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Biology subjects

Swett, A.

Publications and source records attributed to Swett, A..

2 recordsLinked to original sources

A Nanoscale Jitterbug Transformer from DNA

Many viruses have intricate polyhedral shells capable of symmetric transformations in response to external stimuli to initiate payload release. Such deployable auxetic nanostructures are not available in the synthetic realm. Here we present a nanoscale Jitterbug transformer using DNA origami that can reconfigure its structure upon chemical and optical signals while maintaining a Poissons ratio of -1. By leveraging molecular dynamics simulations, we design the Jitterbug DNA to form a compact octahedron by storing elastic energy and spontaneously transition into an expanded cuboctahedron by releasing it. DNA transformers are explored like viruses that can create nanopores on lipid membranes and regulate payload release into vesicles. This work integrates programmable DNA self-assembly with free-energy-guided mechanical design, providing a pathway toward adaptive nanomaterials with potential in synthetic organelles and stimuli-responsive nanodevices.

biophysics↗

Genotype-to-phenotype mapping of somatic clonal mosaicism via single-cell co-capture of DNA mutations and mRNA transcripts

Somatic mosaicism is a hallmark of malignancy that is also pervasively observed in human physiological aging, with clonal expansions of cells harboring mutations in recurrently mutated driver genes. Bulk sequencing of tissue microdissection captures mutation frequencies, but cannot distinguish which mutations co-occur in the same clones to reconstruct clonal architectures, nor phenotypically profile clonal populations to delineate how driver mutations impact cellular behavior. To address these challenges, we developed single-cell Genotype-to-Phenotype sequencing (scG2P) for high-throughput, highly-multiplexed, single-cell joint capture of recurrently mutated genomic regions and mRNA phenotypic markers in cells or nuclei isolated from solid tissues. We applied scG2P to aged esophagus samples from five individuals with high alcohol and tobacco exposure and observed a clonal landscape dominated by a large number of clones with a single driver event, but only rare clones with two driver mutations. NOTCH1 mutants dominate the clonal landscape and are linked to stunted epithelial differentiation, while TP53 mutants and double-driver mutants promote clonal expansion through both differentiation biases and increased cell cycling. Thus, joint single-cell highly multiplexed capture of somatic mutations and mRNA transcripts enables high resolution reconstruction of clonal architecture and associated phenotypes in solid tissue somatic mosaicism.

genomics↗