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Biology subjects

Lindeman, A.

Publications and source records attributed to Lindeman, A..

2 recordsLinked to original sources

DRUG-seq Provides Unbiased Biological Activity Readouts for Drug Discovery

Unbiased transcriptomic RNA-seq data has provided deep insights about biological processes. However, its impact in drug discovery has been narrow given high costs and low throughput. Proof-of-concept studies with Digital RNA with pertUrbation of Genes (DRUG)-seq demonstrated the potential to address this gap. We extended the DRUG-seq platform by subjecting it to rigorous testing and by adding an open-source analysis pipeline. The results demonstrate high reproducibility and ability to resolve the mechanism(s) of action for a diverse set of compounds. Overall, the protocol and open-source analysis pipeline are a step towards industrializing RNA-seq for high complexity transcriptomics studies performed at a saturating scale.

genomics↗

A genome-wide CRISPR screen identifies ZCCHC14 as a host factor required for hepatitis B surface antigen production

GRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/718940v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (45K):\norg.highwire.dtl.DTLVardef@1782e32org.highwire.dtl.DTLVardef@120f111org.highwire.dtl.DTLVardef@1b2ad50org.highwire.dtl.DTLVardef@1907bc1_HPS_FORMAT_FIGEXP M_FIG C_FIG SUMMARYA hallmark of chronic hepatitis B virus (CHB) infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A novel small molecule RG7834 has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase protein 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential novel host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identified novel factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients.

microbiology↗