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 […]
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 […]
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 […]
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 […]
07/2022 - Computational estimation of quality and clinical relevance of cancer cell lines
Immortal cancer cell lines (CCLs) are the most widely used system for investigating cancer biology and for the preclinical development of oncology therapies. Pharmacogenomic and genome-wide editing screenings have facilitated the discovery of clinically relevant gene–drug interactions and novel therapeutic targets via large panels of extensively characterised CCLs. However, tailoring pharmacological strategies in a precision […]
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