Proteins lacking defined ligandable pockets remain challenging drug targets. Here, we develop a molecular glue-based PROTAC (MGPROTACs) approach that chemically conjugates a molecular glue stabilizer ...

Affinity-selection platforms are powerful tools in early drug discovery, but current technologies such as DNA-encoded libraries (DELs) are limited by synthesis complexity and incompatibility with nucl...

Chemical proteomics has brought rigor to covalent drug discovery and drugs to the clinic. Can it deliver a new generation of drug targets?

Acquisition provides highly differentiated clinical-stage treatment for prostate cancer, building on Johnson & Johnson’s nearly two decades of innovation in the disease area Lead asset shows potential...

In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form thro...

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Previous high-throughput evaluations of CRISPR activities for a large number of target and guide RNA sequences were based on measuring insertion–deletion frequencies rather than cleavage efficiencies. Here we develop two high-throughput in vitro methods, Cut-seq1 and Cut-seq2, to evaluate Cas9 cleavage efficiency for tens of thousands, or even hundreds of thousands, of guide RNA–target pairs. These methods reveal low correlations between in vitro cleavage efficiencies and insertion–deletion frequencies in cells, yet high concordances in protospacer adjacent motif compatibility. Using the resulting large datasets of in vitro cleavage efficiencies, we develop DeepCut, a set of deep learning models that can identify optimized single-guide RNAs that can selectively cleave specific sequences, even in the presence of similar noise sequences. Using these optimized single-guide RNAs, we develop a method, CLOVE-seq (which stands for cleavage for large-scale optimized variant enrichment sequenci

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Schmid and Walter train a classifier that discerns functionally relevant structure predictions in proteome-wide protein-protein interaction (PPI) screens using AlphaFold-Multimer, and they use this co...

Acetyl-coenzyme A functions as a non-canonical signal to trigger mitophagy, and the acetyl-coenzyme A–NLRX1 axis underlies the KRAS-inhibitor-induced mitophagy response and promotes drug resistan...

Abstract. Polyethylene terephthalate (PET)-hydrolyzing enzymes (PETases) are a recently discovered enzyme class capable of plastic degradation. PETases are

In the growing field of chemical proteomics, there is a need for general methods to map the reactivity profiles of covalent probes in complex proteomes. Now, a completely unbiased proteomic workflow h...

McCreery, Stubb et al. show that mechano-osmotic changes in the nucleus induce general transcriptional repression and prime chromatin for cell fate transitions by relieving repression of specific differentiation genes.

Membrane contact sites between the endoplasmic reticulum (ER) and plasma membrane (PM) are essential for lipid transfer, calcium signaling, and membrane organization. While the formation and function of ER–PM contacts are increasingly well-characterized, the spatiotemporal regulation of their localization remains elusive. Emerging evidence using nanopatterned substrates, ultrastructural imaging, and protein localization analyses indicates that membrane curvature can act as a spatial cue for the recruitment of specific tethering proteins, influencing where contact sites form. This opinion article synthesizes recent advances linking membrane topography ER–PM contact organization and highlights systems where curvature actively orchestrates contact position through curvature-sensing proteins. It also outlines key unanswered questions about how membrane curvature integrates into broader signaling networks that govern organelle contact communication.