Biology subjects

Chen, T. Y.

Publications and source records attributed to Chen, T. Y..

3 recordsLinked to original sources

bioRxiv2025

Magnetosome organelles are organized through interactions between McaA and McaB that alter the dynamics of the bacterial actin-like protein MamK

Magnetotactic bacteria (MTB) are a group of Gram-negative species that produce a lipid-bounded organelle, the magnetosome, in which a magnetic crystal is biomineralized. MTB use magnetosomes to align with the geomagnetic field for improved navigation of their environment. To optimize this alignment, these species organize their magnetosomes in a linear fashion using a handful of factors including the bacterial actin-like protein MamK. Despite these shared features, there is a broad diversity of species-specific linear magnetosome chain arrangements within MTB, but the molecular mechanisms behind these phenotypic variations are unclear. Recently, genetic analyses showed that two proteins McaA and McaB interface with the chain organization machinery of Magnetospirillum magneticum AMB-to arrange magnetite crystals in a series of subchains rather than the single cohesive chains found in closely related MTB. Here, we use in vivo co-immunoprecipitation in AMB-1 to demonstrate protein-protein interactions between McaA, McaB, and MamK. Experiments with McaA truncation mutants and conditional control of McaB localization determined that McaA-McaB interactions are dependent on amino acids 530-665 of McaA and McaB localization to the magnetosome chain. We further show that disrupting the McaA-McaB interaction alters the spatial dynamics of MamK in vivo We present a model in which protein-protein interactions between McaA, McaB, and MamK drive changes in MamK behavior to establish AMB-1s magnetosome chain organization. IMPORTANCEMagnetosomes model for understanding the cell biology of bacterial organelles and the mechanisms of bacterial cell organization. MamK, one of the best-studied bacterial actins, is a notable player in magnetosome chain assembly. This work explores how MamK dynamics are altered by two potential bacterial actin binding proteins, McaA and McaB. This system illustrates how changes in bacterial cytoskeleton regulation result in different organization of subcellular compartments. The conclusions from this research also have implications for understanding the broader evolutionary strategies for regulation of actin-like proteins and compartment organization diversification in bacteria.

microbiology↗

bioRxiv2024

Requirement for Fc effector function is overcome by binding potency for broadly reactive anti-alphavirus antibodies

Alphaviruses are emerging public health threats. Broadly reactive anti-alphavirus monoclonal antibodies (mAbs) have been shown to be protective in mouse models of infection. However, the mechanism of Fc-dependent or Fc-independent heterologous protection remains ill-defined in vivo. Here, we used two vaccine-elicited, broadly reactive, anti-alphavirus mAbs, SKT05 and SKT20, to establish correlates of mAb-mediated protection during Venezuelan equine encephalitis virus (VEEV) challenge. SKT20 required Fc effector functions to prevent lethality. In contrast, SKT05-mediated survival was independent of Fc effector functions, which is likely linked to early viral control through potent egress inhibition. However, control of virus replication and spread with SKT05 was Fc-dependent; these findings extended to additional in vivo models with alternative VEEV subtypes and chikungunya virus. During therapeutic delivery of SKT05, Fc effector functions were only required at 3 days post-infection. The necessity of Fc effector functions for SKT20 was related to mAb binding avidity rather than epitope and could be overcome by increasing the dose of SKT20 relative to the functional avidity of SKT05. Collectively, this study identified antibody avidity as a correlate for in vivo efficacy and associated Fc-dependent mechanisms that can be leveraged for therapeutic development of monoclonal antibodies against alphaviruses. One sentence summaryFunctional avidity of broadly reactive anti-alphavirus antibodies dictates requirement for Fc-mediated protection.

microbiology↗

bioRxiv2020

Bitbow: a digital format of Brainbow enables highly efficient neuronal lineage tracing and morphology reconstruction in single brains

Identifying the cellular origins and mapping the dendritic and axonal arbors of neurons have been century old quests to understand the heterogeneity among these brain cells. Classical chemical and genetic methods take advantage of light microscopy and sparse labeling to unambiguously, albeit inefficiently, trace a few neuronal lineages or reconstruct their morphologies in each sampled brain. To improve the analysis throughput, we designed Bitbow, a digital format of Brainbow which exponentially expands the color palette to provide tens of thousands of spectrally resolved unique labels. We generated transgenic Bitbow Drosophila lines, established statistical tools, and streamlined sample preparation, image processing and data analysis pipelines to allow conveniently mapping neural lineages, studying neuronal morphology and revealing neural network patterns with an unprecedented speed, scale and resolution.

neuroscience↗