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08/2022 - The Molecular Structure of Anterograde Intraflagellar transport trains

Anterograde intraflagellar transport trains are essential for cilia assembly and maintenance. These trains are formed of 22 IFTA and IFTB proteins that link structural and signalling cargoes to microtubule motors for import into cilia. It remains unknown how the IFTA/B proteins are arranged into complexes and how these complexes polymerise into functional trains. Here, we […]

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07/2022 - Reduced gene templates for supervised analysis of scale-limited CRISPR-Cas9 fitness screens

Pooled genome-wide CRISPR-Cas9 screens are furthering our mechanistic understanding of human biology and have allowed us to identify new oncology therapeutic targets. Scale-limited CRISPR-Cas9 screens—typically employing guide RNA libraries targeting subsets of functionally related genes, biological pathways, or portions of the druggable genome—constitute an optimal setting for investigating narrow hypotheses and are easier to execute […]

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07/2022 - In situ architecture of the ciliary base reveals the stepwise assembly of intraflagellar transport trains

The cilium is an antenna-like organelle that performs numerous cellular functions, including motility, sensing, and signaling. The base of the cilium contains a selective barrier that regulates the entry of large intraflagellar transport (IFT) trains, which carry cargo proteins required for ciliary assembly and maintenance. However, the native architecture of the ciliary base and the […]

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07/2022 - Recombination of repeat elements generates somatic complexity in human genomes

Non-allelic recombination between homologous repetitive elements contributes to evolution and human genetic disorders. Here, we combine short- and long-DNA read sequencing of repeat elements with a new bioinformatics pipeline to show that somatic recombination of Alu and L1 elements is widespread in the human genome. Our analysis uncovers tissue-specific non-allelic homologous recombination hallmarks; moreover, we […]

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07/2022 - Efficient precision genome editing of Chlamydomonas reinhardtii with CRISPR/Cas

CRISPR/Cas genome engineering in the unicellular green algal model Chlamydomonas reinhardtii has until now only been applied to targeted gene disruption, whereas scar-less knock-in transgenesis has generally been considered infeasible. We have developed highly efficient homology-directed knock-in mutagenesis in cell-walled strains of Chlamydomonas. Our method allows scarless integration of fusion tags and sequence modifications of near arbitrary proteins […]

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