A5032809746- Lysosomal Storage Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Biochemical and Molecular Research
- Lipid Membrane Structure and Behavior
- Autophagy in Disease and Therapy
- Fungal and yeast genetics research
- Plant Reproductive Biology
- Hydrocarbon exploration and reservoir analysis
- Protein Structure and Dynamics
- Cardiac electrophysiology and arrhythmias
- Advanced MRI Techniques and Applications
- Cholesterol and Lipid Metabolism
- Advanced Fluorescence Microscopy Techniques
- Inflammasome and immune disorders
- Systemic Lupus Erythematosus Research
- Adenosine and Purinergic Signaling
- Calcium signaling and nucleotide metabolism
- Lipid metabolism and biosynthesis
- X-ray Spectroscopy and Fluorescence Analysis
- Microbial Metabolic Engineering and Bioproduction
- Atherosclerosis and Cardiovascular Diseases
- Cellular transport and secretion
- Advanced X-ray Imaging Techniques
University of Southern Denmark
2019-2024
The membrane protein Niemann-Pick type C1 (NPC1, named NCR1 in yeast) is central to sterol homeostasis eukaryotes.
Abstract Metabolic oscillations are a common phenomenon in cell biology. They based on non-linear coupling of biochemical reactions and can show rich dynamic behavior including sustained damped oscillations, as found, for example, glycolysis yeast other eukaryotic cells. often studied by time-lapse imaging cellular autofluorescence the changing abundance NAD(P)H, but analysis such experimental data is challenging. Here, we that mode decomposition (DMD), numerical algorithm linear...
During starvation in the yeast Saccharomyces cerevisiae vacuolar vesicles fuse and lipid droplets (LDs) can become internalized into vacuole an autophagic process named lipophagy. There is a lack of tools to quantitatively assess starvation-induced fusion lipophagy intact cells with high resolution throughput. Here, we combine soft X-ray tomography (SXT) fluorescence microscopy use deep-learning computational approach visualize quantify these processes yeast. We focus on homologs mammalian...
In eukaryotes, integration of sterols into the vacuolar/lysosomal membrane is critically dependent on Niemann-Pick type C (NPC) system. The system consists an integral protein, called NCR1 in yeast, and NPC2, a luminal soluble protein that transfers to N-terminal domain (NTD) before integration. Both proteins have been implicated sterol homeostasis yeast humans. Here, we investigate lipid binding NCR1/NPC2 transport determine crystal structures NTD. NTD binds both ergosterol cholesterol,...
Abstract Lipophagy is a form of autophagy by which lipid droplets (LDs) become digested to provide nutrients as cellular response starvation. often studied in yeast, Saccharomyces cerevisiae , LDs internalized into the vacuole. There lack tools quantitatively assess lipophagy intact cells with high resolution and throughput. Here, we combine soft X-ray tomography (SXT) fluorescence microscopy use deep learning computational approach visualize quantify yeast. We focus on yeast homologs...
Accumulation of cholesterol in the intima vessel walls is a hallmark developing atherosclerosis.An early event this process digestion oxidized and aggregated low-density lipoprotein (LDL) particles by macrophages (MΦs).In scavengerreceptor mediated process, MΦs attempt to engulf LDL triggering secretion hydrolytic enzymes from lysosomes, which turn hydrolyzes cholesteryl esters (CEs) residing (Fig. 1) [1].The massive generation non-esterified has two consequences; first, become heavily...
Abstract In eukaryotes, integration of sterols into the vacuolar/lysosomal membrane is critically dependent on Niemann-Pick type C (NPC) system. The system consists an integral protein, called NCR1 in yeast, and NPC2, a luminal soluble protein that transfers to N-terminal domain (NTD) before integration. Both proteins have been implicated sterol homeostasis yeast humans. Here, we investigate lipid binding NCR1/NPC2 transport determine crystal structures sterol-binding NTD. NTD binds both...
Soft X-ray tomography (SXT) enables native-contrast three-dimensional (3D) imaging of fully hydrated, cryogenically preserved biological samples, revealing ultrastructural details without the need for staining, embedding, or sectioning. Traditionally available only at synchrotron facilities, recent advances in laser-driven plasma sources have led to development compact soft microscopes, such as SXT-100. The SXT-100 achieves resolutions down 54 nm full-pitch, with tomograms acquired 30...
Abstract Polyene macrolides are antifungal substances, which interact with cells in a sterol-dependent manner. While being widely used, their mode of action is poorly understood. Here, we employ ultraviolet-sensitive (UV) microscopy to show that the polyene natamycin binds yeast plasma membrane (PM) and causes permeation propidium iodide into cells. Right before permeability becomes compromised, observed clustering PM was independent protein domains. Aggregation paralleled by cell...