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Here the authors introduce a CRISPR-based, dual-fluorescent reporter system in mice, which enables rapid in vivo testing of the effects of human non-coding variants linked to disease, implicating rare and common enhancer variants in autism.

The ExoSloNano system facilitates nanogold probe-based labeling of specific proteins of a wide range of sizes in live cells for cryo-electron tomography and correlative light and electron microscopy studies.

An ‘intracrine’ signaling mechanism is proposed whereby a G-protein-coupled receptor (free fatty acid receptor 4) senses locally released fatty acids on intracellular membranes associated with lipid droplets to efficiently regulate lipolysis in adipocytes.

REXER, a new method that allows long sections of DNA to be inserted or replaced in the genome of the bacterium Escherichia coli, is used to investigate codon replacement schemes for the generation of synthetic genomes.

A chromosome-level genome assembly for the Ninu (greater bilby) and genome sequences for the extinct Yallara (lesser bilby), together with resequenced genomes, shed light on the demographic history of Ninu and inform conservation plans for this culturally and ecologically important marsupial.

Herpesvirales utilize a unique nuclear egress route for capsid export. Here the authors show that herpesviruses exploit a cellular membrane protein, once thought to transport chloride, to facilitate membrane fusion and egress from the nucleus.

Current antimalarials often fail to target mature stage V gametocytes. To aid antimalarial drug discovery, the authors present a preclinical malaria transmission-blocking drug research platform, using engineered parasites, that facilitates the screening for gametocytocidal compounds in vitro and the evaluation of transmission-blocking drug activity in vivo.

Here, the authors identify mechanisms of glycosylation of intrinsically disordered regions present in streptococci membrane proteins, uncovering a functional role for glycosylation in Streptococcus mutans chaperone PrsA.

Nanoparticles are a promising approach to increase immunogenicity of protein antigens for vaccines. Here, Brouwer et al. design self-assembling, two-component protein NPs that present native-like SOSIP trimers of HIV envelope protein and determine immunogenicity in a small animal model.

The efficiency of base editing is substantially increased by optimizing expression and nuclear localization of the editing enzymes.

The in vivo dynamics of bacterial translation initiation has remained unexplored. Here, the authors measured ribosome binding kinetics of the key factors directly inside living E. coli cells, using single-molecule tracking techniques, and found novel link between translation and transcription.

Engineered living materials (ELMs) are emerging as a field at the intersection of materials science and synthetic biology. Here, the authors describe a photosynthetic ELM composed of genetically engineered cyanobacteria in a hydrogel matrix, capable of bioremediation and inducible cell death.

Discovering molecular pathways that sensitize cells to poly(ADP-ribose) polymerase (PARP)- trapping inhibitors is important for anti-cancer therapy. Here, the authors report that inactivation of the CHD6 chromatin remodelling enzyme sensitizes cells to PARP inhibitors via reduced abasic site repair, PARP-1 accumulation on chromatin, and replication stress.

Genetic code expansion and reprogramming require orthogonal tRNAs. Methods have now been developed for the automated generation of chimeric orthogonal tRNAs and discovery of their cognate synthetases. These approaches have been used to discover new orthogonal pairs for efficient non-canonical amino acid incorporation.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

DNA methylation and copy number variant analyses across a large number of genetic mouse models of pediatric brain tumors reveal subtype-specific molecular alterations shared with the corresponding human diseases.

Cas9 DNA targeting is inherently sequence specific but not temporally controlled. Here, authors spatiotemporally couple Cas9 activity to target site transcription in eukaryotes and exploit this to preferentially edit the more highly transcribed of two alleles that harbor identical Cas9 targets.

Current base editors cannot simultaneously edit multiple loci with base-pair level precision, hindering complex genotype generation. Here the authors describe optimized Cas12a gRNA array designs, enabling base-pair conversions at up to 15 loci and with reduced bystander editing rates in human cells.

The volatile odorant 2- methylisoborneol is one of the most abundant terpenoid natural products found in nature. Here, the authors report biochemical and structural data showing that bacterial 2-methylisoborneol biosynthesis is compartmentalized inside a megadalton encapsulin protein compartment.

Bacteroides species are a promising chassis for developing living therapeutics, but this application is challenged by their poorly understood protein secretion abilities. Here, the authors report the discovery, characterization, and implementation of a molecular toolkit that enables efficient protein secretion in Bacteroides species.

Proteolytic activity of the 26S proteasome involves many genes, but how proteasome subunit expression is regulated remains unclear. Here the authors characterise THAP1 as a transcriptional activator of PSMB5, suggesting that proteasome dysfunction might underlie the pathogenesis of THAP1 dystonia.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

Detection of geoneutrinos from ⁴⁰K decay in the Earth would yield a wealth of information on Earth’s bulk chemical composition and radiogenic heat. By exploiting the positron identification ability of LiquidO to reject backgrounds, charged-current neutrino capture reactions on ⁶³Cu is proposed as the ideal way to observe potassium geoneutrinos

Stack pressure controls porosity during Li alloying/dealloying. A threshold pressure is needed for the densification and stable cycling of Li alloys in batteries, leading to the design of Li alloy anodes with densified interfacial layers for cycling at low pressures in solid-state batteries.

A genome-wide CRISPR-based screen of Toxoplasma gondii during mouse infection reveals previously uncharacterized factors contributing to parasite virulence.

The double-strand break sensor MRE11 is identified as a pivotal mediator of cGAS activation in response to multiple types of DNA damage.

Cell-cell fusion is fundamental to physiological processes such as muscle formation and viral infection. Here, the authors show that the proteins embedded on the plasma membrane present a biophysical barrier that can regulate cell-cell fusion.

Engineering mammalian cells with synthetic circuits drives innovation in next-generation biotherapeutics and industrial biotechnology. Here the authors use RNA-seq and computational biology to identify drugs that increase engineered cell productivity without genetic edits - Filgotinib proved enhanced gene expression across contexts, offering a powerful tool for biotech applications.

A bottleneck to engineered multicellular systems is the lack of a scalable signalling language. Here the authors use fungal mating peptide and GPCR pairs to build functional cell-to-cell communication links.