A5031926815- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Cell Image Analysis Techniques
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Signaling Pathways in Disease
- Pancreatic function and diabetes
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- Gene expression and cancer classification
- Long-Term Effects of COVID-19
- Intensive Care Unit Cognitive Disorders
- Chromosomal and Genetic Variations
- Particle physics theoretical and experimental studies
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Particle Detector Development and Performance
- Cutaneous lymphoproliferative disorders research
- CAR-T cell therapy research
- Natural Antidiabetic Agents Studies
- Genetics, Aging, and Longevity in Model Organisms
- Single-cell and spatial transcriptomics
- COVID-19 Impact on Reproduction
Friedrich Miescher Institute
2016-2021
SIB Swiss Institute of Bioinformatics
2016-2021
Incyte (United States)
2020
Bühler (Switzerland)
2019
University of Cambridge
2014-2015
University of Chicago
2013
N 6 -methyladenosine (m A) is the most abundant mRNA modification in eukaryotes, playing crucial roles multiple biological processes. m A catalyzed by activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor methyltransferase components Drosophila and mice. Like other this...
Transcription termination determines the ends of transcriptional units and thereby ensures integrity transcriptome faithful gene regulation. Studies in yeast human cells have identified exoribonuclease XRN2 as a key factor for protein-coding genes. Here we performed genome-wide investigation RNA polymerase II (Pol II) transcription XRN2-deficient Caenorhabditis elegans observed two distinct modes termination. Although subset genes requires XRN2, other appears both independent of, refractory...
TRIM71/LIN-41, a phylogenetically conserved regulator of development, controls stem cell fates. Mammalian TRIM71 exhibits both RNA-binding and protein ubiquitylation activities, but the functional contribution either activity relevant primary targets remain poorly understood. Here, we demonstrate that shapes transcriptome mouse embryonic cells (mESCs) predominantly through its activity. We reveal binds 3′ untranslated region (UTR) hairpin motifs it acts by target degradation. mutations...
Abstract To gain insight into the mechanistic link between translation termination and nonsense-mediated mRNA decay (NMD), we depleted ribosome recycling factor ABCE1 in human cells, resulting an upregulation of NMD-sensitive mRNAs. Suppression NMD on these mRNAs occurs prior to their SMG6-mediated endonucleolytic cleavage. depletion caused stalling at codons (TCs) increased occupancy 3′ UTRs, implying enhanced TC readthrough. knockdown indeed rate readthrough continuation different reading...
Acute respiratory distress syndrome (ARDS) is the main complication of coronavirus disease 2019 (COVID-19), requiring admission to intensive care unit (ICU). Despite extensive immune profiling COVID-19 patients, what extent COVID-19-associated ARDS differs from other causes remains unknown. To address this question, here, we build 3 cohorts patients categorized in COVID-19-ARDS+, COVID-19+ARDS+, and COVID-19+ARDS-, compare, by high-dimensional mass cytometry, their landscape. A cell...
Drosophila melanogaster has been widely used as a model of human Mendelian disease, but its value in modeling complex disease received little attention. Fly models would enable high-resolution mapping disease-modifying loci and the identification novel targets for therapeutic intervention. Here, we describe fly permanent neonatal diabetes mellitus explore complexity this model. The approach involves transgenic expression misfolded mutant preproinsulin, hINS(C96Y), which is cause diabetes....
ABSTRACT Brain metastasis (BrM) represents a devastating complication across various cancer types, posing as significant contributor to global morbidity and mortality. Hence, identifying robust biomarkers for early detection types with propensity BrMs their therapeutic targeting is highly timely critical. In this study, we leveraged single-cell RNA sequencing (scRNA-seq) data from six combined convolutional neural network (CNN)-based ScaiVision algorithm identify pan-cancer BrM signature...
XRN2 is a conserved 5'→3' exoribonuclease that complexes with proteins contain XRN2-binding domains (XTBDs). In Caenorhabditis elegans (C. elegans), the XTBD-protein PAXT-1 stabilizes to retain its activity. activity also promoted by 3'(2'),5'-bisphosphate nucleotidase 1 (BPNT1) through hydrolysis of an endogenous XRN inhibitor 3'-phosphoadenosine-5'-phosphate (PAP). Here, we find unbiased screening loss bpnt-1 function suppresses lethality caused paxt-1 deletion. This unexpected finding...
