Crowdsourced riboregulators reveal design principles for programmable RNA switching

RNA-based sensors offer powerful and programmable control of gene expression, yet our understanding of the structural principles that govern their potential design space remains incomplete. Here, we c...

biorxiv.org

Machine Learning Models for Local Optimization of Red Fluorescent Protein Variants in a Low-Data Setting

Fluorescent proteins (FPs) are widely used reporters for visualizing cellular structures and processes. Traditional wet-lab strategies for FP engineering (rational design and directed evolution) have ...

pubs.acs.org

Granular component sub-phases direct ribosome biogenesis in the nucleolus

Dogra et al. use super-resolution microscopy to uncover the molecular origins of spatial heterogeneity in the nucleolar granular component (GC). They show that differential interactions of nucleolar p...

cell.com

De novo design of peptides localizing at the interface of biomolecular condensates - Nature Communications

Combining high-throughput molecular simulations, machine learning, and mixed-integer linear programming, the authors design peptides that localize to condensate interfaces, revealing surfactant-like, ...

nature.com

Contextualised real-time mass spectrometry improves glycosylation detection and characterisation

Glycosylation is a structurally diverse, non-template-driven modification whose analysis by liquid chromatography-mass spectrometry is constrained by discovery-mode acquisition rules developed for pro...

biorxiv.org

Membrane protein solubilization and structure determination using de novo–designed proteins

Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a gener...

science.org

Engineered circular RNA compatible with complete nucleoside modification and rolling circle translation through a Cap-independent translation enhancer - Nature Biomedical Engineering

A suite of tools to improve translation and immunogenicity of circular RNAs, including nucleoside modification and rolling circle translation, for applications in cancer vaccines, protein replacement ...

nature.com

Active-learning-guided optimization of cell-free systems for genome-wide transcriptomic profiling reveals progressive layers of regulation - Nature Communications

Cell-free is a powerful platform to unravel biological complexity. Here, the authors used active learning to optimize buffer composition, boosting mRNA 20-fold, enabling cell-free transcriptomics and ...

nature.com

Decentralized molecular diagnostics for viral diseases - Nature Reviews Bioengineering

Viral diseases continue to impose a major global health burden, yet substantial inequities in access to accurate molecular diagnostics persist, limiting effective surveillance and response. This Revie...

nature.com

Development of a High-Throughput Size-Exclusion Chromatography–Mass Spectrometry Workflow for Real-Time Monitoring of Bioconjugation of Cysteine-Based Antibody–Drug Conjugates

The manufacturing of cysteine-based antibody–drug conjugates (ADCs) requires precise control of the drug-to-antibody ratio (DAR), a critical quality attribute influencing product safety and efficacy. Conventional analytical techniques used for DAR determination, such as hydrophobic interaction chromatography (HIC) and reversed-phase high-performance liquid chromatography (RP-HPLC), are low-throughput and unsuitable for real-time process monitoring, limiting process development efficiency. To address this challenge, we developed a high-throughput size-exclusion chromatography–mass spectrometry (SEC-MS) workflow with and without postcolumn denaturation (PCD) functionality, enabling real-time monitoring of both reduction and conjugation kinetics during cysteine-based ADC manufacturing. Using a short SEC column coupled to a mass spectrometer, analysis time can be performed under 2 min per sample. This workflow was applied to rapidly optimize critical process parameters, including reductant concentration and pH during reduction, and drug-linker ratio during conjugation. The approach provided deeper mechanistic insights into reaction kinetics and supports process analytical technology (PAT)-enabled strategies for advanced process control. Overall, this high-throughput SEC-MS workflow accelerates ADC development while improving manufacturing robustness.

pubs.acs.org

The biology of jumbo phages - Nature Communications

Jumbo phages are bacterial viruses with double-stranded DNA genomes exceeding 200 kb. In this Review, Sam van Beljouw & Li Yuping examine the biology of these bacteriophages, highlighting their di...

nature.com

High-throughput functional profiling and evolutionary covariation analysis of entire riboswitch sequences

Abstract. Riboswitches are useful models for revealing how some RNA molecules undergo dynamic rearrangements of their structures to perform cellular functi

academic.oup.com

Structural modularity of receptor-binding proteins underlies host-range strategy diversification in Klebsiella pneumoniae phages

Bacteriophage receptor-binding proteins (RBPs) determine bacterial host recognition and are central to phage host-range evolution, yet the structural principles governing how RBPs diversify and expand...

biorxiv.org

Rapid Affinity Characterization of Cell-Free Expressed Nanobodies Directly in Lysate with Biolayer Interferometry via Antigen-Immobilized Biosensors

There have been a few recent works showing the advantages of combining cell-free protein expression (CFE) with biolayer interferometry (BLI) for the rapid kinetic characterization of novel capture pro...

pubs.acs.org

AlloGen: Conformation-Selective Binder Generation with Differential State Scoring

Protein binder design has largely optimized for affinity alone, leaving conformational selectivity unaddressed: for allosteric targets such as kinases, nuclear receptors, and GPCRs, a binder that enga...

arxiv.org

mRNAutilus: Multi-Objective-Guided Discrete Generation of mRNA with Optimized Therapeutic Properties

Therapeutic mRNA design requires coordinating multiple interacting sequence features across the full transcript, where codon usage, untranslated regions (UTRs), and their coupling jointly determine st...

arxiv.org

Stabilization strategies and advancements in lyophilization to preserve integrity and efficacy of next-generation biologicals

The success of mRNA-lipid nanoparticles (LNPs) vaccines during the COVID-19 pandemic has significantly increased global demand for stable, thermo-resi…

sciencedirect.com

Less Is More: A Minimal Approach to Synthetic Cell Constriction

Researchers have developed and optimised a minimal system capable of inducing the constriction of synthetic vesicles, representing a significant step forward in synthetic cell division

edu.nl

Is faster always better? A critical assessment of Vibrio natriegens as microbial host for recombinant protein production - Bioprocess and Biosystems Engineering

The marine bacterium Vibrio natriegens has emerged as a promising candidate for recombinant protein production, primarily due to its rapid growth rate combined with its high protein synthesis capacity...

link.springer.com