A5058477479- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health and Medical Studies
- Medical and Health Sciences Research
- Advanced biosensing and bioanalysis techniques
- Reproductive biology and impacts on aquatic species
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Medical Practices and Rehabilitation
- Genomics and Chromatin Dynamics
- MicroRNA in disease regulation
- Biosensors and Analytical Detection
- Apelin-related biomedical research
- Criminal Law and Policy
- CRISPR and Genetic Engineering
- Nuclear Receptors and Signaling
- SARS-CoV-2 detection and testing
- Sex and Gender in Healthcare
- Zebrafish Biomedical Research Applications
- Economic and Social Issues
Research Institute of Molecular Pathology
2016-2025
Vienna Biocenter
2016-2024
Harvard University
2010-2017
Bielefeld University
2011-2016
University of Oxford
2006-2011
Broad Institute
2011
Heidelberg University
2006
DKFZ-ZMBH Alliance
2004
German Cancer Research Center
2004
The CRISPR/Cas9 system has been implemented in a variety of model organisms to mediate site-directed mutagenesis. A wide range mutation rates reported, but at limited number genomic target sites. To uncover the rules that govern effective Cas9-mediated mutagenesis zebrafish, we targeted over hundred loci for using streamlined and cloning-free method. We generated mutations 85% genes with varying across several orders magnitude, identified sequence composition influence increased by...
Long noncoding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in humans and the mouse have annotated lncRNAs expressed cell lines adult tissues, systematic analysis during vertebrate embryogenesis has been elusive. To identify with potential functions embryogenesis, we performed time-series RNA-seq experiments at eight stages early zebrafish development. We reconstructed 56,535 high-confidence...
It has been assumed that most, if not all, signals regulating early development have identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence overproduction of Toddler reduce the movement mesendodermal cells gastrulation. Local ubiquitous production promote cell movement, suggesting is neither an attractant nor repellent but acts globally as...
Large-scale genomics and computational approaches have identified thousands of putative long non-coding RNAs (lncRNAs). It has been controversial, however, as to what fraction these is truly non-coding. Here, we combine ribosome profiling with a machine-learning approach validate lncRNAs during zebrafish development in high throughput manner. We find that dozens proposed are protein-coding contaminants many profiles resemble the 5' leaders coding RNAs. Analysis data from embryonic stem cells...
Abstract Upstream open reading frames (uORFs) are ubiquitous repressive genetic elements in vertebrate mRNAs. While much is known about the regulation of individual genes by their uORFs, range uORF-mediated translational repression genomes largely unexplored. Moreover, it unclear whether effects uORFs conserved across species. To address these questions, we analyse transcript sequences and ribosome profiling data from human, mouse zebrafish. We find that depleted near coding (CDSes) have...
Cohesin is a highly conserved multisubunit complex that holds sister chromatids together in mitotic cells. At the metaphase to anaphase transition, proteolytic cleavage of alpha kleisin subunit (Rad21) by separase causes cohesin's dissociation from chromosomes and triggers sister-chromatid disjunction. To investigate function postmitotic cells, where it widely expressed, we have created fruit flies whose Rad21 can be cleaved TEV protease. Cleavage precocious separation massive chromosome...
The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to Pol C-terminal domain dismantles elongating from DNA vitro. We demonstrate that PCF11-mediated termination essential for vertebrate development. range genomic analyses, including mNET-seq, 3′ mRNA-seq, chromatin RNA-seq, ChIP-seq, reveals PCF11 enhances stimulates early genome-wide....
Bouncer keeps fertilization specific Fertilization needs to be highly efficient while remaining species-specific. However, despite decades of research, it is still unclear how these two requirements are met. Herberg et al. report the discovery Ly6/uPAR-type protein as a species-specific factor in zebrafish (see Perspective by Lehmann). localizes egg membrane and required for sperm entry. Remarkably, expression from another fish species (medaka) allowed cross-species fertilization. Science ,...
