A5041830488- Advanced Fluorescence Microscopy Techniques
- Cell Image Analysis Techniques
- Advanced Biosensing Techniques and Applications
- Protein Kinase Regulation and GTPase Signaling
- Advanced biosensing and bioanalysis techniques
- 3D Printing in Biomedical Research
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- 14-3-3 protein interactions
- Neuroscience and Neuropharmacology Research
- Protein Structure and Dynamics
- DNA and Nucleic Acid Chemistry
- Single-cell and spatial transcriptomics
- Melanoma and MAPK Pathways
- Protein Degradation and Inhibitors
- Autophagy in Disease and Therapy
- Liver physiology and pathology
- Animal testing and alternatives
- RNA modifications and cancer
- Oxidative Organic Chemistry Reactions
- Ion channel regulation and function
- Mesoporous Materials and Catalysis
- Molecular Junctions and Nanostructures
- Galectins and Cancer Biology
TU Dortmund University
2023-2024
Max Planck Institute of Molecular Physiology
2022-2024
Heinrich Heine University Düsseldorf
2014-2022
Düsseldorf University Hospital
2022
Clemson University
2016-2018
Isfahan University of Technology
2014
Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro vivo. However, generalized protocols FRET standards ensure the reproducibility accuracy measurements efficiencies are currently lacking. Here we report results a comparative blind study which 20 labs determined (E) several dye-labeled DNA duplexes. Using unified, straightforward method, obtained with s.d. between ±0.02 ±0.05. We...
Targeted proteasomal and autophagic protein degradation, often employing bifunctional modalities, is a new paradigm for modulation of function. In an attempt to explore degradation by means autophagy we combine arylidene-indolinones reported bind the autophagy-related LC3B-protein ligands PDEδ lipoprotein chaperone, BRD2/3/4-bromodomain containing proteins BTK- BLK kinases. Unexpectedly, resulting degraders do not induce macroautophagy, but instead direct their targets ubiquitin-proteasome...
Abstract Previous studies of the N-terminal PDZ tandem from PSD-95 produced divergent models and failed to identify interdomain contacts stabilizing structure. We used ensemble single-molecule FRET along with replica-exchange molecular dynamics fully characterize energy landscape. Simulations experiments identified two conformations: an open-like conformation a small contact interface stabilized by salt bridges, closed-like larger surface-exposed hydrophobic residues. Both interfaces were...
Screening for small-molecule modulators of disease-relevant targets and phenotypes is the first step on way to new drugs. Large compound libraries have been synthesized by academia and, particularly, pharmaceutical companies meet need novel chemical entities that are as diverse possible. these revealed a portion small molecules inactive in more than 100 different assays was therefore termed "dark matter" (DCM). Deorphanization DCM promises yield very selective compounds they expected less...
RAS effectors specifically interact with GTP-bound proteins to link extracellular signals downstream signaling pathways. These interactions rely on two types of domains, called RAS-binding (RB) and association (RA) which share common structural characteristics. Although the molecular nature RAS-effector is well-studied for some proteins, most RA/RB-domain-containing remain largely uncharacterized. Here, we searched through human proteome databases, extracting 41 RA domains in 39 16 RB 14...
Mitochondria are cellular powerhouses and crucial for cell function. However, they vulnerable to internal external perturbagens that may impair mitochondrial function eventually lead death. In particular, small molecules impact function, therefore, their influence on homeostasis is at best assessed early in the characterization of biologically active drug discovery. We demonstrate unbiased morphological profiling by means painting assay (CPA) can detect stress coupled with induction an...
Targeted proteasomal and autophagic protein degradation, often employing bifunctional modalities, is a new paradigm for modulation of function. In an attempt to explore degradation by means autophagy we combined arylidene-indolinones reported bind the related LC3B-protein ligands PDE lipoprotein chaperone, BRD2/3/4-bromodomain containing proteins BTK- BLK kinases. Unexpectedly, resulting degraders do not induce macroautophagy, but instead direct their targets ubiquitin-proteasome system....
A protocol on how to perform high-precision interdye distance measurements using Förster resonance energy transfer (FRET) at the single-molecule level in multiparameter fluorescence detection (MFD) mode is presented here. MFD maximizes usage of all "dimensions" reduce photophysical and experimental artifacts allows for measurement with an accuracy up ~1 Å rigid biomolecules. This method was used identify three conformational states ligand-binding domain N-methyl-D-aspartate (NMDA) receptor...
This paper was originally published under standard Springer Nature copyright. As of the date this correction, Analysis is available online as an open-access with a CC-BY license. No other part has been changed.
Embryonic stem cell-expressed Ras (ERas) is an atypical constitutively active member of the family and controls distinct signaling pathways, which are critical, for instance, maintenance quiescent hepatic stellate cells (HSCs). Unlike classical paralogs, ERas has a unique N-terminal extension (Nex) with as yet unknown function. In this study, we employed affinity pull-down quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses identified 76 novel binding proteins...
Abstract Mitochondria are cellular powerhouses and crucial for cell function. However, these organelles vulnerable to internal external perturbagens that may impair mitochondrial function eventually lead death. In particular, small molecules impact cardio- or hepatotoxicity caused by numerous drugs links toxicity adverse effects. Therefore, the influence of on homeostasis is at best assessed early in characterization biologically active drug discovery. We demonstrate unbiased morphological...
A protocol on how to perform high-precision interdye distance measurements using Förster resonance energy transfer (FRET) at the single-molecule level in multiparameter fluorescence detection (MFD) mode is presented here. MFD maximizes usage of all "dimensions" reduce photophysical and experimental artifacts allows for measurement with an accuracy up ~1 Å rigid biomolecules. This method was used identify three conformational states ligand-binding domain N-methyl-D-aspartate (NMDA) receptor...
Abstract The identification of bioactive small molecules is at the heart chemical biology and medicinal research. screening for modulators disease-relevant targets phenotypes first step on way to new drugs. Therefore, large compound libraries have been synthesized employed by academia and, particularly, pharmaceutical companies meet need entities that are as diverse possible. Extensive these revealed a portion inactive in more than 100 different assays was therefore termed ‘dark matter’...
Mitochondria are cellular powerhouses and crucial for cell function. However, these organelles vulnerable to internal external perturbagens that may impair mitochondrial function eventually lead death. In particular, small molecules impact cardio- or hepatotoxicity caused by numerous drugs links toxicity adverse effects. Therefore, the influence of on homeostasis is at best assessed early in characterization biologically active drug discovery. We demonstrate unbiased morphological profiling...