A5074413118- Photoreceptor and optogenetics research
- Photochromic and Fluorescence Chemistry
- Neuroscience and Neuropharmacology Research
- Retinal Development and Disorders
- Protein Structure and Dynamics
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Molecular Sensors and Ion Detection
- Enzyme Structure and Function
- Spectroscopy and Quantum Chemical Studies
- DNA and Nucleic Acid Chemistry
- Neural dynamics and brain function
- RNA and protein synthesis mechanisms
- Nicotinic Acetylcholine Receptors Study
- Graphene and Nanomaterials Applications
- Advanced Fluorescence Microscopy Techniques
- Advanced Chemical Sensor Technologies
- Neuroinflammation and Neurodegeneration Mechanisms
- Memory and Neural Mechanisms
- Chemical Synthesis and Analysis
- Neurotransmitter Receptor Influence on Behavior
- Light effects on plants
- Heat Transfer and Optimization
- Diet and metabolism studies
- Click Chemistry and Applications
Ruhr University Bochum
2016-2025
Karlsruhe Institute of Technology
2017
University of California, Berkeley
2011-2016
University of California System
2014
Berkeley College
2013-2014
Center for Integrated Protein Science Munich
2009-2013
Technical University of Munich
2008-2013
Max Planck Research Unit for Enzymology of Protein Folding
2008
Urbana University
1985
University of Illinois Urbana-Champaign
1985
The use of azobenzene photoswitches has become a dependable method for rapid and exact modulation biological processes material science systems. requirement ultraviolet light isomerization is not ideal systems due to poor tissue penetration potentially damaging effects. While modified cores with red-shifted cis-to-trans have been previously described, they yet incorporated into powerful control protein function: the photoswitchable tethered ligand (PTL) approach. We report synthesis...
Neurotransmitters are important signaling molecules in the brain and relevant many diseases. Measuring them with high spatial temporal resolutions biological systems is challenging. Here, we develop a ratiometric fluorescent sensor/probe for catecholamine neurotransmitters on basis of near-infrared (NIR) semiconducting single wall carbon nanotubes (SWCNTs). Phenylboronic acid (PBA)-based quantum defects incorporated into to interact selectively catechol moieties. These PBA-SWCNTs further...
Significance We restored visual function to animal models of human blindness using a chemical compound that photosensitizes mammalian ion channel. Virus-mediated expression this light sensor in surviving retinal cells blind mice responses vitro, reanimated innate avoidance, and enabled learned visually guided behavior. The treatment also the retina dogs. Patients might benefit from would need have intact ganglion cell nerve fiber layers. In general, these are patients diagnosed with...
A tetra-ortho-chloro substituted azobenzene unit was incorporated into a photoswitchable tethered ligand for ionotropic glutamate receptors. This compound confers the modified protein with unusual optical responses of azo scaffold permitting channel opening yellow and red light closing blue light.
A reversible structural unlocking reaction, in which the close-packed van der Waals interactions break cooperatively, has been found for villin headpiece subdomain (HP35) using triplet-triplet-energy transfer to monitor conformational fluctuations from equilibrium. Unlocking is associated with an unfavorable enthalpy change (Δ H 0 = 35 ± 4 kJ/mol) nearly compensated free energy by entropy S 112 20 J·mol -1 ·K ). The reaction a time constant of about 1 μs at 5 °C and enthalpy-limited...
NMDA receptors, which regulate synaptic strength and are implicated in learning memory, consist of several subtypes with distinct subunit compositions functional properties. To enable spatiotemporally defined, rapid reproducible manipulation function specific subtypes, we engineered a set photoswitchable GluN subunits ('LiGluNs'). Photo-agonism GluN2A or GluN2B elicits an excitatory drive to hippocampal neurons that can be shaped time mimic activation. at single dendritic spines evokes...
