A5018743537- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- 3D Printing in Biomedical Research
- Neural dynamics and brain function
- Photochromic and Fluorescence Chemistry
- Neuroscience and Neuropharmacology Research
- Marine Invertebrate Physiology and Ecology
- Single-cell and spatial transcriptomics
- RNA regulation and disease
- Neurobiology and Insect Physiology Research
- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced biosensing and bioanalysis techniques
- Metabolomics and Mass Spectrometry Studies
- Cellular Mechanics and Interactions
- Planarian Biology and Electrostimulation
- Pluripotent Stem Cells Research
- Microbial Metabolic Engineering and Bioproduction
- thermodynamics and calorimetric analyses
- Fish biology, ecology, and behavior
- Nicotinic Acetylcholine Receptors Study
- Cellular transport and secretion
University of Zurich
2014-2024
University of California, Santa Barbara
2018-2024
Altos Labs
2023
Universität Innsbruck
2014-2019
Life Science Zurich
2016
Human brain organoids replicate much of the cellular diversity and developmental anatomy human brain. However, physiology neuronal circuits within remains under-explored. With high-density CMOS microelectrode arrays shank electrodes, we captured spontaneous extracellular activity from derived induced pluripotent stem cells. We inferred functional connectivity spike timing, revealing a large number weak connections skeleton significantly fewer strong connections. A benzodiazepine increased...
Abstract Understanding metabolic heterogeneity is the key to uncovering underlying mechanisms of metabolic-related diseases. Current imaging studies suffer from limitations including low resolution and specificity, model systems utilized often lack human relevance. Here, we present a single-cell platform enable direct lipid metabolism with high specificity in various human-derived 2D 3D culture systems. Through incorporation an azide-tagged infrared probe, selective detection newly...
Mutations in the MAPT gene that encodes tau lead to frontotemporal dementia (FTD) with pathology evident both cerebral neurons and glia. Human organoids (hCOs) from individuals harboring pathogenic mutations can reveal earliest downstream effects on molecular pathways within a developmental context, generating interacting We found hCOs carrying V337M R406W mutations, cholesterol biosynthesis pathway astrocytes was top upregulated set compared isogenic controls by single-cell RNA sequencing...
In the central nervous system of vertebrates, glutamate serves as primary excitatory neurotransmitter. However, in retina, released from photoreceptors causes hyperpolarization post-synaptic ON-bipolar cells through a glutamate-gated chloride current, which seems paradoxical. Our research reveals that this current is modulated by two transporters, EAAT5b and EAAT7. zebrafish these transporters are located at dendritic tips interact with all four types cone photoreceptors. The absence leads...
Significance The pharmacophore of a clinically important prodrug, cytarabine (ara-C), was directly modified with an azide group that had little or no impact on its potency mode action. This “clickable” anticancer drug mimic unexpectedly revealed the efficient incorporation ara-C into DNA associated resistance rather than sensitivity. Our results therefore challenge long-standing perception regarding cell-type selectivity nucleoside-based drugs. mediators resistance, replication foci, were...
Metabolic incorporation of bioorthogonal functional groups into cellular nucleic acids can be impeded by insufficient phosphorylation nucleosides. Previous studies found that 5azidomethyl-2'-deoxyuridine (AmdU) was incorporated the DNA HeLa cells expressing a low-fidelity thymidine kinase, but not wild-type cells. Here we report membrane-permeable phosphotriester derivatives AmdU exhibit enhanced and animals. monophosphate bearing either 5'-bispivaloyloxymethyl (POM),...
The myc protooncogene encodes the Myc transcription factor which is essential part of Myc-Max network controlling fundamental cellular processes. Deregulation leads to tumorigenesis and a hallmark many human cancers. We have recently identified homologs (myc1, myc2) max in early diploblastic cnidarian Hydra characterized myc1 detail. Here we show that myc2 transcriptionally activated interstitial stem cell system. Furthermore, contrast myc1, expression also detectable proliferating...
