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

Restoring intracellular homeostasis disrupted by synthetic nanoassemblies - Nature Chemical Biology

Cells have evolved defense pathways to maintain homeostasis against external perturbations, but not against new-to-nature nanomaterials, which can irreversibly accumulate and induce cell stress. Now, ...

doi.org

Rational design of disordered proteins for sequence–function investigation - Nature

GOOSE enables the design and testing of thousands of disordered protein region sequences to reveal distinct sequence-to-function relationships.

nature.com

Quantifying phage-host dynamics using droplet microfluidics - Nature Communications

Bacteriophages are key tools in molecular biology and promising agents against antibiotic-resistant bacteria. Here, the authors present a high-throughput droplet microfluidics platform that co-encapsu...

doi.org

xDecoder unlocks the potential of genomic foundation models for few-shot personal gene expression prediction - Molecular Systems Biology

Large-scale genomic language models (gLMs) hold promise for modeling gene regulation, yet their ability to capture personal gene expression variations remains unresolved. We developed xDecoder, a unified decoding framework that utilizes gLMs and sequence-to-function (S2F) embeddings to learn how personal genetic variation shapes gene expression from paired genome-transcriptome data. Compared to the pretrained genomic models, xDecoder with personalized DNA–RNA training makes cross-individual prediction tractable for seen genes in a few-shot setting. However, zero-shot prediction at unseen loci remains unreliable and gene-dependent, revealing a cross-locus transfer bottleneck of current sequence models. Experiments incorporating individual-level chromatin accessibility suggested that regulatory-state information important for unseen-locus prediction is not fully captured by current DNA-only models. Overall, these results highlight the potential utility of the few-shot setting, the limitations of DNA-only models, and point toward multi-omic, variant-aware frameworks as a promising direction for building personalized regulatory models.

doi.org

Design-driven optimization of low-cost reagent formulations for reproducible and high-yielding cell-free gene expression - Nature Communications

Recombinant proteins are a crucial product for basic science, biotechnology research, and biomanufacturing. Here, the authors develop a robust, low-cost, and high-yielding cell-free platform for prote...

nature.com

J. Craig Venter 1946–2026 - Nature Biotechnology

Nature Biotechnology - J. Craig Venter 1946–2026

nature.com

PNAS

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

edu.nl

Apply for Anthropic’s AI for Science rare disease research grants

Anthropic is sharing a focused call for AI for Science applications centered specifically on rare genetic diseases. Accepted applicants will receive up to $50,000 in Claude credits over six months, with the goal of building a community of researchers looking into how AI can reshape our understanding of rare disease.

anthropic.com

AllTheBacteria: a community resource empowers biology and discovers novel peptide antibiotics

Public microbial genomes encode an immense record of biological diversity, evolution and molecular function, but much of this information remains difficult to reuse because raw sequencing data are not...

biorxiv.org

Synthetic biology in action: maturing tools and their potential

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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

Phosphoserine as an Alternative Energy Source for E. coli Cell-Free Protein Synthesis with Increased Yield and Prolonged Activity

Energy-supplying molecules are essential for biological processes, particularly for transcription and translation. Cell-free protein synthesis (CFPS) systems are powerful tools for in vitro protein pr...

pubs.acs.org

Genetic manipulation of a giant virus-associated virophage

Virophages are double-stranded DNA viruses that hyperparasitize giant viruses infecting unicellular eukaryotes. Parasitization by virophages often reduces the replication of giant viruses, thereby modulating microbial communities in the environment. However, the molecular mechanisms underlying the tripartite relationship are largely unknown due to methodological limitations. In the present study, we developed a reverse-genetics system for a Sputnik virophage that parasitizes the amoeba-infecting giant virus, mimivirus. We demonstrated that transfection of genomic DNA could recover infectious virophage particles. Transfection of genomic DNA synthesized by circular polymerase extension reaction (CPER) also resulted in the recovery of infectious viruses. As a proof of concept, we successfully modified two Sputnik genes by transfecting CPER-assembled mutant genomic DNA. Collectively, our reverse-genetics system provides a framework for assessing the functional importance of Sputnik genes and should facilitate future genetic studies of virophages. ### Competing Interest Statement The authors have declared no competing interest. Japan Society for the Promotion of Science, https://ror.org/00hhkn466, 25K18450, 22K15175, 22H00384 Japan Science and Technology Agency, JPMJAX22BI

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