A5084994331- Ion channel regulation and function
- Pain Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Cardiac electrophysiology and arrhythmias
- COVID-19 Clinical Research Studies
- Nicotinic Acetylcholine Receptors Study
- Gut microbiota and health
- COVID-19 diagnosis using AI
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Advanced Proteomics Techniques and Applications
- Ion Channels and Receptors
- Pain Management and Placebo Effect
- Metabolomics and Mass Spectrometry Studies
- Neurobiology and Insect Physiology Research
- SARS-CoV-2 and COVID-19 Research
- Exercise and Physiological Responses
- Photoreceptor and optogenetics research
- Neuroscience and Neural Engineering
- Erythrocyte Function and Pathophysiology
- Heat shock proteins research
- Stress Responses and Cortisol
- Muscle metabolism and nutrition
- Machine Learning in Healthcare
- Vaccine Coverage and Hesitancy
University of Vienna
2021-2025
Max Planck Institute of Experimental Medicine
2007-2022
Nephrologisches Zentrum Goettingen
2015
Max Planck Society
2006-2014
University of California, San Diego
2009-2013
Universidad de Oviedo
1998-2008
Comprehensive, reproducible and precise analysis of large sample cohorts is one the key objectives quantitative proteomics. Here, we present an implementation data-independent acquisition using its parallel nature that surpasses limitation serial MS2 data-dependent on a quadrupole ultra-high field Orbitrap mass spectrometer. In deep single shot acquisition, identified quantified 6,383 proteins in human cell lines 2-or-more peptides/protein over 7100 when including 717 were basis peptide...
The potassium channel ether à go-go has been directly linked to cellular proliferation and transformation, although its physiologic role(s) are as of yet unknown. specific blockade human Eag1 (hEag1) may not only allow the dissection role in distinct processes, but because implication hEag1 tumor biology, it also offer an opportunity for treatment cancer. However, members superfamily structurally very similar one another, notoriously difficult obtain blockers any given channel. Here, we...
Introduction Metaproteomics is a rapidly advancing field that offers unique insights into the taxonomic composition and functional activity of microbial communities, their effects on host physiology. Classically, data-dependent acquisition (DDA) mass spectrometry (MS) has been applied for peptide identification quantification in metaproteomics. However, DDA-MS exhibits well-known limitations terms depth, sensitivity, reproducibility. Consequently, methodological improvements are required to...
Selective strengthening of specific glutamatergic synapses in the mammalian hippocampus is critical for encoding new memories. This most commonly achieved by input-specific Hebbian-type plasticity involving glutamate-dependent coincident presynaptic and postsynaptic depolarization. Our results demonstrate a novel mechanism which nicotinic signaling, independently fast transmission, increases synaptic strength hippocampus. Electrophysiological recordings from rat hippocampal neurons culture...
Piezo2 ion channels are critical determinants of the sense light touch in vertebrates. Yet, their regulation is only incompletely understood. We recently identified myotubularin related protein-2 (Mtmr2), a phosphoinositide (PI) phosphatase, native interactome murine dorsal root ganglia (DRG). Here, we demonstrate that Mtmr2 attenuates Piezo2-mediated rapidly adapting mechanically activated (RA-MA) currents. Interestingly, heterologous Piezo1 and other known MA current subtypes DRG appeared...
Mitochondrial dysfunction is associated with inflammatory bowel diseases (IBDs). To understand how microbial-metabolic circuits contribute to intestinal injury, we disrupt mitochondrial function in the epithelium by deleting chaperone, heat shock protein 60 (Hsp60
Modulation of the human ether‐à‐go‐go ‐related gene (HERG) K + channel was studied in two‐electrode voltage‐clamped Xenopus oocytes co‐expressing protein and thyrotropin‐releasing hormone (TRH) receptor. Addition TRH caused clear modifications HERG gating kinetics. These variations consisted an acceleration deactivation, as shown by a faster decay hyperpolarization‐induced tail currents, slower time course activation, measured using envelope tails protocol. The voltage dependence for...
Chronic pain is a complex disease with limited treatment options. Several profiling efforts have been employed the aim to dissect its molecular underpinnings. However, generated results are often inconsistent and nonoverlapping, which largely because of inherent technical constraints. Emerging data-independent acquisition (DIA)-mass spectrometry (MS) has potential provide unbiased, reproducible quantitative proteome maps - prerequisite for standardization among experiments. Here, we designed...
The aim of this study was to analyze whether the coronavirus disease 2019 (COVID-19) vaccine reduces mortality in patients with moderate or severe COVID-19 requiring oxygen therapy. A retrospective cohort study, data from 148 hospitals both Spain (111 hospitals) and Argentina (37 hospitals), conducted. We evaluated hospitalized for older than 18 years requirements. Vaccine protection against death assessed through a multivariable logistic regression propensity score matching. also performed...
