Genomic analysis of feeding behavior and fitness in Drosophila

果蝇摄食行为和适应性的基因组分析

基本信息

批准号：
8450772
负责人：
Manyuan LONG
金额：
$ 38.66万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8450772
关键词：
Address Affect Africa African Animal Model Behavior Behavioral Behavioral Assay Behavioral Genetics Biological Assay Biological Models Biological Neural Networks Circadian Rhythms Collaborations Decision Making Development Drosophila genus Eating Ecology Environment Evolution Feeding behaviors Food Gene Mutation Genes Genetic Genetic Screening Genetic Variation Genomics Goals Homeostasis Hunger Individual Leadership Life Mammals Maps Measures Mediating Memory Molecular Molecular Genetics Mus National Institute of General Medical Sciences Neurosciences Research Obesity Pathway interactions Phenotype Physical activity Population Probability Process Publishing Quantitative Trait Loci RNA Interference Recombinant Inbred Strain Research Research Personnel Resources Rewards Risk Scientist Transgenic Organisms Variant Work base clinically relevant cost design driving force fitness fly gene discovery neuroeconomics novel therapeutic target tool

项目摘要

DESCRIPTION (provided by applicant): Although energy homeostasis is central in feeding behavior, the decision to eat is not merely a question of hunger. In a natural environment in which food is often scarce, evaluating the benefit of gaining food over the energy cost or risk in seeking and acquiring food, and the decision to either seek food or stay put and conserve energy is essential for survival. However, the genetic and molecular basis of food-seeking decision-making behaviors, and their functional significance in fitness are poorly understood. We propose a bottom-up approach: starting from well-defined behaviors that are essential for food-seeking decision-making in Drosophila, taking advantage of its rich genetic tools and genomic resources. Moreover, flies are ideal for viability studies to examine the relations between genetic variations, differences in decision- making and differences in fitness under different environmental conditions. We have already taken the critical step and designed novel assays. We will optimize the following assays for quantitative analysis in this application. Decision-making in choosing between 1) small free reward or large reward that requires work; 2) small reward or large reward with a relatively low probability in its availability; 3) small reward or large reward that is paired with potential risks of getting noxious food; and 4) immediate small reward or delayed large reward. We will take advantage of natural variation in genetics and behaviors between different D. melanogaster populations living in African. We will establish 200 recombinant inbred strains derived from original African strains with extreme behavioral phenotypes for each decision-making behavior. We will perform QTL mapping and identify QTLs that contribute to the variations in food-seeking decision-making and fitness. We will then use RNAi transgenic lines to identify specific genes and variants responsible for the above behavioral variations. Although the most likely immediate clinical relevance of our study is obesity, it will have a much broader impact on neuroeconomics, the genetic basis of behavior in general, evolution and ecology.

描述（由申请人提供）：尽管能量稳态在喂养行为中是核心，但食物的决定不仅是饥饿的问题。在粮食经常稀缺的自然环境中，评估获得食物而不是能源成本或寻求食物的风险的好处，并且决定寻求食物或保持食物或保存和节省能源对于生存至关重要。但是，对寻求食物的决策行为的遗传和分子基础及其在适应性方面的功能意义知之甚少。我们提出了一种自下而上的方法：从定义明确的行为开始，这些行为对果蝇的寻求决策至关重要，利用其丰富的遗传工具和基因组资源。此外，苍蝇是生存力研究的理想选择，以检查遗传变异，决策差异和在不同环境条件下适应性差异之间的关系。我们已经采取了关键步骤并设计了新颖的测定法。在本应用程序中，我们将优化以下测定法进行定量分析。选择1）需要工作的小奖励或大奖励的决策； 2）小奖励或大奖励，其可用性的可能性相对较低； 3）与获取有害食物的潜在风险相结合的小奖励或大奖励； 4）立即获得小奖励或延迟大奖。我们将利用居住在非洲人的不同D. melanogaster种群之间的遗传学和行为的自然变化。我们将建立200种重组近交菌株，这些近交菌株来自原始的非洲菌株，具有极端的行为表型，用于每种决策行为。我们将执行QTL映射，并识别QTL，这些QTL有助于寻求食物的决策和健身。然后，我们将使用RNAi转基因线来识别负责上述行为变化的特定基因和变体。尽管我们研究最有可能立即临床相关性是肥胖症，但它将对神经经济学（一般行为，进化和生态学的遗传基础）产生更广泛的影响。