A5060638500- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Cellular Mechanics and Interactions
- Neural dynamics and brain function
- Photosynthetic Processes and Mechanisms
- Neuroscience and Neural Engineering
- Autophagy in Disease and Therapy
- Photoreceptor and optogenetics research
- Metabolomics and Mass Spectrometry Studies
- Axon Guidance and Neuronal Signaling
- Adipose Tissue and Metabolism
- Neurobiology and Insect Physiology Research
- Metabolism and Genetic Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Hereditary Neurological Disorders
- Multiple Sclerosis Research Studies
- Peripheral Neuropathies and Disorders
- Glioma Diagnosis and Treatment
- Planarian Biology and Electrostimulation
- Endoplasmic Reticulum Stress and Disease
- MicroRNA in disease regulation
- Molecular Biology Techniques and Applications
École Polytechnique Fédérale de Lausanne
2018-2024
ETH Zurich
2023-2024
Technical University of Munich
2011-2024
NCCR Chemical Biology - Visualisation and Control of Biological Processes Using Chemistry
2021
Czech Academy of Sciences, Institute of Physics
2019-2020
Munich Cluster for Systems Neurology
2018
German Center for Neurodegenerative Diseases
2018
Ludwig-Maximilians-Universität München
2015
Microtubule dynamics in neurons play critical roles physiology, injury and disease determine microtubule orientation, the cell biological correlate of neurite polarization. Several binding proteins, including end-binding protein 3 (EB3), specifically bind to growing plus tip microtubules. In past, fluorescently tagged proteins have revealed vitro non-mammalian model organisms. Here, we devise an imaging assay based on transgenic mice expressing yellow fluorescent protein-tagged EB3 study...
The cortical output layer 5 contains two excitatory cell types, slender- and thick-tufted neurons. In rat vibrissal cortex, slender-tufted neurons carry motion phase information during active whisking, but remain inactive after passive whisker touch. contrast, reliably increase spiking preferably By reconstructing the 3D patterns of intracortical axon projections from individual neurons, filled in vivo with biocytin, we were able to identify type-specific circuits that may encode Individual...
Developmental axon remodeling is characterized by the selective removal of branches from arbors. The mechanisms that underlie such branch loss are largely unknown. Additionally, how neuronal resources specifically assigned to arbors not understood. Here we show at developing mouse neuromuscular junction mediated branch-specific microtubule severing, which results in local disassembly cytoskeleton and axonal transport will subsequently dismantle. Accordingly, pharmacological stabilization...
Migration and pathfinding of neuronal growth cones during neurite extension is critically dependent on dynamic microtubules. In this study we sought to determine, which aspects microtubule polymerization relate cone morphology migratory characteristics. We conducted a multiscale quantitative microscopy analysis using automated tracking plus ends in migrating cultured murine dorsal root ganglion neurons. Notably, comprehensive failed identify any changes parameters that were specifically...
During mitochondrial fission, key molecular and cellular factors assemble on the outer membrane, where they coordinate to generate constriction. Constriction sites can eventually divide or reverse upon disassembly of machinery. However, a role for membrane tension in although speculated, has remained undefined. We capture dynamics constricting mitochondria mammalian cells using live-cell structured illumination microscopy (SIM). By analyzing diameters tubules that emerge from implementing...
Liver mitochondria play a central role in metabolic adaptations to changing nutritional states, yet their dynamic regulation upon anticipated changes nutrient availability has remained unaddressed. Here, we found that sensory food perception rapidly induced mitochondrial fragmentation the liver through protein kinase B/AKT (AKT)-dependent phosphorylation of serine 131 fission factor (MFFS131). This response was mediated by activation hypothalamic pro-opiomelanocortin (POMC)-expressing...
Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system, which resembles multiple sclerosis (MS). NMO differs from MS, however, in distribution and histology neuroinflammatory lesions shows a more aggressive clinical course. Moreover, majority patients carry immunoglobulin G autoantibodies against aquaporin-4 (AQP4), astrocytic water channel. Antibodies AQP4 can damage astrocytes by complement, but histopathology also demyelination, - importantly-axon injury, may...
