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Deciphering the features, structure, and functions of the cell niche in tissues remains a major challenge. Here, we present scNiche, a computational framework to identify and characterize cell niches from spatial omics data at single-cell resolution. We benchmark scNiche with both simulated and biological datasets, and demonstrate that scNiche can effectively and robustly identify cell niches while outperforming other existing methods. In spatial proteomics data from human triple-negative breast cancer, scNiche reveals the influence of the microenvironment on cellular phenotypes, and further dissects patient-specific niches with distinct cellular compositions or phenotypic characteristics. By analyzing mouse liver spatial transcriptomics data across normal and early-onset liver failure donors, scNiche uncovers disease-specific liver injury niches, and further delineates the niche remodeling from normal liver to liver failure. Overall, scNiche enables decoding the cellular microenvironm

Trogocytosis, the transfer of plasma membrane fragments during cell–cell contact, offers potential for macromolecular delivery but is limited by the uncertain fate of trogocytosed molecules, restriction to membrane cargo and unclear generalizability. Here we demonstrate that donor cells engineered with designed receptors specific to surface ligands can transfer proteins to recipient cells through direct contact. We identified key engineering principles for enhancing transfer and ensuring cargo functionalization, including receptor design, pH-responsive membrane fusion, inducible cargo localization and release, and subcellular translocation. The method is broadly applicable across diverse cell types and operates through a dynamin- and endosome acidification-dependent pathway. Exploiting these findings, we developed TRANSFER, a versatile delivery system with programmable cell type specificity and tunability. TRANSFER can sense multiple ligand inputs, deliver large therapeutic protein car

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The complexity of the cellular proteome is massively expanded by a repertoire of chemically distinct reversible post-translational modifications (PTMs) that control protein localisation, interactions, and function. The temporal and spatial control of these PTMs is central to organism physiology, and mis-regulation of PTMs is a hallmark of many diseases. Here we present an approach to manipulate PTMs on target proteins using nanobodies fused to enzymes that control these PTMs. Anti-GFP nanobodies fused to thioesterases (which depalmitoylate protein cysteines) depalmitoylate GFP tagged substrates. A chemogenetic approach to enhance nanobody affinity for its target enables temporal control of target depalmitoylation. Using a thioesterase fused to a nanobody directed against the Ca(v)1.2 beta subunit we reduce palmitoylation of the Ca(v)1.2 alpha subunit, modifying the channel’s voltage dependence and arrhythmia susceptibility in stem cell derived cardiac myocytes. We conclude that nanobod

Lasso peptides are a diverse class of naturally occurring, highly stable molecules kinetically trapped in a distinctive [1]rotaxane conformation. How the ATP-dependent lasso cyclase constrains a relatively unstructured substrate peptide into a low entropy product has remained a mystery owing to poor enzyme stability and activity in vitro. In this study, we combined substrate tolerance data with structural predictions, bioinformatic analysis, molecular dynamics simulations and mutational scanning to construct a model for the three-dimensional orientation of the substrate peptide in the lasso cyclase active site. Predicted peptide cyclase molecular contacts were validated by rationally engineering multiple, phylogenetically diverse lasso cyclases to accept substrates rejected by the wild-type enzymes. Finally, we demonstrate the utility of lasso cyclase engineering by robustly producing previously inaccessible variants that tightly bind to integrin αvβ8, which is a primary activator of t

The dynamic study of coacervates in vitro contributes our understanding of phase separation mechanisms in cells due to complex intracellular physiology. However, current researches mainly involve the use of exogenous auxiliary agents to form multi-compartmental coacervates with short-term stability. Herein, we report the endogenous self-organizing of multi-component coacervates (HA/PDDA/BSA/DMAEMA) induced by a dynamic stimulation process of protein-mediated photopolymerization. As polymerization proceeds, the cycled structural evolution and maturation from coacervate droplets into multi-compartmental coacervates, coacervate vesicles and coacervate droplets are revealed, which are driven by electrostatic interaction and osmotic pressure difference supported by dynamic and thermodynamic control. Specially, by regulating the light stimulation time, a type of multi-compartmental coacervates can be widely obtained with high structural stability over 300 days. Being a promising artificial c

SPNS2 exports S1P and FTY720-P to control immune cell migration. Here, the authors use cryo-EM, immunofluorescence, in vitro binding and in vivo S1P export, and MD simulations to uncover the mechanism...

Liquid-liquid phase separation plays an important role in many natural and technological processes. Herein, we implement lateral microphase separation at the surface of oil micro-droplets suspended in water to prepare a range of discrete floating protein/polymer continuous two-dimensional (2D) heterostructures with variable interfacial domain structures and dynamics. We show that gel-like domains of bovine serum albumin (BSA) co-exist with fluid-like polyvinyl alcohol (PVA) regions at the oil droplet surface to produce floating heterostructures comprising a 2D phase-separated protein mesh or an array of discrete mobile protein rafts depending on the conditions employed. Enzymes are embedded in the discontinuous BSA domains to produce droplet-supported microphase-separated 2D reaction scaffolds that can be tuned for interfacial catalysis. Taken together, our work has general implications for the structural and functional augmentation of oil droplet interfaces and contributes to the surf

Agricultural Biotechnology Market growth register a 8.90% CAGR By 2032. Agricultural Biotechnology industry trends By Crop Type, Application, Techniques, top players analysis, regions- forecast 2032.

The genome-editing technology can be supercharged by artificial intelligence—and the results are already being felt.

Belief BioMed and Grand Life Sciences partner to bring BBM-H803 gene therapy to 30,000 hemophilia A patients in China. Here's what it means for treatment access.

Genetically engineered commensal bacteria are promising living drugs, however, their therapeutic molecules are frequently confined to their colonization sites. Herein, we report an oral protein delivery technology utilizing an engineered bacterial type zero secretion system (T0SS) via outer membrane vesicles (OMVs). We find that OMVs produced in situ by Escherichia coli Nissle 1917 (EcN) can penetrate the intact gut epithelial barrier to enter the circulation and that epithelial transcytosis involves pinocytosis and dynamin-dependent pathways. EcN is engineered to endogenously load various enzymes into OMVs, and the secreted enzyme-loaded OMVs are able to stably catalyze diverse detoxification reactions against digestive fluid and even enter the circulation. Using hyperuricemic mice and uricase delivery as a demonstration, we demonstrate that the therapeutic efficacy of our engineered EcN with a modified T0SS outperforms that with a direct protein secretion apparatus. The enzyme-loaded

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Bioptimus, an AI startup located in Paris, has successfully raised $76 million in funding. This milestone marks a significant achievement for the company as it continues to develop its artificial intelligence solutions. The funding is expected to propel its growth and innovation in the competitive tech landscape.