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Biology subjects

Brannon, C. M.

Publications and source records attributed to Brannon, C. M..

4 recordsLinked to original sources

An Advanced Mobile Laboratory to enable field-based microbial ecology and cell biology across scales

Microbial biodiversity is central to ecosystem function, yet mechanistic insights into the cell biology of environmental organisms remain limited. The underlying challenges are twofold: most microbes remain uncultivable, and a persistent gap exists between field sampling and laboratory analyses. Here, we introduce the Advanced Mobile Laboratory (AML), a field-deployable platform that integrates confocal microscopy, image-enabled cell sorting, and cryo-preparation for expansion and electron microscopy. This setup enables immediate, standardized processing and analysis of environmental communities directly at the sampling site. We demonstrate its capability using marine eukaryotic plankton, showing how the AML enables multiscale investigations, from live imaging of natural communities to enabling ultrastructural and single-cell omics analyses, while minimizing sample degradation and enabling on-site experimentation. By bringing high-end sample preparation and analytical capacity into the field, the AML enables studying life in its natural context to mechanistically understand lifes diversity in the environment.

cell biology↗

Creased ciliary flocks shape unfolding dynamics via information bottlenecks in an aneural animal

Multicellular organisms utilize thin sheet folding to achieve functional three-dimensional forms. During embryonic development, stereotypical epithelial folds emerge from active cellular and molecular processes including cell shape change and differential cell growth. Active thin sheet folding promises to be a powerful design technique in the fields of active solids, soft robotics, and synthetic biology. However, the general principles of active thin sheet folding remain poorly understood. Here we discover a non-canonical cilia-driven thin sheet folding behavior exhibited by basal animal Trichoplax adhaerens. Through volumetric imaging, we found that, despite having no nervous system, T. adhaerens has the remarkable ability to resolve complex body folding states in a non-stereotypical fashion using a carpet of collectively flocking cilia. Cilia-resolved imaging revealed that folds create crease defects in the animals ciliary carpet, which act as information bottlenecks to break collective behavior of cilia. In turn, these bottlenecks enable the disjointed locomotion required for fold removal. These findings point to a two-way coupling mechanism, wherein ciliary activity shapes the animals folding state and vice versa. Our work demonstrates the broad configuration space of non-stereotypical active folding and highlights the power of distributed activity to drive folding and unfolding of a thin multicellular sheet. We anticipate our study to be a starting point for the establishment of a new class of distributed active origami wherein fold lines themselves are dynamic and motile, with implications in engineering of self-folding materials. Additionally, our work reveals a new facet of the Placozoan behavioral repertoire, which extends our understanding of mechanical intelligence in the absence of a nervous system.

biophysics↗

Algorithmic construction of topologically complex biomineral lattices via cellular syncytia

Biomineralization is ubiquitous in both unicellular and multicellular living systems [1, 2] and has remained elusive due to a limited understanding of physicochemical and biomolecular processes [3]. Echinoderms, identified with diverse architectures of calcite-based structures in the dermis[4], present an enigma of how cellular processes control shape and form of individual structures. Specifically, in holothurians (sea cucumbers), multi-cellular clusters construct discrete single-crystal calcite ossicles ([~] 100 {micro}m length scale), with diverse morphologies both across species and even within an individual animal [5]. The local rules that might encode these unique morphologies in calcite ossicles in holothurians remain largely unknown. Here we show how transport processes in a cellular syncytium impart a top-down control on ossicle geometry via symmetry breaking, branching, and fusion in finite cellular clusters. As a unique example of cellular masonary, we show how coordination within a small cluster of cells builds calcite structures about an order of magnitude larger than any individual participating cell. We establish live imaging of ossicle growth in Apostichopus parvimensis juveniles revealing how individual crystalline seeds ([~] 1 - 2 {micro}m) grow inside a multi-cellular syncytial complex with the biomineral completely wrapped within a membrane-bound cytoplasmic sheath. Constructing a topological description of ossicle geometries from 3D micro-CT (computational tomography) data reveals the hidden growth history and conserved patterns across ossicle types. We further demonstrate vesicle transport on the surface of the ossicle, rather than cell motility, regulates material transport to the ossicle tips via a unique cytoskeletal architecture. Finally, using reduced order models of conserved transport on self-closing active branching networks, we highlight the hidden universality in the growth process of distinct ossicles. The system presented here serves as a unique playground merging top-down cellular physiology and classical branching morphogenesis [6] with bottom-up non-equilibrium mineralization [7] processes at the interface of living and non-living matter [8].

biophysics↗

A genome-wide atlas of recurrent repeat expansions in human cancer

Expansion of a single repetitive DNA sequence, termed a tandem repeat (TR), is known to cause more than 50 diseases. However, repeat expansions are often not explored beyond neurological and neurodegenerative disorders. In some cancers, mutations accumulate in short tracts of TRs (STRs), a phenomenon termed microsatellite instability (MSI); however larger repeat expansions have not been systematically analyzed in cancer. Here, we identified TR expansions in 2,622 cancer genomes, spanning 29 cancer types. In 7 cancer types, we found 160 recurrent repeat expansions (rREs); most of these (155/160) were subtype specific. We found that rREs were non-uniformly distributed in the genome with an enrichment near candidate cis-regulatory elements, suggesting a role in gene regulation. One rRE located near a regulatory element in the first intron of UGT2B7 was detected in 34% of renal cell carcinoma samples and was validated by long-read DNA sequencing. Moreover, targeting cells harboring this rRE with a rationally designed, sequence-specific DNA binder led to a dose-dependent decrease in cell proliferation. Overall, our results demonstrate that rREs are an important but unexplored source of genetic variation in human cancers, and we provide a comprehensive catalog for further study.

genomics↗