A5064881493- PARP inhibition in cancer therapy
- Calcium signaling and nucleotide metabolism
- Sirtuins and Resveratrol in Medicine
- Autophagy in Disease and Therapy
- DNA Repair Mechanisms
- Chemical Synthesis and Analysis
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Blood disorders and treatments
- Heavy Metal Exposure and Toxicity
- Cell death mechanisms and regulation
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Toxin Mechanisms and Immunotoxins
- Protein Tyrosine Phosphatases
- Cardiovascular Issues in Pregnancy
- Clinical practice guidelines implementation
- RNA and protein synthesis mechanisms
- Inflammasome and immune disorders
- Endoplasmic Reticulum Stress and Disease
- Salivary Gland Disorders and Functions
- Click Chemistry and Applications
- Insect Resistance and Genetics
- Plant Virus Research Studies
- Insect symbiosis and bacterial influences
CeMM Research Center for Molecular Medicine
2023-2024
Austrian Academy of Sciences
2023-2024
University of Zurich
2016-2023
Life Science Zurich
2016-2021
Modèles Insectes de l'Immunité Innée
2017
Saarland University
2014
University College London
1979-1984
University College Hospital
1979-1984
Whittington Hospital
1984
St Mary's Hospital
1979
Mosquitoes genetically engineered to be resistant Plasmodium parasites represent a promising novel approach in the fight against malaria. The insect immune system itself is source of anti-parasitic genes potentially exploitable for transgenic designs. Anopheles gambiae thioester containing protein 1 (TEP1) potent protein. TEP1 secreted and circulates mosquito hemolymph, where its activated cleaved form binds eliminates malaria parasites. Here we investigated whether can used create...
The clostridium-like ecto-ADP-ribosyltransferase ARTC1 is expressed in a highly restricted manner skeletal muscle and heart tissue. Although well studied, the identification of targets vivo subsequent characterization ARTC1-regulated cellular processes on proteome level have been challenging only few ARTC1-ADP-ribosylated are known. Applying our recently developed mass spectrometry-based workflow to C2C12 myotubes tissues from wild-type mice, we identify hundreds proteins whose modifications...
In addition to its role as an electron transporter, mitochondrial nicotinamide adenine dinucleotide (NAD+) is important co-factor for enzymatic reactions, including ADP-ribosylation. Although mitochondria harbor the most intra-cellular NAD+, ADP-ribosylation remains poorly understood. Here we provide evidence ADP-ribosylation, which was identified using various methodologies immunofluorescence, western blot, and mass spectrometry. We show that reversibly increases in response respiratory...
Dysregulation of pathogen-recognition pathways the innate immune system is associated with multiple autoimmune disorders. Due to intricacies molecular network involved, identification pathway- and disease-specific therapeutics has been challenging. Using a phenotypic assay monitoring degradation adapter TASL, we identify feeblin, chemical entity which inhibits nucleic acid-sensing TLR7/8 pathway activating IRF5 by disrupting SLC15A4-TASL module. A high-resolution cryo-EM structure feeblin...
Though the effect of recently identified mitochondrial NAD+ transporter SLC25A51 on glucose metabolism has been described, its contribution to other NAD+-dependent processes throughout cell such as ADP-ribosylation remains elusive. Here, we report that absence leads increased concentration not only in cytoplasm and but also nucleus. The increase is associated with upregulation salvage pathway, implying an accumulation constitutively synthesized This results PARP1-mediated nuclear...
The labial biopsies from 13 patients with secondary Sjögren's syndrome (SS) and four disease controls were examined a panel of monoclonal antibodies to human leucocyte antigens. Large numbers T cells found in most the biopsies. In seven SS helper/inducer subset was be predominant. Antibody HLA class I antigens consistently stained leucocytes, but other cell types more variably. Although staining antibody II antigen often weak, approximately as many this an antileucocyte antibody, implying...
Solute carrier (SLC) transporters form a protein superfamily that enables transmembrane transport of diverse substrates including nutrients, ions and drugs. There are about 450 different SLCs, residing in variety subcellular membranes. Loss-of-function an unusually high proportion SLC is genetically associated with plethora human diseases, making SLCs rapidly emerging but challenging drug target class. Knowledge their environment may elucidate the molecular basis for functional integration...
Abstract Mice deficient for ADP-ribosyltransferase diphteria toxin–like 1 (ARTD1) are protected against microbially induced inflammation. To address the contribution of ARTD1 to inflammation specifically in myeloid cells, we generated an Artd1ΔMyel mouse strain with conditional deficiency lineages and examined three disease models. We found that ARTD1, but not its enzymatic activity, enhanced transcriptional activation distinct LPS-induced genes included IL-12, TNF-α, IL-6 primary bone...
ADP-ribosylation is involved in a variety of biological processes, many which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on cycle faces problem that synchronization with chemical agents or by serum starvation subsequent growth factor addition already activates itself. Here, we investigated functional contribution ARTD1 re-entry G1/S progression using T24 urinary bladder carcinoma cells, synchronously re-enter after splitting without...
In 48 patients undergoing renal biopsy there was a strong correlation (chi 2 11.45 (P less than 0.01)) between the demonstration of circulating and deposited immune complexes. Serial studies complex levels have shown fluctuations which only sometimes appear to coincide with clinical changes in individual patients.
While protein ADP-ribosylation was reported to regulate differentiation and dedifferentiation, it has so far not been studied during transdifferentiation. Here, we found that MyoD-induced transdifferentiation of fibroblasts myoblasts promotes the expression ADP-ribosyltransferase ARTD1. Comprehensive analysis genome architecture by Hi-C RNA-seq indicated ARTD1 locally contributed A/B compartmentalization coregulated a subset MyoD target genes were however sufficient alter Surprisingly,...
Non-essential metals are extremely toxic to living organisms, posing significant health risks, particularly in developing nations where they a major contributor illness and death. Although their toxicity is widely acknowledged, the mechanisms by which regulated within human cells remain incompletely understood. Specifically, role of membrane transporters mediating heavy metal not well comprehended. Our study demonstrates how specific can modulate cadmium, mercury, metalloid arsenic cells....
The advent of ligand-based receptor capture methodologies, allows the identification unknown candidates for orphan extracellular ligands. However, further target validation can be tedious, laborious and time-consuming. Here, we present a methodology that provides fast cost-efficient alternative candidate verification on living cells. In described ligand interest (e.g. transferrin, epidermal growth factor or insulin) was conjugated to linker (TriCEPS) carries biotin. To confirm...