Biology subjects

McCartney, B. M.

Publications and source records attributed to McCartney, B. M..

4 recordsLinked to original sources

bioRxiv2020

Arc1 modulates microbiota-responsive developmental and metabolic traits in Drosophila

Perturbations to animal-associated microbial communities (the microbiota) have deleterious effects on various aspects of host fitness, but the molecular processes underlying these impacts are poorly understood. Here we identify a novel connection between the microbiota and the neuronal factor Arc1 that affects growth and metabolism in Drosophila. We find that Arc1 exhibits tissue-specific microbiota-dependent expression changes, and that germ-free flies bearing a null mutation of Arc1 exhibit delayed and stunted larval growth, along with a variety of molecular, cellular, and organismal traits indicative of metabolic dysregulation. Remarkably, we show that the majority of these phenotypes can be fully suppressed by mono-association with a single Acetobacter sp. isolate, through mechanisms involving both bacterial diet modification and live bacteria. Additionally, we provide evidence that Arc1 function in key neuroendocrine cells of the larval brain modulates growth and metabolic homeostasis under germ-free conditions. Our results reveal a novel role for Arc1 in modulating physiological responses to the microbial environment, and highlight how host-microbe interactions can profoundly impact the phenotypic consequences of genetic mutations in an animal host. SUMMARYDrosophila Arc1 exhibits microbiota-dependent, tissue-specific differential expression and functionally interacts with a key Acetobacter sp. isolate to regulate developmental growth and metabolic traits.

physiology↗

bioRxiv2020

Fibronectin-Based Nanomechanical Biosensors to Map 3D Strains in Live Cells and Tissues

Mechanical forces are integral to a wide range of cellular processes including migration, differentiation and tissue morphogenesis; however, it has proved challenging to directly measure strain at high spatial resolution and with minimal tissue perturbation. Here, we fabricated, calibrated, and tested a fibronectin (FN)-based nanomechanical biosensor (NMBS) that can be applied to cells and tissues to measure the magnitude, direction, and dynamics of strain from subcellular to tissue length-scales. The NMBS is a fluorescently-labeled, ultrathin square lattice FN mesh with spatial resolution tailored by adjusting the width and spacing of the lattice fibers from 2-100 {micro}m. Time-lapse 3D confocal imaging of the NMBS demonstrated strain tracking in 2D and 3D following mechanical deformation of known materials and was validated with finite element modeling. Imaging and 3D analysis of the NMBS applied to single cells, cell monolayers, and Drosophila ovarioles demonstrated the ability to dynamically track microscopic tensile and compressive strains in various biological applications with minimal tissue perturbation. This fabrication and analysis platform serves as a novel tool for studying cells, tissues, and more complex systems where forces guide structure and function.

bioengineering↗

bioRxiv2019

Identification of Microbiota-Induced Gene Expression Changes in the Drosophila melanogaster Head

Symbiotic microorganisms exert multifaceted impacts on the physiology of their animal hosts. Recent discoveries have shown the gut microbiota influence host brain function and behavior, but the host and microbial molecular factors required to actuate these effects are largely unknown. To uncover molecular mechanisms that underlie the gut-microbiota-brain axis, we used Drosophila melanogaster and its bacterial microbiota as a model to identify microbiota-dependent gene expression changes in the host brain and head. Specifically, we employed RNA-seq and nanoString nCounter technology to identify Drosophila genes that exhibit altered transcript levels in fly heads upon elimination of the microbiota. The identified genes, some of which exhibited sex-specific differences, have demonstrated or inferred functional roles in the immune response, metabolism, neuronal activity, and stress resistance. Overall, this study reveals microbiota-responsive genes in the fly head, an anatomical structure not previously investigated in this context. Our results serve as a foundation for future investigations of how microbe-driven gene expression changes impact Drosophila biology.

microbiology↗

bioRxiv2018

Microbiota-dependent elevation of Alcohol Dehydrogenase in Drosophila is associated with changes in alcohol-induced hyperactivity and alcohol preference

The gut microbiota impacts diverse aspects of host biology including metabolism, immunity, and behavior, but the scope of those effects and their underlying molecular mechanisms are poorly understood. To address these gaps, we used Two-dimensional Difference Gel Electrophoresis (2D-DIGE) to identify proteomic differences in male and female Drosophila heads raised with a conventional microbiota and those raised in a sterile environment (axenic). We discovered 22 microbiota-dependent protein differences, and identified a specific elevation in Alcohol Dehydrogenase (ADH) in axenic male flies. Because ADH is a key enzyme in alcohol metabolism, we asked whether physiological and behavioral responses to alcohol were altered in axenic males. Here we show that alcohol induced hyperactivity, the first response to alcohol exposure, is significantly increased in axenic males, requires ADH activity, and is modified by genetic background. While ADH activity is required, we did not detect significant microbe-dependent differences in systemic ADH activity or ethanol level. Like other animals, Drosophila exhibit a preference for ethanol consumption, and here we show significant microbiota-dependent differences in ethanol preference specifically in males. This work demonstrates that male Drosophilas association with their microbiota affects their physiological and behavioral responses to ethanol.

microbiology↗