Molecular mechanisms underlying microbial modulation of host behavior

行为生物学的一个中心问题是环境和遗传因素如何塑造行为特征， 允许充分的个性。稳态行为，如喂养和食物偏好是主要的 遗传倾向与食物环境相互作用，产生不同的饮食习惯的例子。 然而，这些程序被宿主相关的微生物进一步修改，表明整个系统 控制行为表型远比最初预期的复杂。仍然存在的关键问题 要解决的问题是：在何种程度上做宿主微生物的相互作用有助于行为的个体差异？ 具体来说，在宿主-微生物共生的背景下，行为的基因调控是如何运作的？中隐含 这个问题是宿主-微生物共生的扰动导致异常行为的假设。 在某些个人或人群中，这是一个对人类健康至关重要但尚未解决的问题。 我的研究项目的目标是确定宿主-微生物相互作用如何塑造行为。 我的实验室研究黑腹果蝇的觅食和食物选择行为， 我开发的可以精确配置苍蝇微生物群的技术。我假设进食行为和 食物偏好是宿主遗传-微生物组相互作用的产物，这在一定程度上决定了 个人的长期健康。我们最近的数据表明，觅食和饮食选择的偏好不同， 微生物组，改变微生物组触发果蝇内特定细胞簇的转录变化 大脑，涉及预测影响行为的基因。在这个五年计划中，我将利用苍蝇遗传学和国家- 最先进的基因组学和代谢组学工具，以确定基因调控网络和机制 潜在的微生物调节宿主行为。预期结果包括全面的肠道内分泌 单细胞转录组尺度和代谢物基因的信号传导和器官间通讯图 互动网络。微生物组响应基因、神经肽和代谢物对 宿主的进食行为和食物偏好将被揭示。由于我们对这些因素的相互作用知之甚少， 宿主遗传学和微生物组有助于复杂的行为，我的研究有可能取得进展 行为遗传学的基础知识，也可以识别可能起作用的基因或过程， 类似地，在果蝇和哺乳动物中作为治疗行为障碍如进食障碍和肥胖症的靶标。

A central question in behavioral biology is how environmental and genetic factors shape behavioral traits, allowing for substantial individuality. Homeostatic behaviors like feeding and food preferences are prime examples of genetic predispositions interacting with the food environment to produce diverse feeding habits. However, these programs are further modified by host-associated microbes, suggesting the overall systems controlling behavioral phenotype is far more complex than first anticipated. The critical questions that remain to be addressed are: to what extent do host-microbe interactions contribute to individual differences in behavior? Specifically, how does gene regulation of behavior operate in the context of host-microbe symbiosis? Implicit in this question is the hypothesis that perturbation of host-microbe symbiosis results in aberrant behavioral outcomes in certain individuals or populations, a topic fundamental to human health yet unsolved. The goal of my research program is to define how behaviors are shaped by host-microbe interactions. My lab studies foraging and food choice behaviors in the fly Drosophila melanogaster, using a gnotobiotic system I developed that permits precise configuration of the fly microbiome. I hypothesize that feeding behavior and food preferences are the product of host genetics-microbiome interactions, which determine, in part, an individual’s long-term health. Our recent data show that foraging and diet selection preferences vary by the microbiome, and altering the microbiome triggers transcriptional changes in specific cell clusters within the fly brain, involving genes predicted to affect behavior. In this five-year plan, I will leverage fly genetics and state- of-the-art genomics and metabolomics tools to identify the gene regulatory networks and mechanisms underlying microbial modulation of host behavior. Expected outcomes include comprehensive gut endocrine signaling and inter-organ communication maps at single-cell transcriptome scale and metabolite-gene interactions networks. The causal effects of microbiome-responsive genes, neuropeptides, and metabolites on host feeding behavior and food preferences will be revealed. Since we know little about how the interplay of host genetics and microbiome contribute to complex behavior, my research has the potential to advance fundamental knowledge in behavioral genetics but also to identify genes or processes that may function similarly in Drosophila and mammals as targets to treat behavioral disorders, such as eating disorders and obesity.