The c-Myc protein is a transcription factor with oncogenic potential controlling fundamental cellular processes. Homologs of the human c-myc protooncogene have been identified in early diploblastic cnidarian Hydra (myc1, myc2). ancestral Myc1 and Myc2 proteins display principal design biochemical properties their vertebrate derivatives, suggesting that important Myc functions arose very metazoan evolution. part network regulated by several upstream pathways implicated oncogenesis...
Purpose: Mutations in CACNA2D4, encoding the α2δ4 subunit of retinal voltage-gated calcium channels (Cav), cause a rare type dysfunction human, mainly affecting cone vision. Here, we investigate role CACNA2D4 targeting Cav, its influence on cone-mediated signal transmission, and cellular subcellular changes upon loss by exploiting advantages cone-dominant zebrafish as model system. Methods: We identified two paralogs (cacna2d4a cacna2d4b), analyzed their expression RNA situ hybridization...
Human brain organoids replicate much of the cellular diversity and developmental anatomy human brain. However, neurophysiology within remains relatively under-explored. With high-density CMOS microelectrode arrays shank electrodes, we probed broadband three-dimensional activity organoids. From spiking activity, estimated a directed functional connectivity graph neural network which showed large number weak connections enmeshed skeleton significantly fewer strong connections. Increasing...
Metabotropic glutamate receptors (mGluRs) are mainly known for regulating excitability of neurons. However, mGluR6 at the photoreceptor-ON bipolar cell synapse mediates sign inversion through glutamatergic inhibition. Although this is currently only confirmed function mGluR6, other functions have been suggested. Here we present Tg(mglur6b:EGFP)zh1, a new transgenic zebrafish line recapitulating endogenous expression one two mglur6 paralogs in zebrafish. Investigating transgene as well...
Abstract Human brain organoids replicate much of the cellular diversity and developmental anatomy human brain. However, physiological behavior neuronal circuits within remains relatively under-explored. With high-density CMOS microelectrode arrays (26,400 electrodes) shank electrodes (960 electrodes), we probed broadband three-dimensional extracellular field recordings generated by spontaneous activity organoids. These simultaneously captured local potentials (LFPs) single-unit extracted...
Ca 2+ -binding proteins play important roles in neuronal function by transducing signals and thereby regulating crucial processes like synaptic signaling development, growth survival.The protein (CaBP) subfamily is part of the vast EF-hand containing calmodulin superfamily.Eight genes encoding CaBPs have been identified zebrafish, many them are expressed specific subpopulations retinal neurons during development.Among them, cabp2a cabp5b shown to be inner nuclear layer (INL).Here, we...
Understanding how human embryos develop their shape is a fundamental question in physics of life with strong medical implications. However, it challenging to study the dynamics organ formation humans. Animals differ from humans key aspects, and particular development nervous system. Conventional organoids are quantitatively unreproducible exhibit highly variable morphology. Here we present morphologically reproducible scalable approach for studying organogenesis dish, which compatible live...
Abstract In the central nervous system of vertebrates, glutamate serves as primary excitatory neurotransmitter. However, in retina, released from photoreceptors causes hyperpolarization postsynaptic ON-bipolar cells through a glutamate-gated chloride current, which seems paradoxical. Our research reveals that this current is modulated by two transporters, EAAT5b and EAAT7. These transporters are located at dendritic tips interact with all four types cone photoreceptors. The absence these...
Metabotropic glutamate receptors (mGluRs) are mainly known for regulating excitability of neurons. However, mGluR6 at the photoreceptor-ON bipolar cell synapse mediates sign inversion through glutamatergic inhibition. Although this is currently only confirmed function mGluR6, other functions have been suggested. Here we present Tg(mglur6b:EGFP)zh1, a new transgenic zebrafish line recapitulating endogenous expression one two mglur6 paralogs in zebrafish. Investigating transgene as well...