Research Briefing

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  • We developed click editors, comprising HUH endonucleases, DNA-dependent DNA polymerases and CRISPR–Cas9 nickases, which together enable programmable precision genome engineering from simple DNA templates.

    Research Briefing
  • Improving the precision of gene correction through RNA base editing typically involves a trade-off with efficiency. We find using G•U wobble base pairs is a universally applicable strategy to improve editing precision and efficiency, and is effective in a mouse model of Rett syndrome in vivo.

    Research Briefing
  • Lab-grown ‘mini-colons’ enable the simulation of colorectal tumor dynamics and the high-resolution study of interactions with cells from the tumor’s native microenvironment. These next-generation organoids offer a wealth of new experimental opportunities, propelling the frontiers of cancer modeling in multiple directions.

    Research Briefing
  • We developed SynTracker, a tool to track conspecific microbial strains using genome synteny. SynTracker is sensitive to genomic structural variation but not to single-nucleotide polymorphisms (SNPs). Combining SynTracker with methods for tracking strains using SNP profiles, we were able to detect species evolving by accumulating predominantly SNPs or predominantly structural variants.

    Research Briefing
  • By integrating confocal illumination along a moving axis with scanning light-field microscopy, confocal scanning light-field microscopy captures images with high spatiotemporal resolution and optical sectioning simultaneously, with low phototoxicity. This compact technique enabled us to investigate a wide variety of rapid subcellular 3D dynamics in vivo with high fidelity over extended periods.

    Research Briefing
  • To advance the toolset for controlling plant gene expression, we developed a CRISPR interference-based platform for the construction of synthetic Boolean logic gates that is functional in multiple plant species. These genetic circuits are programmable and reversible in nature, which will enable spatiotemporal control of plant responses to dynamic cues.

    Research Briefing
  • The replicational age of single cells provides a temporal reference for tracking cell fate transition trajectories. The computational framework EpiTrace measures cell age using single-cell ATAC-seq data, specifically by considering chromatin accessibility at clock-like genomic loci, enabling the reconstruction of the history of developmental and pathological processes.

    Research Briefing
  • A set of 20 computational metrics was evaluated to determine whether they could predict the functionality of synthetic enzyme sequences produced by generative protein models, resulting in the development of a computational filter, COMPSS, that increased experimental success rates by 50–150%, tested in over 500 natural and AI-generated enzymes.

    Research Briefing
  • Borderlands Science is a casual mini-game released within a mass-market video game that crowdsources the alignment of one million RNA sequences from the human microbiome. In 3 years, 4 million participants generated over 135 million puzzle solutions that were used to build a reference alignment and improve microbial phylogeny.

    Research Briefing
  • Cells interact with their local environment to enact global tissue function. By harnessing gene–gene covariation in cellular neighborhoods from spatial transcriptomics data, the covariance environment (COVET) niche representation and the environmental variational inference (ENVI) data integration method model phenotype–microenvironment interplay and reconstruct the spatial context of dissociated single-cell RNA sequencing datasets.

    Research Briefing
  • The underrepresentation of functional glial cells is a major challenge in brain organoid models. We developed an astroglia-enriched cortical organoid model that allows efficient generation of functional astrocytes and enables the formation of astroglial morphological subclasses with layer-specific gene expression profiles upon transplantation into the mouse brain.

    Research Briefing
  • The Iniquitate pipeline assessed the impacts of cell-type imbalance on single-cell RNA sequencing integration through perturbations to dataset balance. The results indicated that cell-type imbalance not only leads to loss of biological signal in the integrated space, but also can change the interpretation of downstream analyses after integration.

    Research Briefing
  • By applying the logic of conditional enzymes, we have developed a zinc-finger-dependent recombinase system, the editing activity of which is induced by zinc finger DNA binding. The system combines the precision of recombinases with the DNA target site programmability of zinc finger domains.

    Research Briefing
  • Many questions on the activity of the Ras proto-oncogene are unanswered due to the lack of tools for detecting active Ras in living cells. Here, we used protein design and structure prediction algorithms to develop biosensors that detect the activity and environment of endogenous Ras.

    Research Briefing
  • Mapping higher-order RNA structures and intermolecular RNA–RNA interactions throughout the transcriptome is critical for understanding RNA functions. We developed KARR-seq, a chemical-assisted RNA proximity capture and sequencing technology that enables sensitive and accurate detection of the RNA structurome and functional RNA–RNA interactions.

    Research Briefing