DISSERTATION RESEARCH: Energetic mechanisms underlying fitness consequences of immune responses

论文研究：免疫反应适应性后果背后的能量机制

• 批准号: 1701876
• 负责人: Kristi Montooth
• 金额: $ 1.99万
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1701876&HistoricalAwards=false
• 关键词: DISSERTATION; RESEARCH; Energetic; mechanisms; underlying

This research tests the hypothesis that individuals with inefficient energy metabolism will have a decreased ability to fight infection, which in turn will decrease their future reproductive ability. Fighting infection requires individuals to invest energy in immune responses. These responses can deplete energy supplies that would otherwise be used for growth, maintenance, and reproduction, particularly when energy is limited. Individual organisms may be energy limited when nutrients are not available or when their genes do not allow efficient processing of nutrients into energy supplies. The research will also address questions about how fighting infection changes metabolic rate. By using the model genetic organism, Drosophila melanogaster, which has natural immune responses that are similar to humans, this project will generate critical information on how genetic variation in energy metabolism affects the ability of human cells to fight infection. This research will also be used to design new exercises for introductory biology laboratories that will help students synthesize information across diverse topics covered in introductory biology courses, from evolution to immunity and physiology.This project tests the prediction that the energy required to activate the immune system during development decreases the ability of individuals with inefficient energy metabolism to fight infection, and creating a resulting decrease in future adult reproduction. The project connects the effects of interactions between innate immunity and energy metabolism pathways at the organismal, molecular, and physiological levels in a well-studied genetic system. The experiments take advantage of a well-characterized set of genotypes, one of which has a disrupted mitochondrial-nuclear interaction that results in inefficient energy metabolism. Objective 1 will quantify whether flies with inefficient energy metabolism have lower infection survival and greater deleterious consequences for reproductive fitness after infection by a natural pathogen, Providencia rettgeri. Experiments will also modify the nutrient diet to further decrease the energy available for immune responses in all genotypes. Objective 2 will measure the activation of underlying molecular pathways and aspects of cellular energy metabolism to explain effects on tradeoffs between immunity and reproduction. Experiments include quantifying levels of antimicrobial peptide induction, measuring the amounts of key proteins in energy-sensing pathways, assessing the bacterial load during infection, and monitoring indicators of the cellular energetic state and organismal metabolic rate during infection.

这项研究检验了这样的假设，即能量代谢效率低下的个体将具有降低感染能力的能力，进而将降低其未来的生殖能力。战斗感染要求个人投资于免疫反应。这些反应会耗尽原本用于生长，维护和繁殖的能源供应，尤其是在能源有限的情况下。当营养不可用时，或者它们的基因不允许有效地将养分加工成能量供应时，单个生物可能会受到限制。该研究还将解决有关战斗感染如何改变代谢率的问题。通过使用模型的遗传生物，具有与人类相似的自然免疫反应的果蝇Melanogaster将产生有关能量代谢中遗传变异如何影响人类细胞对抗感染的能力的关键信息。这项研究还将用于设计入门生物学实验室的新练习，这些练习将帮助学生综合入门生物学课程中涵盖的各种主题的信息，从进化到免疫和生理学。这项项目测试了这一预测，即在发育过程中激活免疫系统所需的能力可以减少成人无效的成年人的能力，从而降低了成人效应的能力。该项目将天生免疫力与能量代谢途径之间的相互作用联系起来，在良好的遗传系统中，生物体，分子和生理水平之间的相互作用。该实验利用了一组良好的基因型，其中一种具有破坏的线粒体 - 核相互作用，从而导致能量代谢效率低下。目标1将量化无效能量代谢的苍蝇是否具有较低的感染存活率，并且对自然病原体Providencia rettgeri感染后生殖适应性的有害后果更大。实验还将改变营养饮食，以进一步降低所有基因型中免疫反应的能量。目标2将衡量潜在的分子途径的激活和细胞能代谢的各个方面，以解释对免疫和繁殖之间的权衡的影响。实验包括量化抗菌肽诱导水平，测量能量感应途径中关键蛋白的量，评估感染过程中细菌载荷以及监测细胞能量状态的指标和感染期间的生物代谢率。