A5091105015- Zebrafish Biomedical Research Applications
- Cellular transport and secretion
- Hepatitis C virus research
- RNA modifications and cancer
- RNA Research and Splicing
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Liver Disease Diagnosis and Treatment
- Neuroscience of respiration and sleep
- Neurogenesis and neuroplasticity mechanisms
- Spinal Cord Injury Research
- RNA regulation and disease
- Influenza Virus Research Studies
- Neurogenetic and Muscular Disorders Research
- MicroRNA in disease regulation
- Hepatitis B Virus Studies
- Hair Growth and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Skin and Cellular Biology Research
- Autophagy in Disease and Therapy
- Apelin-related biomedical research
- Liver physiology and pathology
- Osteoarthritis Treatment and Mechanisms
- Cellular Mechanics and Interactions
- Hearing, Cochlea, Tinnitus, Genetics
TU Dresden
2022-2024
University of Edinburgh
2019-2023
University Hospital Bonn
2009-2022
Discovery Centre
2019-2020
University of Bonn
2009-2019
Institutul Cantacuzino
2008
Synaptic vesicles are embedded in a complex filamentous network at the presynaptic terminal. Before fusion, linked to active zone (AZ) by short filaments (tethers). The identity of molecules that form and regulate tethers remains unknown, but Rab3-interacting molecule (RIM) is prominent candidate, given its central role AZ organization. In this paper, we analyzed architecture RIM1α knockout (KO) mice cryo-electron tomography. stark contrast previous work on dehydrated, chemically fixed...
Stable function of networks requires that synapses adapt their strength to levels neuronal activity, and failure do so results in cognitive disorders. How such homeostatic regulation may be implemented mammalian remains poorly understood. Here we show the phosphorylation status several positions active-zone (AZ) protein RIM1 are relevant for synaptic glutamate release. Position RIMS1045 is necessary sufficient expression silencing-induced plasticity kept phosphorylated by serine arginine...
Rab interacting molecules (RIMs) are multi-domain proteins that positively regulate the number of Ca2+ channels at presynaptic active zone (AZ). Several molecular mechanisms have been demonstrated for RIM-binding to components channel complex, key signaling element AZ. Here, we report an interaction C2B domain RIM2α and RIM3γ with C-terminus pore-forming α–subunit CaV1.3 (CaV1.3α1), which mediate stimulus-secretion coupling ribbon synapses cochlear inner hair cells (IHCs). Co-expressing...
Prolonged inflammation after spinal cord injury is detrimental to recovery. To find pharmacological modulators of the response, we designed a rapid drug screening paradigm in larval zebrafish followed by testing hit compounds mouse model. Methods: We used reduced il-1β linked green fluorescent protein (GFP) reporter gene expression as read-out for screen 1081 zebrafish. Hit drugs were tested moderate contusion model mice cytokine regulation, and improved tissue preservation locomotor...
Mechanisms that regulate the formation of membrane-less cellular organelles, such as neuronal RNA granules and stress granules, have gained increasing attention over past years. These consist a plethora RNA-binding proteins. Mutations in proteins been found neurodegenerative diseases amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD). By performing pulldown experiments subsequent mass spectrometry on mouse brain lysates, we discovered de-ubiquitylating enzyme OTU...
ABSTRACT Synapses are particularly vulnerable in many neurodegenerative diseases and often the first to degenerate, for example motor neuron disease spinal muscular atrophy (SMA). Compounds that can counteract synaptic destabilisation rare. Here, we describe an automated screening paradigm zebrafish small-molecule compounds stabilize neuromuscular synapse vivo. We make use of a mutant axonal C-type lectin chondrolectin (chodl), one main genes dysregulated SMA. In chodl−/− mutants, synapses...
Chondrolectin (Chodl) is needed for motor axon extension in zebrafish and dysregulated mouse models of spinal muscular atrophy (SMA). However, the mechanistic basis Chodl function not known. Here, we use Chodl-deficient mutants to show that absence leads anatomical functional defects neuromuscular synapse. In zebrafish, growth an identified beyond "en passant" synapse later branching from synaptic points are impaired, leading deficits. Mechanistically, motor-neuron-autonomous depends on its...
Key points A T258F mutation of the glycine receptor increases affinity to endogenous agonists, modifies single‐channel conductance and shapes response decay kinetics. Glycine receptors cerebellar granule cells play their functional role not continuously, but when cell layer starts receiving a high amount excitatory inputs. Despite relative scarcity, tonically active make significant impact on action potential generation inter‐neuronal crosstalk, modulate synaptic plasticity in neural...
During ontogeny, neural stem cells in the spinal cord cease production of neurons. Spinal injury re-initiates neurogenesis anamniotes (amphibians and fishes), but not mammals. It is unclear whether regenerative from progenitor simply depends on recapitulation developmental signals intracellular signal transduction or driven by mechanisms that are unique to regeneration. Using single cell RNAseq macrophages, as well type-specific manipulations, we provide evidence for a direct signalling axis...
ABSTRACT Zebrafish, in contrast to mammals, regenerate neurons after spinal cord injury, but little is known about the control mechanisms of this process. Here we show that microglia are main cell type express evolutionarily conserved signalling molecule sema4ab injury site. Deletion doubles number newly generated progenitor cells and injury. Using scRNAseq all lesion site types gene disruption, find supports microglial activation state promotes interactions with fibroblasts neural cells....
Stable function of networks in the brain requires that synapses adapt their strength to levels neuronal activity a durable manner and failures do so result cognitive disorders. How such persistent homeostatic regulation synaptic connections may be biologically implemented mammalian remains poorly understood. Here, we have employed optical recordings vesicle release from single synapses, super-resolution microscopy, phosphoproteomics reveal level transmitter is stored phosphorylation state...
Since the early 2000s, popularity of zebrafish in vivo drug screening has shown a substantial increase. The become an important tool covering wide range tissue-specific pathologies and diseases/disorders. Nowadays phenotype-based is favoured over target-based approaches, because it can identify active drugs/small molecules absence known target or suspected mechanism action. Phenotypic screens not only compounds with positive effect, but also off-target effect. Another advantage...
Introduction: Gba2 knockout mice accumulate the glycolipid glucosylceramide in different tissues, including liver. Glycolipids are a class of cellular membrane lipids that differ from regular phospholipids remarkable variation its head group structures. This suggests glycolipids serve specialized functions cell signaling, differentiation and recognition processes (van Meer et al. 2003). Different studies have suggested special role cycle proliferation. Our aim was to investigate liver...
Introduction: Gaucher disease, the most common inherited lysosomal storage disorder in humans, is caused by mutations gene encoding enzyme glucocerebrosidase (GBA1). The deficiency of GBA1 results accumulation glucosylceramide macrophage lysosome, which leads to liver and spleen enlargements, bone lesions, severe cases, impairment central nervous system function. Three types disease have been described: Type I marked absence neurological involvement shows generally a milder form; II III are...