A5031011102- Cell Image Analysis Techniques
- Microtubule and mitosis dynamics
- Nuclear Structure and Function
- Image Processing Techniques and Applications
- Genomics and Chromatin Dynamics
- Advanced Fluorescence Microscopy Techniques
- AI in cancer detection
- RNA Research and Splicing
- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Cancer-related Molecular Pathways
- Genetics and Neurodevelopmental Disorders
- Glycogen Storage Diseases and Myoclonus
- Gene expression and cancer classification
- Kruppel-like factors research
- Autophagy in Disease and Therapy
- Lysosomal Storage Disorders Research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Metabolism, Diabetes, and Cancer
- Circular RNAs in diseases
- Advanced Electron Microscopy Techniques and Applications
RWTH Aachen University
2019-2025
Friedrich Miescher Laboratory
2014-2020
Max Planck Society
2014-2020
Universität Ulm
2013
Centre for Biomedical Network Research on Rare Diseases
2008-2011
Instituto de Biomedicina de Valencia
2008-2011
Centro de Investigación Biomédica en Red
2010-2011
In this work we present evidence that A769662, a novel activator of AMP‐activated protein kinase (AMPK), is able to inhibit the function 26S proteasome by an AMPK‐independent mechanism. Contrary mechanism action most inhibitors, A769662 does not affect proteolytic activities 20S core subunit, defining in way inhibition activity. Inhibition activity reversible and leads arrest cell cycle progression. These side effects new AMPK should be taken into account when compound used as alternative kinase.
Abstract During mitosis, chromosomes condense and decondense to segregate faithfully undamaged. The exact molecular mechanisms are not well understood. We identify the DEAD-box helicase eIF4A1/2 as a critical factor in this process. In cell-free condensation assay is crucial for process, relying on its RNA-binding ability but ATPase activity. Reducing levels cells consistently slows down chromatin decondensation during nuclear reformation. Conversely, increasing concentration mitotic...
Lafora progressive myoclonus epilepsy is a fatal neurodegenerative disorder caused by defects in the function of at least two proteins: laforin, dual-specificity protein phosphatase, and malin, an E3-ubiquitin ligase. In this study, we report that functional laforin-malin complex promotes ubiquitination AMP-activated kinase (AMPK), serine/threonine acts as sensor cellular energy status. This reaction occurs when any three AMPK subunits (alpha, beta, gamma) are expressed individually cell, it...
Abstract Myeloproliferative neoplasms (MPNs) encompass a diverse group of hematologic disorders driven by mutations in JAK2, CALR, or MPL. The prevailing working model explaining how these driver induce different disease phenotypes is based on the decisive influence cellular microenvironment and acquisition additional mutations. Here, we report increased levels chromatin segregation errors hematopoietic cells stably expressing CALRdel52 JAK2V617F Our investigations employing murine 32D MPL...
Mitosis is the process by which eukaryotic cells divide to produce two similar daughter with identical genetic material. Research into of mitosis therefore critical importance both for basic understanding cell biology and clinical approach manifold pathologies resulting from its malfunctioning, including cancer. In this paper, we propose an study mitotic progression automatically using deep learning. We used neural networks predict different stages. extracted video sequences undergoing...
The metazoan nucleus breaks down and reassembles during each cell division. Upon mitotic exit, the successful reestablishment of an interphase requires coordinated reorganization chromatin formation a functional nuclear envelope. Here we report that histone demethylase LSD1 plays crucial role in assembly at end mitosis. Downregulation cells extends telophase impairs pore complex assembly. In vitro, activity is required for recruitment MEL28/ELYS envelope precursor vesicles to chromatin,...
The eukaryotic nucleus remodels extensively during mitosis. Upon mitotic entry, the nuclear envelope breaks down and chromosomes condense into rod-shaped bodies, which are captured by spindle apparatus segregated anaphase. Through telophase, decondense reassembles, leading to a functional interphase nucleus. While molecular processes occurring in early mitosis intensively investigated, our knowledge about mechanisms of reassembly is rather limited. Using cell free cellular assays, we...
