A5052134873- Neuroscience and Neuropharmacology Research
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- Ubiquitin and proteasome pathways
- Memory and Neural Mechanisms
- Advanced Proteomics Techniques and Applications
- Multiple Myeloma Research and Treatments
- Skin Protection and Aging
- Antioxidant Activity and Oxidative Stress
- Genomics, phytochemicals, and oxidative stress
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- Genetic and Kidney Cyst Diseases
- Immune Cell Function and Interaction
- Neurobiology and Insect Physiology Research
- Phytochemicals and Antioxidant Activities
- Neurotransmitter Receptor Influence on Behavior
- Biomedical Research and Pathophysiology
- Mass Spectrometry Techniques and Applications
- Hedgehog Signaling Pathway Studies
- Cancer Research and Treatments
- Mitochondrial Function and Pathology
- Amino Acid Enzymes and Metabolism
- Neuropeptides and Animal Physiology
- Phosphodiesterase function and regulation
Institute of Cancer Research
2022-2024
Institute of Cancer Research
2023
University of Vienna
2016-2022
Cancer Research UK
2022
University of Salzburg
2020-2021
Medical University of Vienna
2012-2018
University of Graz
2018
CeMM Research Center for Molecular Medicine
2015-2016
Austrian Academy of Sciences
2015-2016
Small molecules that induce protein degradation hold the potential to overcome several limitations of currently available inhibitors. Monovalent or molecular glue degraders, in particular, enable benefits without disadvantages high weight and resulting challenge drug development are associated with bivalent like Proteolysis Targeting Chimeras. One key designing monovalent degraders is how build degrader activity─how can we convert an inhibitor into a degrader? If activity requires very...
Membrane proteins play key roles in several fundamental biological processes such as cell signalling, energy metabolism and transport. Despite the significance, these still remain an under-represented group proteomics datasets. Herein, a bottom-up approach to analyse enriched membrane fraction from Drosophila melanogaster heads using multidimensional liquid chromatography (LC) coupled with tandem-mass spectrometry (MS/MS) that relies on complete solubilisation digestion of proteins, is...
Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. isozymes have been consistently related to cell proliferation, but GLS2 remains poorly understood. is repressed many tumor cells better understanding its function tumorigenesis may further development new therapeutic approaches. We analyzed expression HCC, GBM neuroblastoma cells, as well monkey COS-7 cells....
Ultraviolet light is the dominant environmental oxidative skin stressor and a major aging factor. We studied which oxidized phospholipid (OxPL) mediators would be generated in primary human keratinocytes (KC) upon exposure to ultraviolet A (UVA) investigated contribution of OxPL UVA responses. Mass spectrometric analysis immediately or 24 h post UV stress revealed significant changes abundance 173 84 lipid species, respectively. identified known novel species including bioactive also...
Drebrin an actin-bundling key regulator of dendritic spine genesis and morphology, has been recently proposed as a hippocampal glutamatergic activity which is critical for memory formation maintenance. Here, we examined the effects genetic deletion drebrin on level complexes containing major brain receptors. To this end, homozygous heterozygous knockout mice generated in our laboratory related wild-type control animals were studied. Level protein dopamine receptor D1/dopamine D2,...
Abstract Small molecules inducing protein degradation are important pharmacological tools to interrogate complex biology and rapidly translating into clinical agents. However, fully realise the potential of these molecules, selectivity remains a limiting challenge. Herein, we addressed issue in design CRL4 CRBN recruiting PROteolysis TArgeting Chimeras (PROTACs). Thalidomide derivatives used generate PROTACs have well described intrinsic monovalent profiles by recruitment neo‐substrates,...
Large scale proteomic profiling of cell lines can reveal molecular signatures attributed to variable genotypes or induced perturbations, enabling proteogenomic associations and elucidation pharmacological mechanisms action. Although isobaric labeling has increased the throughput analysis, commonly used sample preparation workflows often require time-consuming steps costly consumables, limiting their suitability for large studies. Here, we present a simplified cost-effective one-pot reaction...
