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

生物体对压力环境的反应因人而异，部分取决于先前对压力源的经验。这种变化使得预测一个人或一群人将如何忍受压力事件变得极其困难。从历史上看，对压力的研究侧重于压力反应，而不是反应变化的后果。该项目将采用比较的方法，将先前暴露于轻度热应激和未暴露于轻度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，开发一个模型，以预测压力事件何时对繁殖产生负面影响。此外，研究人员将研究如何将抗逆性和适应力传递给下一代。该项目将把生物学和工程学整合到阿拉巴马州学生的研究和教育活动中。首先，为了突出生物学和工程学之间的联系，该项目将在暑期课程中向高中生传授受自然启发的技术。其次，本项目将组织一个招聘会，展示理工科结合的职业，让参与者有机会结识来自不同背景的专业人士。最后，这个项目将发展一个实践工作坊，让生物学和工程学的学生学习如何将数据转化为数学模型，并积极学习功能基因组学和表观遗传学的课程。通过研究和教育将生理学、基因组学和工程学结合起来，该项目将为早期科学家提供培训、指导和培养跨学科思维的机会。当生物在发育过程中适应轻微的压力源时，整个分类群都可以增加压力恢复能力。同时，严重的压力可能会降低健康水平。这种环境依赖性使得很难预测环境的变化如何改变个体的适应结果和群体的成功。已经提出了几个理论模型来描述对应激源的反应，但仍然缺乏预测模型和可靠的应激抵抗和恢复的生物标志物。为了弥补这一差距，本项目的目标是利用材料工程中的路径分析和损伤愈合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、应力诱导的分子和细胞损伤以及健康指数联系起来。具体来说，该项目将测试持续损伤（如DNA损伤和脂质过氧化）降低生殖输出的假设，以及应激调节通过控制损伤保护、修复和去除的基因的表观遗传调节增加应激抗性的假设。本项目将利用先前建立的斑马雀（Taeniopygia guttata）热调节协议，评估1)幼鸟的轻度热调节是否开启损伤保护机制，如热休克蛋白、抗氧化剂和DNA修复，减少成年期热应激引起的损伤积累，并最大限度地减少热应激对生殖输出的负面影响；2) F1代的热调节是否会引起F2代损伤保护、修复和清除调控基因的表观遗传修饰。该项目由综合生态生理学和综合有机体系统的生理机制和生物力学项目共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.