Group B Sox proteins are a highly conserved group of transcription factors that act extensively to coordinate nervous system development in higher metazoans while showing both co-expression and functional redundancy across broad taxa. In Drosophila melanogaster, the two Dichaete SoxNeuro show widespread common binding genome. While some instances compensation have been observed Drosophila, function extent its evolutionary conservation is not known. We used DamID-seq examine genome-wide...
ABSTRACT Adenine auxotrophy is a commonly used non-selective genetic marker in yeast research. It allows investigators to easily visualize and quantify various epigenetic events by simply reading out colony color. However, manual counting of large numbers colonies extremely time-consuming, difficult reproduce possibly inaccurate. Using cutting-edge neural networks, we have developed fully automated pipeline for segmentation classification, which speeds up white/red quantification 100-fold...
Small non-protein coding RNAs are involved in pathways that control the genome at level of chromatin. In Schizosaccharomyces pombe, small interfering (siRNAs) required for faithful propagation heterochromatin is found peri-centromeric repeats. contrast to repetitive DNA, protein-coding genes refractory siRNA-mediated formation, unless siRNAs expressed mutant cells. Here we report identification 20 novel alleles enable de novo formation a euchromatic gene by using trans-acting as triggers....
Abstract Background: Next generation sequencing (NGS) is a widely used technology in both basic research and clinical settings it will continue to have major impact on biomedical sciences. However, the use of incorrect normalization methods can lead systematic biases spurious results, making selection an appropriate strategy crucial often overlooked part NGS analysis. Results: We present introduction currently available for differential expression ChIP-seq applications, along with best...
SUMMARY Nonsense-mediated mRNA decay (NMD) is an essential post-transcriptional surveillance pathway in vertebrates that appears to be mechanistically linked with translation termination. To gain more insight into this connection, we interfered termination by depleting human cells of the ribosome recycling factor ABCE1, which resulted upregulation many but not all endogenous NMD-sensitive mRNAs. Notably, suppression NMD on these mRNAs occurs at a step prior their SMG6-mediated...
Abstract Introduction Over 24 million people have been infected globally with the novel coronavirus, SARS-CoV-2, more than 820,000 succumbing to resulting COVID-19 disease as of end August 2020. The molecular mechanisms underlying pathogenesis are not completely elucidated. Thus, we aim understand host response SARS-CoV-2 infection by comparing samples collected from two distinct compartments (infection site and blood), obtained subjects healthy controls. Methods We used publicly available...
The age-related mortality and morbidity risk of COVID-19 has been considered speculative without enough scientific evidence. This study aimed to collect more evidence on the association between patient age severe disease state and/or from SARS-CoV-2 infection. Genomic dataset along with metadata (3608 samples) retrieved GISAID different geographical regions were grouped into 10 groups (0-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100 years) as well high-risk or low-risk...
Summary Small RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At same time, their activity needs be well-controlled prevent silencing ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) in Caenorhabditis elegans germline protect genome integrity fertility. We find WAGO-1 WAGO-3 Argonaute (Ago) proteins are matured through processing unusually proline-rich N-termini. In...
Dominant negative mutations in the insulin gene are second most common cause of permanent neonatal diabetes. However, variation severity and penetrance diabetes, as other complex genetic diseases, cannot be accounted for by known disease mutations. In a novel approach to this problem, we have utilized tools available Drosophila model effects C96Y mutation, cysteine tyrosine mutation protein that can diabetes humans. This which disrupts disulfide bridge proinsulin molecule, has been shown...
Here we use Drosophila melanogaster to create a genetic model of human permanent neonatal diabetes mellitus and present experimental results describing dimensions this complexity. The approach involves the transgenic expression misfolded mutant preproinsulin, hINSC96Y, which is cause disease. When expressed in fly imaginal discs, hINSC96Y causes reduction adult structures, including eye, wing notum. Eye discs exhibit defects both structure arrangement ommatidia. In wing, leads ectopic veins...
Abstract Background Adenine auxotrophy is a commonly used non-selective genetic marker in yeast research. It allows investigators to easily visualize and quantify various epigenetic events by simply reading out colony color. However, manual counting of large numbers colonies extremely time-consuming, difficult reproduce possibly inaccurate. Results Using cutting-edge neural networks, we have developed fully automated pipeline for segmentation classification, which speeds up white/red...