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CAREER: Signal to Noise: How Complex Social Information Regulates Brain Genomics and Behavior

职业：信噪比：复杂的社会信息如何调节大脑基因组和行为

基本信息

批准号：
2045901
负责人：
Clare Rittschof
金额：
$ 112.39万
依托单位：
University of Kentucky Research Foundation
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2045901&HistoricalAwards=false
关键词：
CAREER Signal Noise How Complex

项目摘要

Life experiences change individual behavior through complex interactions between environmental inputs and gene activity in the brain; it is unclear why certain experiences have lasting effects on behavior while other effects are easily reversed. This question is relevant to animal biodiversity, but also human health research, where one goal is to mitigate the behavioral impacts of experiences like social trauma. Though dynamic brain gene activity underlies experience-induced changes in behavior, the exact mechanisms that regulate the persistence of an experience are unclear. For example, experience may chemically alter brain DNA and therefore permanently change gene activity. However, a change in gene activity itself may be temporary, but lead to permanent changes in other factors that influence behavior, like brain structure. This study uses experimental manipulations of gene regulating mechanisms to determine whether certain ones reliably predict the longevity of an experience. The subject of these studies is the honey bee (Apis mellifera), a critical crop pollinator with a well-established relationship between social experience, brain gene activity, and aggressive behavior. Teams composed of students and beekeepers will complete research objectives and organize a summit that introduces high school students to research results and academic, industry, and non-profit career opportunities in Agricultural STEM. In addition to filling critical knowledge gaps in the study of behavioral diversity, this project will improve public science literacy and enhance partnerships among students and professionals inside and outside of academia. These steps contribute to an overall outcome of increased STEM workforce diversity, retention and career success.In honey bees, adult defensive aggression and brain gene expression are persistently changed by social information accrued over the course of several days. To a degree, these phenotypes are also responsive to immediate information about threats to the beehive, enabling researchers to assess the circumstances under which persistent social experiences are updated by new information. Persistent effects are correlated with changes in brain DNA methylation and decreased lipid content in a peripheral endocrine tissue known to impact brain gene expression, the fat body. Thus, the longevity of social experience could be a result of the gene regulatory impacts of brain DNA methylation, endocrine signaling patterns, or both. Researchers use intricate adult social manipulations to produce bees that display similar levels of aggression, but with different gene regulatory underpinnings (variation in brain DNA methylation, fat body lipid content, or both). These bees will be used to examine which regulatory mechanisms predict the strength of response to new information, in terms of behavior, brain physiology (mitochondrial bioenergetics), and genome function (gene expression and chromatin accessibility measured using RNA-seq, bisulfite-seq and ATAC-seq). Larval bees also show persistent behavioral effects of their pre-adult environment. Manipulations of larvae and measures of adult behavior will be used to determine whether the longevity mechanisms identified in adults also apply to a second life stage. This study addresses critical knowledge gaps in the relationship between brain genomics and behavioral plasticity, including how peripheral systems and brain epigenetic mechanisms work together to regulate brain gene expression and behavior.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

生活经历通过环境输入和大脑基因活动之间复杂的相互作用改变个人行为；目前还不清楚为什么某些经历会对行为产生持久影响，而其他影响却很容易逆转。这个问题与动物生物多样性相关，也与人类健康研究相关，其中一个目标是减轻社会创伤等经历对行为的影响。尽管动态的大脑基因活动是体验引起的行为变化的基础，但调节体验持续性的确切机制尚不清楚。例如，经验可能会化学改变大脑 DNA，从而永久改变基因活动。然而，基因活动本身的变化可能是暂时的，但会导致影响行为的其他因素（例如大脑结构）发生永久性变化。这项研究利用基因调节机制的实验操作来确定某些机制是否能够可靠地预测体验的寿命。这些研究的主题是蜜蜂（Apis mellifera），它是一种重要的作物传粉媒介，在社会经验、大脑基因活动和攻击行为之间有着明确的关系。由学生和养蜂人组成的团队将完成研究目标，并组织一次峰会，向高中生介绍农业 STEM 领域的研究成果以及学术、行业和非营利职业机会。除了填补行为多样性研究中的关键知识空白之外，该项目还将提高公众科学素养，并加强学术界内外学生和专业人士之间的伙伴关系。这些步骤有助于提高 STEM 劳动力多样性、保留率和职业成功的总体结果。在蜜蜂中，成年蜜蜂的防御性攻击和大脑基因表达会因几天内积累的社会信息而持续改变。在某种程度上，这些表型也对有关蜂巢威胁的即时信息做出反应，使研究人员能够评估持久的社会经验被新信息更新的情况。持久的影响与大脑 DNA 甲基化的变化以及已知会影响大脑基因表达（脂肪体）的外周内分泌组织中脂质含量的降低有关。因此，社会经验的持久性可能是大脑 DNA 甲基化、内分泌信号模式或两者兼而有之的基因调控影响的结果。研究人员使用复杂的成年社会操纵来培育表现出相似攻击性水平的蜜蜂，但具有不同的基因调控基础（大脑 DNA 甲基化、脂肪体脂质含量的变化，或两者兼而有之）。这些蜜蜂将用于检查哪些调节机制可以预测对新信息的反应强度，包括行为、大脑生理学（线粒体生物能学）和基因组功能（使用 RNA-seq、亚硫酸氢盐-seq 和 ATAC-seq 测量的基因表达和染色质可及性）。幼蜂还表现出成虫前环境的持续行为影响。对幼虫的操作和对成虫行为的测量将用于确定在成虫中发现的长寿机制是否也适用于第二个生命阶段。这项研究解决了大脑基因组学和行为可塑性之间关系的关键知识差距，包括外围系统和大脑表观遗传机制如何协同工作来调节大脑基因表达和行为。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。