Integrating engineering theory and biological measures to model stress resilience, damage, and fitness-related consequences

整合工程理论和生物测量来模拟压力恢复、损伤和健康相关后果

• 批准号: 2015802
• 负责人: Haruka Wada
• 金额: $ 196.19万
• 依托单位: Auburn University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2015802&HistoricalAwards=false
• 关键词: Integrating; engineering; theory; biological; measures

How organisms respond to a stressful situation varies greatly among individuals and partly depends on prior experience with the stressor. This variation makes predictions of how an individual or population of individuals will endure stressful events extremely difficult. Historically, studies on stress focused on stress responses rather than the consequences of variation in responses. Using a comparative approach with individual birds that have had prior exposure to mild heat stress, and those that have not, this project will integrate biology and engineering approaches to develop a model to predict when stressful events negatively impact reproduction. Further, the investigators will examine how stress resistance and resilience can be transmitted to the next generation. This project will integrate biology and engineering in research and educational activities for students in Alabama. First, to highlight the connection between biology and engineering, the project will teach high school students about technologies inspired by nature in a summer program. Second, this project will organize a career fair, showcasing careers that integrate science and engineering degrees and giving opportunities for the participants to meet professionals from diverse backgrounds. Finally, this project will develop a hands-on workshop where students in biology and engineering learn how to turn data into mathematical models and active learning courses on functional genomics and epigenetics. By incorporating physiology, genomics, and engineering through research and education, the project will provide training, mentorship, and opportunities to nurture interdisciplinary mindset in early-stage scientists. Organisms across taxa can increase stress resilience when conditioned to a mild stressor during development. At the same time, severe levels of stress may decrease fitness. This context-dependency makes it difficult to predict how a shift in an environment alters the fitness outcome of an individual and success of a population. Several theoretical models have been put forth to characterize responses to a stressor, yet predictive models and reliable biomarkers of stress resistance and resilience are still lacking. To bridge this gap, the goal of this project is to utilize path analysis and Damage-Healing Mechanics from material engineering to develop mechanistic and predictive mathematical models, linking developmental and adult environments, epigenetic modifications, stress-induced molecular and cellular damage, and fitness indices. Specifically, this project will test the hypotheses that persistent damage, such as DNA damage and lipid peroxidation, lowers reproductive output and that stress conditioning increases stress resistance through epigenetic regulation of genes controlling damage protection, repair, and removal. Using a previously established protocol of heat conditioning in zebra finches (Taeniopygia guttata), the present project will assess 1) whether mild heat conditioning in juveniles turns on damage protective mechanisms such as heat shock proteins, antioxidants, and DNA repair, reduces accumulation of damage induced by heat stress in adulthood, and minimizes the negative effects of heat stress on reproductive output, and 2) whether heat conditioning in the F1 generation causes epigenetic modification of genes regulating damage protection, repair, and removal in the F2 generation.This project was co-funded by the Integrative Ecological Physiology and the Physiological Mechanisms and Biomechanics programs in Integrative Organismal Systems.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.

生物体对压力环境的反应因人而异，在一定程度上取决于先前对应激源的经验。这种变化使得预测一个人或一群人将如何承受压力事件变得极其困难。从历史上看，关于压力的研究集中在压力反应上，而不是反应变化的后果上。这个项目通过对之前有过轻度热应激的鸟类和没有经历过轻微热应激的鸟类个体进行比较，将生物学和工程学方法结合起来，开发出一个模型来预测应激事件何时会对繁殖产生负面影响。此外，研究人员将研究抗压性和韧性如何传递给下一代。该项目将在阿拉巴马州的学生的研究和教育活动中整合生物学和工程学。首先，为了突出生物学和工程学之间的联系，该项目将在暑期项目中向高中生传授受自然启发的技术。其次，该项目将组织一场招聘会，展示融合了科学和工程学位的职业，并为参与者提供机会认识来自不同背景的专业人士。最后，该项目将开发一个动手工作坊，生物和工程专业的学生将在其中学习如何将数据转化为数学模型，以及关于功能基因组学和表观遗传学的积极学习课程。通过研究和教育将生理学、基因组学和工程学结合在一起，该项目将提供培训、指导和机会，以培养早期科学家的跨学科思维。在发育过程中，当适应温和的应激源时，不同类群的有机体可以提高应激韧性。与此同时，严重的压力水平可能会降低健康水平。这种对环境的依赖使得很难预测环境的变化如何改变个人的健康结果和群体的成功。已经提出了几个理论模型来表征对应激源的反应，但仍然缺乏预测模型和可靠的抗逆性和恢复力生物标志物。为了弥合这一差距，该项目的目标是利用材料工程学的路径分析和损伤修复力学来开发机械和预测数学模型，将发育和成人环境、表观遗传修饰、应激诱导的分子和细胞损伤以及健康指数联系起来。具体地说，这个项目将测试这样的假设，即持续损伤，如DNA损伤和脂质过氧化，降低生殖产量，以及应激条件通过控制损伤保护、修复和移除的基因的表观遗传调节来增强抗逆性。利用先前在斑马雀(Taeniopygia Guttata)中建立的热调节方案，本项目将评估1)幼年的温和热调节是否开启了损伤保护机制，如热休克蛋白、抗氧化剂和DNA修复，减少了成年后热应激导致的损伤积累，并将热应激对生殖输出的负面影响降至最低；2)F1代的热调节是否导致调节损伤保护、修复、这个项目是由综合生态生理学和综合组织系统中的生理机制和生物力学项目共同资助的。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。