RT-qPCR-based diagnostic tests play important roles in combating virus-caused pandemics such as Covid-19. However, their dependence on sophisticated equipment and the associated costs often limits widespread use. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative nucleic acid detection method that overcomes these limitations. Here, we present a rapid, robust, sensitive RT-LAMP-based SARS-CoV-2 assay. Our 40-min procedure bypasses RNA isolation...
Abstract The process of sperm-egg fusion is critical for successful fertilization, yet the underlying mechanisms that regulate these steps have remained unclear in vertebrates. Here, we show both mouse and zebrafish DCST1 DCST2 are necessary sperm to fertilize egg, similar their orthologs SPE-42 SPE-49 C. elegans Sneaky D. melanogaster . Mouse Dcst1 Dcst2 single knockout (KO) able undergo acrosome reaction normal relocalization IZUMO1, an essential factor fusion, equatorial segment. While KO...
The maternal-to-zygotic transition (MZT) is a key developmental process in metazoan embryos that involves the activation of zygotic transcription (ZGA) and degradation maternal transcripts. We employed metabolic mRNA sequencing (SLAMseq) to deconvolute compound embryonic transcriptome zebrafish. While mitochondrial transcripts prevail prior MZT, we uncover spurious hundreds short intron-poor genes as early 2-cell stage. Upon ZGA, most originate from thousands maternal-zygotic (MZ) are...
The maintenance of specific gene expression patterns during cellular proliferation is crucial for the identity every cell type and development tissues in multicellular organisms. Such a memory function conveyed by complex interplay Polycomb Trithorax groups proteins (PcG/TrxG). These exert their at level chromatin establishing maintaining repressed (PcG) active (TrxG) domains. Past studies indicated that core PcG protein potentially associated with or even stage-specific sets accessory...
The organization of nucleosomes influences transcriptional activity by controlling accessibility DNA binding proteins to the genome. Genome-wide nucleosome profiles have identified a canonical at gene promoters, where arrays well-positioned emanate from nucleosome-depleted regions. mechanisms formation and function promoter remain unclear. Here we analyze genome-wide location during zebrafish embryogenesis show that appear on thousands promoters activation zygotic is independent sequence...
Developmental signaling pathways often activate their own inhibitors. Such inhibitory feedback has been suggested to restrict the spatial and temporal extent of or mitigate fluctuations, but these models are difficult rigorously test. Here, we determine whether ability mesendoderm inducer Nodal its inhibitor Lefty is required for development. We find that zebrafish lefty mutants exhibit excess increased specification mesendoderm, resulting in embryonic lethality. Strikingly, development can...
Fertilization is a multistep process that culminates in the fusion of sperm and egg, thus marking beginning new organism sexually reproducing species. Despite its importance for reproduction, molecular mechanisms regulate this singular event, particularly sperm-egg fusion, have remained mysterious many decades. Here, we summarize our current understanding interaction, focusing mainly on mammalian fertilization. Given fundamental yet lack knowledge vertebrates, discuss hallmarks emerging...
The COVID-19 pandemic has demonstrated the need for massively-parallel, cost-effective tests monitoring viral spread. Here we present SARSeq, saliva analysis by RNA sequencing, a method to detect SARS-CoV-2 and other respiratory viruses on tens of thousands samples in parallel. SARSeq relies next generation sequencing multiple amplicons generated multiplexed RT-PCR reaction. Two-dimensional, unique dual indexing, using four indices per sample, enables unambiguous scalable assignment reads...
Abstract tRNA genes exist in multiple copies the genome of all organisms across three domains life. Besides sequence differences copies, extensive post-transcriptional modification adds a further layer to diversification. Whilst crucial role tRNAs as adapter molecules protein translation is well established, whether are actually expressed, and isodecoders play any regulatory only recently being uncovered. Here we built upon recent developments use NGS-based methods for RNA detection...