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A chemical genomics approach was used to identify regulators of drug sensitivity for pyrvinium, a cytotoxic agent with anti-cancer potential, revealing mitochondrial complex I sensitivities and a role for C1orf115 in regulating ABCB1 activity.
Bicyclostreptins are peptide natural products in which a macrocyclic β-ether and a heterocyclic sp3–sp3 linkage between a backbone amide nitrogen and an adjacent α-carbon are installed by two radical S-adenosylmethionine metalloenzymes.
A combination of mass spectrometry, pooled genome screens and STRING analysis identifies key uptake mediating interactions between nanoparticle-adsorbed proteins and cells via the low-density lipoprotein receptor.
Metabokiller is a novel, explainable AI-backed method for carcinogenicity prediction that leverages the biological and chemical properties associated with carcinogens.
Merging the generalized extracellular molecule sensor (GEMS) system with screening designed ankyrin repeat proteins (DARPins) identifies an advanced modular bispecific extracellular receptor (AMBER) for detection of fibrinogen degradation products.
A FRET-based assay using the conserved tryptophans of bacterial quorum-sensing LuxR-type proteins and synthetic fluorophore-acyl-homoserine lactone conjugates enables measurement of ligand-binding affinities either in vitro or in cells.
A hypercompact adenine base editor termed TaRGET-ABE was developed by fusing a catalytically inactive transposon-associated transposase B guided by an engineered RNA to deaminases, which achieves efficient A-to-G conversions via adeno-associated viral delivery in mammalian genomes.
Only one protein factor is known that senses Na+ and controls gene expression. The Breaker Laboratory describes a bacterial riboswitch class selective for Na+ that regulates genes important for Na+ homeostasis, pH maintenance, osmotic stress response and ATP synthesis.
Using a Cas13d-based nanosystem to knockdown lung protease cathepsin L, Cui et al. demonstrated that CRISPR–Cas system can be used to prevent and treat SARS-CoV-2 infection by targeting mRNA of host genes.
Kras activation in pancreatic cancer cells induced O-GlcNAc modification of malate dehydrogenase 1, regulating glutamine metabolism and promoting tumor growth.
A combination of solubility proteome profiling with phosphoproteomics enables systematic analysis of the phosphorylation status of proteins in soluble and condensate-bound pools.
pChem is a computational tool that provides a pipeline for performance assessment of chemoproteomic probes, with the ability to score the profiling efficiency, modification homogeneity and proteome-wide residue selectivity of a tested probe.
The discovery of a strained β-lactone electrophile that covalently targets a KRAS G12 somatic mutation and acylates the mutant serine to suppress oncogenic signaling.
Using single-molecule magnetic tweezers and biochemical methods, Naqvi et al. revealed how CRISPR–Cas12a regulates the DNA cleavage rate through a conserved stacking interaction between the R-loop and the W355 residue and the sequence of the CRISPR RNA 3′ end.
Evolink, a method developed to co-evolve structurally adjacent but sequence-distant sites in molecular machines, was used in concert with computational modeling to evolve an improved tethered ribosome variant.
The de novo design of a pair of complementary peptides, one basic for cell penetration and target binding and one acidic that can be fused to proteins of interest, provides an approach for delivery into mammalian cells and subcellular targeting.
A combination of engineering a fluorine-selective trans-acyltransferase and manipulation of the fluorinated extender unit pool in Escherichia coli enables the production of site-selectively fluorinated erythromycin precursors in vitro in vitroin vitro and in vivo.
A combined screening and selection approach enables the evolution of the generalist transcription factor RamR into specific and sensitive biosensors for various alkaloids and in turn a streamlined pathway for tetrahydropapaverine biosynthesis.
Functional screening of a large metagenomic library with a droplet microfluidics platform enabled the discovery of SN243, a bacterial β-glucuronidase from the glycoside hydrolase 3 family, which was characterized structurally and biochemically.
The marine compound microcolin B stimulates the Hippo pathway and selectively kills YAP-dependent cancer cells by inhibiting phosphatidylinositol transfer protein and depleting plasma membrane phosphatidylinositol-4-phosphate.