A5016682467- Lipid Membrane Structure and Behavior
- Erythrocyte Function and Pathophysiology
- Cellular transport and secretion
- Blood properties and coagulation
- Sphingolipid Metabolism and Signaling
- Glycosylation and Glycoproteins Research
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- Neurobiology and Insect Physiology Research
- Adipose Tissue and Metabolism
- RNA Interference and Gene Delivery
- Lipid metabolism and biosynthesis
- Insect and Arachnid Ecology and Behavior
- Protein Structure and Dynamics
- Diabetes and associated disorders
- Liver Disease Diagnosis and Treatment
- Metabolism, Diabetes, and Cancer
- Physiological and biochemical adaptations
- Endoplasmic Reticulum Stress and Disease
- Nanopore and Nanochannel Transport Studies
- Cell death mechanisms and regulation
- Receptor Mechanisms and Signaling
- Acute Myeloid Leukemia Research
- Galectins and Cancer Biology
- Caveolin-1 and cellular processes
University Hospital Carl Gustav Carus
2018-2024
Paul Langerhans Institute Dresden
2015-2024
German Center for Diabetes Research
2014-2024
Heinrich Heine University Düsseldorf
2014-2024
Deutsches Diabetes-Zentrum e.V.
2014-2024
Technische Universität Dresden
2015-2024
Helmholtz Zentrum München
2019-2021
Max Planck Institute of Molecular Cell Biology and Genetics
2009-2013
University of Wrocław
2002-2013
Max Planck Society
2010-2012
Trained innate immunity fosters a sustained favorable response of myeloid cells to secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained acts via modulation hematopoietic stem and progenitor (HSPCs). Administration β-glucan (prototypical trained-immunity-inducing agonist) mice induced expansion progenitors the lineage, which was associated with elevated signaling by immune mediators, such as IL-1β granulocyte-macrophage colony-stimulating factor...
The physical basis for protein partitioning into lipid rafts remains an outstanding question in membrane biology that has previously been addressed only through indirect techniques involving differential solubilization by nonionic detergents. We have used giant plasma vesicles, a model system phase separates to include ordered enriching raft constituents, measure the of transmembrane linker activation T cells (LAT). LAT enrichment was dependent on palmitoylation at two juxtamembrane...
The human epidermal growth factor receptor (EGFR) is a key representative of tyrosine kinase receptors, ubiquitous actors in cell signaling, proliferation, differentiation, and migration. Although the well-studied, central issue remains: How does compositional diversity functional surrounding membrane modulate function? Reconstituting EGFR into proteoliposomes well-defined controlled lipid compositions represents minimal synthetic approach to systematically address this question. We show...
Biological membranes are compartmentalized for functional diversity by a variety of specific protein–protein, protein–lipid, and lipid–lipid interactions. A subset these the preferential interactions between sterols, sphingolipids, saturated aliphatic lipid tails responsible liquid–liquid domain coexistence in eukaryotic membranes, which give rise to dynamic, nanoscopic assemblies whose coalescence is regulated biochemical cues. Microscopic phase separation recently observed isolated plasma...
Significance Structural analysis of growth factor receptors in their membrane environment is key for understanding functions that are vital to the development and survival organisms. High structural flexibility posttranslational modifications full-length receptors, however, hinder at high resolution. Here, we used atomistic molecular dynamics simulations biochemical experiments with proteoliposomes elucidate role N -glycosylation regard properties human epidermal receptor (EGFR). We find...
Blood is arguably the most important bodily fluid and its analysis provides crucial health status information. A first routine measure to narrow down diagnosis in clinical practice differential blood count, determining frequency of all major cells. What lacking advance initial diagnostics an unbiased quick functional assessment that can generate specific hypotheses. To address this need, we introduce continuous, cell-by-cell morpho-rheological (MORE) diluted whole blood, without labeling,...
In biological processes, such as fission, fusion and trafficking, it has been shown that lipids of different shapes are sorted into regions with membrane curvatures. This lipid sorting hypothesized to be due the coupling between curvature lipid's spontaneous curvature, which is related molecular shape. On other hand, theoretical predictions simulations suggest preference lipids, shape alone, weaker than observed in processes. To distinguish these views, we have directly measured preferences...
Insulin receptor (IR) signaling plays a critical role in the regulation of metabolism and growth multicellular organisms. IRs are unique among tyrosine kinases that they exist exclusively as covalent (αβ)2 homodimers at cell surface. Transmembrane by IR can therefore not be based on ligand-induced dimerization such but must involve structural changes within existing dimer. In this study, using glycosylated full-length human reconstituted into lipid nanodiscs, we show single-particle electron...
Lateral compositional and physicochemical heterogeneity is a ubiquitous feature of cellular membranes on various length scales, from molecular assemblies to micrometric domains. Segregated lipid domains increased local order, referred as rafts, are believed be prominent features in eukaryotic plasma membranes; however, their exact nature (i.e. size, lifetime, composition, homogeneity) live cells remains difficult define. Here we present evidence that both synthetic natural assume wide range...
Galectins are unconventionally secreted lectins that participate in the formation of glycoprotein lattices perform a variety cell surface functions. also bind glycosphingolipid headgroups with as yet unclear implications for cellular physiology. We report specific interaction between galectin-9 and Forssman (FGL) is important polarizing Madin-Darby canine kidney epithelial cells. Galectin-9 knockdown leads to severe loss polarity can be rescued by addition recombinant protein. The FGL glycan...
The mechanisms underlying Golgi targeting and vesiculation are unknown, although the responsible phosphatidylinositol 4‐phosphate (PtdIns(4)P) ligand four‐phosphate‐adaptor protein (FAPP) modules have been defined. micelle‐bound structure of FAPP1 pleckstrin homology domain reveals how its prominent wedge independently tubulates membranes by leaflet penetration. Mutations compromising exposed hydrophobicity full‐length FAPP2 abolish lipid monolayer binding compression. trafficking process...
The conservation of fluidity is a theme common to all cell membranes. In this study, an analysis lipid packing was conducted via C-laurdan spectroscopy surface membranes prepared from representative species Bacteria and Eukarya. We found that despite their radical differences in composition (namely the presence absence membrane-rigidifying sterol) membrane order taxa converges on remarkably similar level. To understand how similarity constructed, we reconstituted with either bacterial or...
The interactions of the neurotransmitter dopamine, and its precursor l-dopa, with membrane lipids were investigated through a set molecular dynamic simulations all atom resolution. results obtained indicate that both dopamine l-dopa have pronounced association lipid head groups, predominantly mediated H-bonds. As result molecules are anchored to interfacial region membrane. strength this interaction is dependent on composition - presence phosphatidylserine leads an increase in interaction,...
The prevalence of diabetes mellitus and associated complications is steadily increasing. As a resource for studying systemic consequences chronic insulin insufficiency hyperglycemia, we established comprehensive biobank long-term diabetic INSC94Y transgenic pigs, model mutant INS gene-induced youth (MIDY), wild-type (WT) littermates.Female MIDY pigs (n = 4) were maintained with suboptimal treatment 2 years, together female WT littermates 5). Plasma insulin, C-peptide glucagon levels...
Shotgun lipidomics enables an extensive analysis of lipids from tissues and fluids. Each specimen requires appropriate extraction processing procedures to ensure good coverage reproducible quantification the lipidome. Adipose tissue (AT) has become a research focus with regard its involvement in obesity-related pathologies. However, AT lipidome is particularly challenging due predominance triacylglycerides, which elicit high ion suppression remaining lipid classes. We present new validated...