To address the limitation associated with degron based systems, we have developed iTAG, a synthetic tag on IMiDs/CELMoDs mechanism of action that improves and addresses limitations both PROTAC previous IMiDs/CeLMoDs tags. Using structural sequence analysis, systematically explored native chimeric containing domains (DCDs) evaluated their ability to induce degradation. We identified optimal iTAG(DCD23 60aa) elicits robust degradation targets across cell types subcellular localizations without...
Disrupted-in-schizophrenia 1 (DISC1) is a key protein involved in behavioral processes and various mental disorders, including schizophrenia major depression. A transgenic rat overexpressing non-mutant human DISC1, modeling aberrant proteostasis of the DISC1 protein, displays behavioral, biochemical anatomical deficits consistent with aspects changes dorsal striatum, an region critical development disorders. Herein, striatum 10 tgDISC1 wild type rats was used for synaptosomal preparations...
The molecular composition of synaptic signal transduction machineries shapes neurotransmission. repertoire receptors, transporters and channels (RTCs) comprises major signaling events in the brain. RTCs are conventionally studied by candidate immunohistochemistry biochemistry, which low throughput with resolution greatly affected available immunoreagents membrane interference. Therefore, a comprehensive resource brain is still lacking. In particular, studies on detergent-soluble synaptosomal...
Bardet-Biedl syndrome (BBS), a ciliopathy, is rare genetic condition characterised by retinal degeneration, obesity, kidney failure, and cognitive impairment. In spite of progress made in our general understanding BBS aetiology, the molecular cellular mechanisms underlying impairment remain elusive. Here, we report that loss proteins causes synaptic dysfunction principal neurons, providing possible explanation for phenotype observed patients. Using synaptosomal proteomics...
Dopamine (DA) is critically involved in different functions of the central nervous system (CNS) including control voluntary movement, affect, reward, sleep, and cognition. One key components DA neurotransmission reuptake by transporter (DAT), ensuring rapid clearance from synaptic cleft. Thus, lack DAT leads to persistent high extracellular levels. While there strong evidence for a role striatal dopaminergic activity learning memory processes, little known about contribution deficiency...
The Spanish slug, Arion vulgaris, is considered one of the hundred most invasive species in Central Europe. immense and very successful adaptation spreading A. vulgaris suggest that it developed highly effective mechanisms to deal with infections natural predators. Current transcriptomic proteomic studies on gastropods have been restricted mainly marine freshwater gastropods. No or study has carried out so far, current study, first database from adult specimen reported. To facilitate enable...
Fragile X mental retardation protein (FMRP) encoded by 1 (FMR1) gene is a RNA-binding regulator of mRNA translation, transport and stability with multiple targets responsible for proper synaptic function. Epigenetic silencing FMR1 expression leads to the development Syndrome (FXS) that characterized intellectual disability other behavioral problems including autism. In rat FXS model, lack FMRP caused deficit in hippocampal-dependent memory. However, hippocampal changes aging rats are not...
Corticosteroid and endocannabinoid actions converge on prefrontocortical circuits associated with neuropsychiatric illnesses. Corticosteroids can also modulate forebrain synapses by using effector systems. Here, we determined whether corticosteroids transmitter release directly in the frontal cortex and, doing so, they affect presynaptic CB1 cannabinoid receptor- (CB1R) mediated neuromodulation. By Western blotting of purified subcellular fractions rat cortex, found glucocorticoid receptors...
Abstract The swim bladder of a fish is vital organ that with gas gland cells in the wall enables key physiological functions including buoyancy regulation face different hydrostatic pressures. Specific produce and secrete acidic metabolites into blood order to reduce physical solubility gases transport capacity for regulating volume bladder. Transcriptomic analyses have provided evidence at RNA level but no specific studies protein been carried out so far. Herein, it was aim study show...
Zebrafish (Danio rerio) is a well-established model organism in developmental biology and disease modeling. In recent years, an increasing amount of studies used zebrafish to analyze the genetic changes underlying various neurological disorders. The brain plasma membrane proteome represents major subsets signaling proteins promising drug targets, but often understudied due traditional experimental difficulties including problems with solubility, detergent removal, or low abundance. Here, we...