Biology subjects

Asgari, D.

Publications and source records attributed to Asgari, D..

3 recordsLinked to original sources

bioRxiv2022

Uncertainty favors an induced immune response to infection

Organisms use constitutive or induced defenses against pathogens, parasites, and herbivores. Constitutive defenses are constantly on, whereas induced defenses are activated upon exposure to an enemy. Constitutive and induced defenses each have costs and benefits, which can affect the type of defense that evolves in response to pathogens. Previous models that compared the two lacked mechanistic details about host defense, did not consider pathogen proliferation rates, or lacked both features. To address this gap, we developed a detailed mechanistic model of the well-characterized Drosophila melanogaster immune signaling network. We evaluated the factors favoring the evolution of constitutive and induced defenses by comparing the fitness of each strategy under stochastic fly-bacteria interactions. We show that an induced defense is favored when bacteria are at low density, heterogeneously distributed, or have fluctuating distributions in ways that depend on the bacterial proliferation rate. Our model also predicts that the specific negative regulators that optimize the induced response depend on the bacterial proliferation rate. We therefore conclude that an induced immune defense is favored in environments where bacterial encounters are uncertain--because of heterogeneity in spatial or temporal distributions--but that benefit depends on the mechanism of induction and pathogen properties.

evolutionary biology↗

bioRxiv2021

Induction and inhibition of Drosophila X chromosome gene expression are both impeded by the dosage compensation complex

Sex chromosomes frequently differ from the autosomes in the frequencies of genes with sexually dimorphic or tissue-specific expression. Multiple hypotheses have been put forth to explain the unique gene content of the X chromosome, including selection against male-beneficial X-linked alleles, expression limits imposed by the haploid dosage of the X in males, and interference by the dosage compensation complex (DCC) on expression in males. Here, we investigate these hypotheses by examining differential gene expression in Drosophila melanogaster following several treatments that have widespread transcriptomic effects: bacterial infection, viral infection, and abiotic stress. We found that genes that are induced (up-regulated) by these biotic and abiotic treatments are frequently under-represented on the X chromosome, but so are those that are repressed (down-regulated) following treatment. We further show that whether a gene is bound by the DCC in males can largely explain the paucity of both up- and down-regulated genes on the X chromosome. Specifically, genes that are bound by the DCC, or close to a DCC high-affinity site, are unlikely to be up- or down-regulated after treatment. This relationship, however, could partially be explained by a correlation between differential expression and breadth of expression across tissues. Nonetheless, our results suggest that DCC binding, or the associated chromatin modifications, inhibit both up- and down-regulation of X chromosome gene expression within specific contexts. We propose multiple possible mechanisms of action for the effect, including a role of Males absent on the first (Mof), a component of the DCC, as a dampener of gene expression variance in both males and females. This effect could explain why the Drosophila X chromosome is depauperate in genes with tissue-specific or induced expression, while the mammalian X has an excess of genes with tissue-specific expression.

genomics↗

bioRxiv2021

Gene expression in Lucilia sericata (Diptera: Calliphoridae) larvae exposed to Pseudomonas aeruginosa and Acinetobacter baumanii identifies shared and microbe-specific induction of immune genes

Antibiotic resistance is a continuing challenge in medicine. There are various strategies for expanding antibiotic therapeutic repertoires, including the use of blow flies. Their larvae exhibit strong antibiotic and antibiofilm properties that alter microbiome communities. One species, Lucilia sericata, is used to treat problematic wounds due to its debridement capabilities and its excretions and secretions that kill some pathogenic bacteria. There is much to be learned about how L. sericata interacts with microbiomes at the molecular level. To address this deficiency, gene expression was assessed after feeding exposure (1 hour or 4 hours) to two clinically problematic pathogens: Pseudomonas aeruginosa and Acinetobacter baumanii. The results identified immunity related genes that were differentially expressed when exposed to these pathogens, as well as non-immune genes possibly involved in gut responses to bacterial infection. There was a greater response to P. aeruginosa that increased over time, while few genes responded to A. baumanii exposure and expression was not time-dependent. The response to feeding on pathogens indicates a few common responses and features distinct to each pathogen, which is useful in improving wound debridement therapy and helps develop biomimetic alternatives.

immunology↗