Reviews & Analysis

Chimeric antigen receptor T cells (CAR-T cells) are often hindered by the concurrent challenges of variable antigen expression patterns and immunosuppressive tumor microenvironments. A new approach enhances CAR-T cells by coexpressing bacterial enzymes that activate prodrugs in high concentrations at the disease site.

The Review summarized the recent progress in chemical probes and drug candidates for epigenetic writer enzymes and discussed the implication of targeting the chromatin regulatory landscape in cancer biology and therapy.

Optogenetic and thermogenetic tools have been limited to applications for single-state control of cellular processes. A single-component optogenetic tool was found to act as both a temperature sensor and a photoreceptor, enabling multi-state control of developmental signaling.

Reliable quantification and tracing of RNA molecules remain challenging goals. A new fluorescent RNA tag, developed based on a natural adenine-sensing riboswitch and named Squash, offers superior imaging properties and accurate quantification in living cells.

The design of biological materials with tunable properties is an emerging challenge for the twenty-first century. A new approach to direct engineered cells to stick together improves biomaterial performance and simplifies self-healing.

The diversity of biological pathways that are regulated by protein post-translational modification with O-GlcNAc requires community engagement to develop and apply tools to probe the biological and disease-relevant functions of these modifications.

To avoid strife at the interface of basic carbon and nitrogen metabolism, Bacillus subtilis has developed a rather combative solution. If needed, its glutamate synthase suppresses conflicting glutamate breakdown by directly binding and immobilizing its metabolic opponent, glutamate dehydrogenase.

The molecular mechanism through which chromatin-bound RNA-binding proteins (chrRBPs) control transcription remains obscure. A new study reveals that chrRBPs can compartmentalize RNA and transcription machinery into a phase-separated condensate, thus modulating gene expression.

Structural biology and resistance analyses reveal the binding mode and the basis for selective inhibition of the ATP synthase rotary motor protein by glycosylated macrolides.

An autocatalytic peptide cyclase defines a new subclass of plant ribosomally synthesized and post-translationally modified peptides (RiPPs). This discovery explains the origins of a large family of cyclic peptides and inspires new tools for mining these RiPPs across the plant kingdom.

Chemoproteomics-enabled identification of the targets of a hydroxylated cholesterol metabolite, 20(S)-hydroxycholesterol, reveals it to be the first reported endogenous ligand of the sigma-2 receptor, a drug target for neurodegeneration and neuropathic pain.

This Review surveys how resistance mutations to small molecules and recent mutagenesis technologies have driven biological discovery across diverse fields of inquiry.

Genetic code expansion is emerging as a promising strategy to precisely regulate protein expression. A new study engineered cells that enabled noncanonical-amino-acid-triggered insulin expression to rapidly regulate blood glucose levels in a diabetic mouse model.

A new study demonstrates that the receptor-binding domain of the SARS-CoV-2 spike protein binds to sialylated glycans, especially glycolipids, to facilitate viral entry, an insight that identifies new potential targets for SARS-CoV-2 interventions.

RNA modifications are emerging regulators of development and disease. A metabolic labeling approach using 5-fluorocytidine (5-FCyd) allows the mechanism-based profiling of several RNA-modifying enzymes and potentially links their activity to novel RNA targets.

Controlled positioning of the mitotic spindle is key to tissue development and homeostasis. A recent study uncovered an EB1 crotonylation event that orchestrates microtubule dynamics in late mitosis, thus ensuring correct division orientation in vertebrate cells.

Prokaryotic genomes are rife with highly similar toxin–antitoxin modules that need to be protected and diversified at the same time. Studies of paralogous modules now reveal how evolution secures insulation between related systems, without compromising toxin inhibition.

Targeting cholecystokinin receptors (CCKRs) signaling has become an attractive therapeutic strategy for many diseases. The description of cryo-EM structures of CCKRs in the active or inactive states reveal the molecular mechanism of ligand recognition and G-protein-coupling promiscuity.

Escherichia coli are a common component of the human microbiota, producing a diverse collection of small molecules that regulate intra- and interspecies interactions, including those with other microorganisms and with the host.

This Review article explores how uncovering phenotypes linked to the human microbiome often progresses from correlative studies to studies in germ-free animals and fecal microbiota transplants and, finally, to identification of strains and molecules.