Live-cell imaging has become state of the art to accurately identify nature mitotic and cell cycle defects. Low- high-throughput microscopy setups have yield huge data amounts cells recorded in different experimental pathological conditions. Tailored semi-automated automated image analysis approaches allow high-content screening sets, saving time avoiding bias. However, they were mostly designed for very specific setups, which restricts their flexibility usability. The general need dedicated...
Abstract The mitotic spindle, essential for segregating the sister chromatids into two evolving daughter cells, is composed of highly dynamic cytoskeletal filaments, microtubules. dynamics microtubules are regulated by numerous microtubule associated proteins. We identify here Developmentally GTP binding protein 1 (DRG1) as a with diverse microtubule-associated functions. In vitro , DRG1 can diffuse on microtubules, promote their polymerization, drive formation bundles, and stabilize HeLa...
RecQ-like helicase 4 (RECQL4) is mutated in patients suffering from the Rothmund–Thomson syndrome, a genetic disease characterized by premature aging, skeletal malformations, and high cancer susceptibility. Known roles of RECQL4 DNA replication repair provide possible explanation chromosome instability observed patient cells. Here, we demonstrate that microtubule-associated protein (MAP) localizing to mitotic spindle. depletion M-phase–arrested frog egg extracts does not affect spindle...
During mitotic exit, thousands of nuclear pore complexes (NPCs) assemble concomitant with the envelope to build a transport-competent nucleus. Here, we show that Nup50 plays crucial role in NPC assembly independent its well-established function transport. RNAi-mediated downregulation cells or immunodepletion protein Xenopus egg extracts interferes assembly. We define conserved central region 46 residues is for Nup153 and MEL28/ELYS binding, interaction. Surprisingly, neither interaction nor...
Cell division, or mitosis, guarantees the accurate inheritance of genomic information kept in cell nucleus. Malfunctions this process cause a threat to health and life organism, including cancer other manifold diseases. It is therefore crucial study detail cell-cycle general mitosis particular. Consequently, large number manual semi-automated time-lapse microscopy image analyses have been carried out recent years. In paper, we propose method for automatic detection stages using recurrent...
Abstract Background Malin is an E3-ubiquitin ligase that mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms functional complex with laforin, glucan phosphatase facilitates targeting corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage malin. Results After extensive search for orthologs, we found present all vertebrate species and cephalochordate, contrast broader...
We introduce a fluorescent reporter for monitoring protein-protein interactions in living cells. The method is based on the Split-Ubiquitin and uses ratio of two auto-fluorescent proteins as signal interaction (SPLIFF). mating haploid yeast cells initiates analysis are followed online by two-channel time-lapse microscopy diploid during their first cell cycle. Using this approach we could with high spatio-temporal resolution visualize differences between microtubule binding protein Stu2p its...
Abstract Lack of high-quality antibodies against transmembrane proteins is a widely recognized hindrance in biomedical and cell biological research. Here we present robust pipeline for the generation polyclonal employing full-length membrane as immunogens to overcome this “antibody bottleneck”. We express fused MISTIC fragment that enhances expression eukaryotic E. coli. Purified are used immunogen rabbit injection standard immunizing protocols. The raised endoplasmic reticulum nuclear...
Platelets are key regulators of haemostasis, making platelet dysfunction a major driver thrombosis. Numerous processes that determine function influenced by microRNAs (miRs). MiR-26b is one the highest-expressed miRs in healthy platelets, and its expression platelets changed diseased state. However, exact effect this miR on has not been studied yet. In study, we made use whole-body knockout miR-26b ApoE-deficient mice order to impact function, thrombus formation signalling both ex vivo vivo....
ABSTRACT Cell division, or mitosis, guarantees the accurate inheritance of genomic information kept in cell nucleus. Malfunctions this process cause a threat to health and life organism, including cancer other manifold diseases. It is therefore crucial study detail cell-cycle general mitosis particular. Consequently, large number manual semi-automated time-lapse microscopy image analyses have been carried out recent years. In paper, we propose method for automatic detection stages using...