We developed a family of genetically encoded serotonin (5-HT) sensors (sDarken) on the basis native 5-HT1A receptor and circularly permuted GFP. sDarken 5-HT are bright in unbound state diminish their fluorescence upon binding 5-HT. Sensor variants with different affinities for were engineered to increase versatility imaging dynamics. Experiments vitro vivo showed feasibility dynamics high temporal spatial resolution. As demonstrated here, designed show excellent membrane expression, have...
Thioxoamide (thioamide) bonds are nearly isosteric substitutions for amides but have altered hydrogen-bonding and photophysical properties. They thus well-suited backbone modifications physicochemical studies on peptides proteins. The effect of thioxoamides protein structure stability has not been subject to detailed experimental investigations up date. We used alanine-based model test the influence single thioxoamide alpha-helix stability. results from circular dichroism measurements show...
Coupling fast triplet-triplet energy transfer (TTET) between xanthone and naphthylalanine to the helix-coil equilibrium in alanine-based peptides allowed observation of local fluctuations alpha-helices on nanoseconds microseconds time scale. The experiments revealed faster helix unfolding terminal regions compared with central parts constants varying from 250 ns 1.4 micros at 5 degrees C. Local formation occurs a constant approximately 400 ns, independent position helix. Comparing...
The ability to optically manipulate specific neuronal signaling proteins with genetic precision paves the way for dissection of their roles in brain function, behavior, and disease. Chemical optogenetic control photoswitchable tethered ligands (PTLs) enables rapid, reversible reproducible activation or block neurotransmitter-gated receptors ion channels cells. In this study, we further engineered characterized light-activated GluK2 kainate receptor, LiGluR, develop a toolbox LiGluR variants....
Abstract Ionotropic glutamate receptors (iGluRs) play key roles for signaling in the central nervous system. Alternative splicing and RNA editing are well-known mechanisms to increase iGluR diversity provide context-dependent regulation. Earlier work on isoform identification has focused analysis of cloned transcripts, mostly from rodents. We here set out obtain a systematic overview human brain based RNA-Seq data. Using data two large-scale transcriptome studies, we established workflow de...
The kainate receptors (KARs) are members of the ionotropic glutamate receptor family and assemble into tetramers from a pool five subunit types (GluK1-5). Each confers distinct functional properties to receptor, but compositional stoichiometric diversity KAR is not well understood. To address this, we first solve structure GluK1 homomer, which enables systematic assessment structural compatibility among subunits. Next, analyze single-cell RNA sequencing data, reveal extreme in combinations...
Neural glutamate homeostasis plays a key role in health and disease. In ischemic conditions, such as stroke, this is severely disrupted since energy depletion ion imbalances lead to more release less uptake. We here used the fluorescent sensor SF iGluSnFR(A184V) probe effects of chemical ischemia on extracellular dynamics situ, using organotypic slice cultures from mouse cortex. iGluSnFR imaging reported spontaneous events, which indicate synchronous network activity, similar calcium signals...
Ionotropic glutamate receptors assemble as homo- or heterotetramers. One well-studied heteromeric complex is formed by the kainate receptor subunits GluK2 and GluK5. Retention motifs prevent trafficking of GluK5 homomers to plasma membrane, but coassembly with yields functional receptors. Additional control over GluK2/GluK5 assembly seems be exerted aminoterminal domains, which preferentially into heterodimers isolated domains. However,the stoichiometry full-length has yet determined, case...
The dynamics of peptide α-helices have been studied extensively for many years, and the kinetic mechanism helix–coil has discussed controversially. Recent experimental results suggested that equilibrium are governed by movement helix/coil boundary along chain, which leads to slower unfolding kinetics in helix center compared with ends position-independent formation kinetics. We tested this diffusion model helical peptides different lengths triplet-triplet energy transfer measurements data...
NMDA receptors are important players for neuronal differentiation. We previously reported that antagonizing with APV blocked the growth-promoting effects evoked by overexpression of specific calcium-permeable or flip-spliced AMPA receptor subunits and type I transmembrane regulatory proteins which both exclusively modify apical dendritic length branching cortical pyramidal neurons. These findings led us to characterize role GluN2B GluN2A dendritogenesis using organotypic cultures rat visual...