Genetic basis of diet-dependent responses across the lifespan

整个生命周期饮食依赖性反应的遗传基础

基本信息

批准号：
10535264
负责人：
Nicole Lynn Stuhr
金额：
$ 4.68万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-11 至 2023-08-10
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10535264
关键词：
Ablation Address Aging Bacteria Bacteroidetes Behavior Behavioral Biological Assay Caenorhabditis elegans Choice Behavior Complex Computational Biology Consumption Decision Making Development Diet Dietary History Disease Eating Energy Intake Environment Escherichia coli Ethyl Methanesulfonate Excision Exposure to Food Food Contamination Foundations Future Genetic Genomics Goals Health Human Knowledge Laboratories Lead Longevity Maintenance Mediating Metabolic Methylobacterium Modeling Modification Molecular Biology Mutation Nervous system structure Neurobiology Neurons Nutraceutical Olfactory Pathways Organism Paper Pathway interactions Phenotype Physiological Physiology Proteobacteria Publishing Research Shapes Signal Pathway Societies Source Sphingomonas Standardization Training Variant Xanthomonas base combat dietary dietary control experience good diet head-to-head comparison healthspan healthy aging holistic approach insight life history mutant neural circuit novel nutritional genomics phrases preference response sensory integration species difference trait transcriptomics

项目摘要

Project Summary: C. elegans respond to changes in food availability, environmental conditions, and bacterial diets through nervous system integration of sensory information and coordinated behavioral, physiological, and metabolic responses12, 13, 14. The laboratory and natural environments of C. elegans differ drastically in the bacterium present – the laboratory environment relies on monocultures of E. coli, while the natural environment exposes C. elegans to a wide variety of bacterial species including Bacteroidetes, Proteobacteria, and Actinobacteria1, 2. My recently published study takes advantage of bacterial diets found in both C. elegans natural and laboratory environments and provides a comprehensive assessment of changes in physiology and transcriptomic signatures as a result to simply changing the bacteria diet worms were propagated on3. To my knowledge, this paper was the first head-to-head comparison demonstrating how the natural environment controls physiology incongruously to that of the laboratory environment, however, I realized that this study is just the beginning of understanding the multiplexed relationship between dietary exposure and life history traits. The overarching goal of this proposal is to reveal novel mechanisms of the complex food-based decision making to elucidate the underlying genetic basis of diet-dependent responses across the lifespan. With two main approaches, I plan to take advantage of the amenable C. elegans model and examine how two distinct physiological attributes, development and food choice, can be differentially impacted by dietary exposure to lifespan-promoting bacteria. The first aim will be to identify the neurocircuitry involved in deciding between two bacterial diets by developing unbiased food choice assays (1a). With the use of these assays, I plan to identify the olfactory pathways involved with a combination of neuronal ablation and genetic mutants (1b). Finally, I will examine how these mutations in the olfactory pathways will influence C. elegans adaptive capacity and the multiple aspects of physiology that converge upon aging and lifespan (1c). My second aim relies on genetics to examine how bacterial diet controls normal progression of development. I plan to approach this aim by identifying developmentally slow mutants generated by an ethyl methanesulfonate screen in order to reveal novel genetic regulators of developmental timing (2a). Due to the high conservation of signaling pathways involved in dietary response, these studies will reveal new insights into impacts diet has on health on longevity and stimulate future studies to use food as a nutraceutical to combat the onset of aging and diseases.

项目概要：线虫通过神经系统对食物供应、环境条件和细菌饮食的变化做出反应感觉信息和协调的行为、生理和代谢反应的系统整合12， 13, 14. 线虫的实验室环境和自然环境在存在的细菌方面存在显着差异 - 实验室环境依赖于大肠杆菌的单一培养，而自然环境则将秀丽隐杆线虫暴露于多种细菌种类，包括拟杆菌门、变形菌门和放线菌门1、2。我最近发表的研究利用了秀丽隐杆线虫自然和实验室环境中发现的细菌饮食并对由此产生的生理学和转录组特征的变化进行全面评估据我所知，这篇论文是第一篇。头对头的比较展示了自然环境如何与此不一致地控制生理机能然而，我意识到这项研究只是了解实验室环境的开始饮食暴露与生活史特征之间的多重关系该提案的总体目标是。揭示复杂的基于食物的决策的新机制，以阐明潜在的遗传基础我计划利用两种主要方法来研究整个生命周期的饮食依赖性反应。顺从的秀丽隐杆线虫模型并检查两种不同的生理属性（发育和食物）如何饮食中暴露于促进寿命的细菌会对选择产生不同的影响。通过发展公正的食物选择来识别参与决定两种细菌饮食的神经回路通过使用这些测定，我计划确定与组合相关的嗅觉通路。最后，我将研究这些突变如何影响嗅觉。途径将影响线虫的适应能力和生理学的多个方面我的第二个目标依赖于遗传学来研究细菌饮食如何控制正常。我计划通过识别产生的发育缓慢的突变体来实现这一目标。通过甲磺酸乙酯筛选，以揭示发育时间的新型遗传调节因子 (2a)。由于饮食反应中涉及的信号通路高度保守，这些研究将揭示新的深入了解饮食对健康和长寿的影响，并刺激未来的研究将食物用作营养保健品对抗衰老和疾病的发生。