The lateral mobility of surface receptors can define the signaling properties a synapse and rapidly change synaptic function. Here we use single-particle tracking with Quantum Dots to follow nicotinic acetylcholine (nAChRs) on chick ciliary ganglion neurons in culture. We find that both heteropentameric α3-containing (α3*-nAChRs) homopentameric α7-containing (α7-nAChRs) access domains by diffusion. They have comparable mobilities display Brownian motion extrasynaptic space but are...
The transient receptor potential A1 (TRPA1) channel is essential for vertebrate pain. Even though TRPA1 activation by ligands has been studied extensively, the molecular machinery regulating only poorly understood. Using an unbiased proteomics-based approach we uncovered physical association of Annexin A2 (AnxA2) with native in mouse sensory neurons. AnxA2 enriched a subpopulation neurons and coexpressed TRPA1. Furthermore, observe increase membrane levels cultured from AnxA2-deficient mice....
The use of data‐independent acquisition (DIA) approaches for the reproducible and precise quantification complex protein samples has increased in last years. information arising from DIA analysis is stored digital maps (DIA maps) that can be interrogated a targeted way by using ad hoc or publically available peptide spectral libraries generated on same sample species as generation maps. restricted availability certain difficult‐to‐obtain human tissues (i.e., brain) together with caveats...
The ability of somatosensory neurons to perceive mechanical stimuli relies on specialized mechanotransducing proteins and their molecular environment. Only recently has the identity a major transducer forces in vertebrates been revealed by discovery Piezo2. Further work established its pivotal role for innocuous touch mice. Therefore, Piezo2 offers unique platform investigation mechanosensation. We performed mass spectrometry-based interactomics screen native mouse dorsal root ganglia (DRG)....
Abstract After surgery, acute pain is still managed insufficiently and may lead to short-term long-term complications including chronic postsurgical an increased prescription of opioids. Thus, identifying new targets specifically implicated in postoperative utmost importance develop effective nonaddictive analgesics. Here, we used integrated multimethod workflow reveal unprecedented insights into proteome dynamics dorsal root ganglia (DRG) mice after plantar incision (INC). Based on a...
Acute pain after surgery is common and often leads to chronic post-surgical pain, but neither treatment nor prevention currently sufficient. We hypothesised that specific protein networks (protein-protein interactions) are relevant for in humans mice.Standardised surgical incisions were performed male human volunteers mice. Quantitative qualitative sensory phenotyping combined with unbiased quantitative mass spectrometry-based proteomics network theory. The primary outcomes skin signature...
Voltage-gated ion channels are main players involved in fast synaptic events. However, only slow intracellular mechanisms have so far been described for controlling their localization as real-time visualization of endogenous voltage-gated at high temporal and spatial resolution has not achieved yet. Using a specific extracellular antibody quantum dots we reveal characterize lateral mobility faster mechanism to dynamically control the number ether-a-go-go (Eag)1 inside synapses. We visualize...
Local control of calcium concentration within neurons is critical for signaling and regulation synaptic communication in neural circuits. How local can be achieved the absence physical compartmentalization poorly understood. Challenging examples are provided by nicotinic acetylcholine receptors that contain α7 receptor subunits (α7-nAChRs). These highly permeable to concentrated on aspiny dendrites interneurons, which lack obvious compartments constraining diffusion. Using functional...
Abstract Sensitization of the transient receptor potential ion channel vanilloid 1 (TRPV1) is critically involved in inflammatory pain. To date, manifold signaling cascades have been shown to converge onto TRPV1 and enhance its sensitization. However, many them also play a role for nociceptive pain, which limits their utility as targets therapeutic intervention. Here, we show that vesicle transport through interaction with t-SNAREs homolog 1B (Vti1b) protein promotes sensitization upon...
ABSTRACT Metaproteomics uniquely characterizes host-microbiome interactions. However, most species detected by metagenomics remain hidden to metaproteomics due sensitivity limits. We present a novel ultra-sensitive metaproteomic solution (uMetaP) that, for the first time, reaches full-length 16S rRNA taxonomic depth and can simultaneously decipher functional features. Querying mouse gut microbiome, uMetaP achieved unprecedented performance in key metrics like protein groups (47925) alongside...
Surface diffusion of postsynaptic receptors shapes synaptic transmission. Presynaptic also influence transmission, but the relevance their mobility for function is unknown. Using single-particle tracking with quantum dots, we show that calcium-permeable α7-containing nicotinic acetylcholine (α7–nAChRs), capable promoting transmitter release, are mobile on presynaptic terminals constrained in space rat hippocampal neurons culture. Additional immobilization α7-nAChRs by antibody crosslinking...
To obtain a thorough understanding of chronic pain, large-scale molecular mapping the pain axis at protein level is necessary, but has not yet been achieved. We applied quantitative proteome profiling to build comprehensive compendium three regions neuraxis in mice: sciatic nerve (SN), dorsal root ganglia (DRG), and spinal cord (SC). Furthermore, extensive bioinformatics analysis enabled us reveal unique subsets which are specifically enriched peripheral nervous system (PNS) SC. The immense...