Abstract Neural circuit development in the human cortex is considerably prolonged comparison to non-human primates, a trait that contributes remarkable cognitive capacity of modern humans. Here, we explore regulatory role non-coding RNAs, which dramatically expanded during brain evolution, synapse human-induced pluripotent stem-cell derived neurons. Inhibition human-specific microRNA, miR-1229-3p, results accelerated formation excitatory synapses and enhanced synaptic transmission....
Neuronal remodeling and myelination are two fundamental processes during neurodevelopment. How they influence each other remains largely unknown, even though their coordinated execution is critical for circuit function often disrupted in neuropsychiatric disorders. It unclear whether stabilizes axon branches or ongoing delays myelination. By modulating synaptic transmission, cytoskeletal dynamics, axonal transport mouse motor axons, we show that local onset node formation. Conversely, glial...
During mitotic entry of vertebrate cells, nuclear pore complexes (NPCs) are rapidly disintegrated. NPC disassembly is initiated by hyperphosphorylation linker nucleoporins (Nups), which leads to the dissociation FG repeat Nups and relaxation permeability barrier. However, less known about disintegration huge cytoplasmic rings, formed annular assemblies Y-complexes that dissociated from NPCs as intact units. Surprisingly, we observe Y-complex display slower kinetics compared with other during...
SUMMARY Mitochondrial fission is a highly regulated process which, when disrupted, can alter metabolism, proliferation and apoptosis 1–3 . The downstream effects have implications for many diseases, from neurodegeneration 4–6 to cardiovascular disease 7,8 cancer 9,10 Key components of the machinery been identified: constriction sites are initiated by endoplasmic reticulum (ER) 11 actin 12 before dynamin-related protein 1 (Drp1) 13 recruited outer mitochondrial membrane via adaptor proteins...
Despite a long history of anatomical mapping neuronal networks, we are only beginning to understand the detailed three-dimensional (3D) organization cortical micro-circuitry. This is in part due lack complete reconstructions individual neurons. Morphological studies either performed on incomplete cells vitro, or when vivo, necessary cellular resolution. We recently reconstructed vivo axonal and dendritic morphology two types L(ayer) 5 neurons from vibrissal cortex. The 3D profiles...
Despite a long history of anatomical mapping neuronal networks, we are only beginning to understand the detailed three-dimensional (3D) organization cortical micro-circuitry. This is in part due lack complete reconstructions individual neurons. Morphological studies either performed on incomplete cells vitro, or when vivo, necessary cellular resolution. We recently reconstructed vivo axonal and dendritic morphology two types L(ayer) 5 neurons from vibrissal cortex. The 3D profiles...
Abstract During mitochondrial fission, key molecular and cellular factors assemble on the outer membrane, where they coordinate to generate constriction. Constriction sites can eventually divide, or reverse upon disassembly of machinery. However, a role for membrane tension in although speculated, has remained undefined. We captured dynamics constricting mitochondria mammalian cells using live-cell structured illumination microscopy (SIM). By analyzing diameters tubules that emerge from...
Abstract BACKGROUND Diffuse Midline Gliomas (DMGs) present formidable challenges in neuro-oncology, prompting the exploration of innovative therapeutic strategies. Repurposing approved drugs, particularly those exhibiting multifaceted effects, holds promise for addressing these efficiently. In this study, we investigate potential trifluoperazine (TFP), an antipsychotic medication, with a specific focus on its mitochondrial-targeted actions DMGs. METHODS TFP, phenothiazine derivative,...
ABSTRACT The mechanisms of mitochondrial homeostasis in neurons—‘mitostasis’—are enigmatic and disease-prone, given a neuron’s large synaptic pool mitochondria. To better understand mitostasis mature mouse motor axons, we used ex vivo optical pulse-chase measurements volume flux identified reiterative degradation system near presynaptic terminals distal paranodes, which accounts for 75% turnover synapses. This filter captures dysfunctional mitochondria from the retrograde stream redirects...
Many molecular factors required for mitochondrial division have been identified; however, how they combine to physically trigger remains unknown. Here, we report that constriction by the machinery does not ensure mitochondria will divide. Instead, potential sites accumulate components and can constrict before either dividing, or relaxing back an unconstricted state. Using time-lapse structured illumination microscopy (SIM), find with higher local curvatures – reflecting increased membrane...