesis of multi‐input‐processing materials. exemplified a materials system counts light pulses. Guided quantitative...
Transcription termination of non-polyadenylated RNAs in Saccharomyces cerevisiae occurs through the action Nrd1–Nab3–Sen1 complex. Part decision to terminate via this pathway direct recognition sequences within nascent transcript by RNA motifs (RRMs) Nrd1 and Nab3. Here we present 1.6 Å structure Nab3-RRM bound its UCUU sequence. The crystal reveals clear density for a UCU trinucleotide fourth putative U binding site. establishes preference central cytidine motif, which forms pseudo-base...
Summary Phytochromes (phy) C, D and E are involved in the regulation of red/far‐red light‐induced photomorphogenesis Arabidopsis thaliana, but only limited data available on mode action biological function these lesser studied phytochrome species. We fused N‐terminal fragments or full‐length PHYC, to YELLOW FLUORESCENT PROTEIN ( YFP ), analyzed function, stability intracellular distribution fusion proteins planta . The activity constitutively nuclear‐localized homodimers was comparable with...
Obtaining accurate estimates of biological or enzymatic reaction rates is critical in understanding the design principles a network and how processes can be experimentally manipulated on demand. In many cases experimental limitations mean that some cannot measured directly, requiring mathematical algorithms to estimate them. Here, we describe methodology calculates at which light-regulated proteins switch between conformational states. We focus our analysis phytochrome family photoreceptors...
Phytochromes are important photoreceptors of plants, bacteria, and fungi responsive to light in the red far-red spectrum. For increasing applications basic research, synthetic biology, materials sciences, it is required recombinantly produce purify phytochromes high amounts. An ideal host organism for this purpose E. coli due its widespread use, fast growth, ability high-cell-density fermentation. Here, we describe development a generic platform production that compatible with We exemplify...
Abstract In the rapidly expanding field of molecular optogenetics, performance engineered systems relies on switching properties underlying genetically encoded photoreceptors. this study, bacterial phytochromes Cph1 and Dr BphP are engineered, recombinantly produced in Escherichia coli , characterized regarding their order to synthesize biohybrid hydrogels with increased light‐responsive stiffness modulations. The R472A mutant cyanobacterial phytochrome 1 (Cph1) is identified confer...
Multiprotein complexes control the behavior of cells, such as lymphocytes immune system. Methods to affinity purify protein and determine their interactome by mass spectrometry are thus widely used. One drawback these methods is presence false positives. In fact, elution interest (POI) done changing biochemical properties buffer, so that unspecifically bound proteins (the positives) may also elute. Here, we developed an optogenetics-derived light-controlled purification method based on...
Fibrosis is associated with aging and many cardiac pathologies. It characterized both by myofibroblast differentiation excessive accumulation of extracellular matrix proteins. Fibrosis-related tissue remodeling results in significant changes structure function, including passive mechanical properties. This research area has gained momentum the recent development new tools approaches to better characterize understand ability cells sense respond their biophysical environment. We use a novel...
We have developed and characterized an organ culture system that maintains the viability of colonic smooth muscles. Morphological, mechanical, electrical, molecular properties cultured canine circular muscles were determined. Strips muscle for up to 6 days. The phenotype was retained during culture; contracted agonists responded electrical field stimulation, suggesting intrinsic nerves also survived in culture. Morphological analysis showed identifiable cells, enteric neurons, interstitial...
In the field of extracellular optogenetics, photoreceptors are applied outside cells to obtain systems with a desired functionality. Among diverse photoreceptors, phytochromes only ones that can be actively and reversibly switched between active inactive photostate by illumination cell-compatible red far-red light. this protocol, we describe production biotinylated variant photosensory domain A. thaliana phytochrome B (PhyB-AviTag) in E. coli single, optimized expression plasmid. We give...