RNA is frequently chemically modified, with over 170 types of chemical modifications identified to date in cellular RNAs. These modifications, along with their effector proteins, constitute new layers of gene expression regulation by controlling either the fate of modified RNAs at nearly every stage of their life cycle or local transcription through modulating the nearby chromatin state and transcriptional complexes. This is especially evident in dynamic biological contexts such as cellular state transitions, signaling, immune responses, and stress adaptation.

Development of an ERAD-hijacking technology overcomes the challenges of current targeted protein degradation approaches to achieve degradation of transmembrane proteins.

Leigh syndrome is a severe and untreatable mitochondrial disease. Using patient-derived models in 2D and 3D, Zink and colleagues identify the PDE5 inhibitor sildenafil as a repurposable drug candidate, leading to lifespan extension in mammalian models and clinical improvement in six individuals with Leigh syndrome.

Human-specific transcriptomic and regulatory features are present in the cerebellum, with ZP2 playing a key role in synapse regulation. ZP2 expression is induced by pontine mossy fibers, leading to decreased synaptic proteins and neuronal activity, which provides insights into the evolutionary development of the human cerebellum.

Optovolution leverages optogenetics and the yeast cell cycle to impose rapid, tunable selection, enabling the continuous evolution of light-responsive regulators, logic gates, and other complex protein behaviors that were previously difficult to evolve.

β-hydroxybutyrate (BHB), the ketone body associated with a ketogenic diet, metabolically reprograms and fuels CAR T cells to achieve proliferation, cytokine production, and superior tumor control. These findings suggest that BHB supplementation may be a practical way to boost adoptive cancer immunotherapy.

Whole-organ and whole-body atlases at single-cell resolution enable quantitative cellome-wide analysis across development, physiology, and pathology.

LUMI lab is a foundation model-driven self-driving platform that autonomously discovers ionizable lipids for mRNA delivery. Iterative active learning uncovered brominated tails as a potent structural motif that enables efficient and safe pulmonary mRNA delivery.

Equipping T cells with fungal enzymes to utilize cellobiose (a safe and natural disaccharide of glucose obtained from the wood polymer cellulose) enhances their viability and effector function in tumor microenvironments where glucose concentrations are constrained.

Histidine scanning represents a broadly applicable technique for the identification of critical interaction sites within TCRs and other mechanosensory receptors to enhance receptor signaling strength and augment therapeutic efficacy via the catch bond mechanism.

The clock component CCA1 functions as a molecular rheostat, fine-tuning cell-type-specific electrochemical gradients to optimize carbon allocation and the timely coordination of shoot and root growth balance.

A global genomic survey of infant gut bifidobacteria shows that B. infantis remains highly prevalent and diverse in infants from low- and middle-income countries but scarce in Western, industrialized populations and poorly represented in current probiotics. This genomic and culture collection catalogs geo-specific B. infantis strains and provides a blueprint for developing probiotics tailored to local diets and populations to support infant health.

Human pancreatic cancer cells sense specific components of the ECM to fine-tune their autophagy flux levels, conferring the ability to coordinate proliferation, survival, and responsiveness to chemotherapy. Targeting ECM sensing may turn this ability into a therapeutic opportunity.

In a preclinical breast cancer metastasis model, the same bacteria strain, when present intracellularly versus extracellularly, exerts opposing effects on tumor immunity by inducing divergent neutrophil states, highlighting the intricacy in bacterial-host engagement for shaping tumor immunity.

Integration of electrophysiology with single-cell transcriptomics defines the molecular signature of human dermal sleeping nociceptors and reveals oncostatin M as a selective modulator of these neurons in humans, providing a therapeutic entry point for neuropathic pain.