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Quadruplet codons allow multiplexing of non-canonical amino acids within single polypeptides in living cells. We show that including high-usage triplet codons after quadruplet codons can improve their decoding efficiency in genetic circuits, which allowed us to develop a system for the programmable biosynthesis of exotic macrocyclic peptides in cells.
Satellite cells, the stem cells of skeletal muscle, are responsible for muscle development and regeneration. Although low in abundance, satellite cells can be isolated from muscle but cannot be propagated successfully in culture in numbers needed for therapeutic use. We developed a method to generate cells with satellite cell characteristics from skeletal muscle organoid cultures.
The therapeutic principle of allogeneic hematopoietic cell transplantation, one the most common forms of cancer immunotherapy, is alloreactivity, yet its molecular determinants remain largely unknown. An analytical framework now enables personalized assessment of alloreactivity from whole-exome sequencing of donor–recipient pairs, to help with prognostication of disease relapse and immune-mediated complications.
We have discovered an effect, termed stacking-induced intermolecular charge transfer-enhanced Raman scattering (SICTERS), that enhances the Raman signal intensities of small molecules by relying on their self-stacking rather than external substrates. This effect enables the design of substrate-free small-molecule probes for high-resolution, non-invasive transdermal Raman imaging of lymphatic drainage and microvessels.
To handle increasingly large protein databases, a new ultrafast, highly sensitive method — Dense Homolog Retriever (DHR) — detects remote homologs using dense retrieval and protein language models. Its alignment-free nature makes it much faster than traditional approaches, and the newly found remote homologs benefit our understanding of protein evolution, structure and function.
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.
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.
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.
We use a CRISPR screening platform based on adeno-associated virus and the Sleeping Beauty transposon (AAV-SB-CRISPR) to perform in vivo CRISPR screens in primary natural killer (NK) cells across four different tumor models, and identify calcium homeostasis modulator family member 2 (CALHM2) as an NK cellular checkpoint protein.
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.
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.
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.
