Collaborative Research: IntBIO: The Evolution of Immune Investment Strategies Across Amphibian Ontogeny

合作研究：IntBIO：跨两栖动物个体发育的免疫投资策略的演变

• 批准号: 2316470
• 负责人: Jacques Robert
• 金额: $ 61.37万
• 依托单位: University of Rochester
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2316470&HistoricalAwards=false
• 关键词: Collaborative; Research; IntBIO; Evolution; Immune; Collaborative; Research; IntBIO; Evolution; Immune

The increasing frequency of emerging infectious diseases in humans and animals underscores the need to better understand the immune defenses that organisms deploy to ward off these infections. Notably, the ability of the immune system to fight infection changes as an organism progresses from birth to old age. After all, the risk of encountering pathogens is tied to age-related behaviors and environmental setting, and overly strong immune responses can drain precious energy and fuel autoimmune diseases. As a result, organisms of different ages may derive uneven benefits from the same types of immune responses. Building on the observation that frog (Xenopus laevis) tadpoles contain a less diverse set of adaptive T cells than those of adult frogs and instead rely more on innate-like T cells, the purpose of this project is to investigate the ecological and evolutionary factors that influence changes in T cell immunity as an organism proceeds from younger to older stages of its life. To accomplish this, the project will integrate approaches from the fields of immunology, evolutionary biology and mathematics to investigate T cell receptor diversity across amphibian species currently under existential threat worldwide from a deadly fungal pathogen. The project will provide training to a diverse group of early career scientists and spur the development of active learning modules to educate students about the immune system through the lens of frog biology. Frogs represent an optimal system to investigate age-structured investment in innate-like and adaptive T cells because of their high diversity in life histories and susceptibility to emergent pathogens. The three project objectives are to: (1) use mathematical models and empirical data to predict when evolutionary history, pathogens, and environment favor T cell diversity within and among life stages on ecological and evolutionary time scales, (2) use RACE-PCR and RNA-seq to quantify T cell receptor diversity for multiple frog species spanning the frog tree of life and known tadpole development times, and (3) experimentally manipulate early-life diet and environment in a laboratory setting to quantify the extent of developmental plasticity on frog T cell receptor diversity and infection outcomes. This proposal integrates classic immunological techniques with evolutionary genetics, mathematical modeling, lab experimentation, and natural population sampling to yield unprecedented insights into the factors that drive the evolution of immune system maturation, plasticity, and diversity. At the same time, this project will train young scientists in interdisciplinary immunology, thus contributing to the formation of the next generation of scientists with interest in immune responses.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.

人类和动物中新兴的传染病的频率日益增加，这强调了有机体部署以抵制这些感染的免疫防御措施的必要性。值得注意的是，随着生物体从出生到老年，免疫系统对抗感染的能力发生变化。毕竟，遇到病原体的风险与与年龄有关的行为和环境环境息息相关，并且过度强大的免疫反应会浪费宝贵的能量和燃料自身免疫性疾病。结果，不同年龄的生物可能会从相同类型的免疫反应中获得不均匀的好处。基于观察到青蛙（Xenopus laevis）t的t含量比成年青蛙的自适应T细胞少，而更多地依赖于天生的T细胞，该项目的目的是研究生态和进化因素，这些因素会影响T细胞免疫的变化，因为随着生物体从年轻阶段到较旧阶段，其生物会导致T细胞的变化。为此，该项目将整合来自免疫学，进化生物学和数学领域的方法，以研究目前来自致命的真菌病原体世界上存在的威胁的两栖动物的T细胞受体多样性。该项目将为各种各样的早期职业科学家提供培训，并刺激积极学习模块的发展，以通过青蛙生物学的镜头对学生进行有关免疫系统的教育。青蛙代表了一个最佳系统，用于研究对先天性和适应性T细胞的年龄结构投资，因为它们的生活历史多样性和对新兴病原体的易感性。这三个项目目标是：（1）使用数学模型和经验数据来预测何时进化历史，病原体和环境何时在生态和进化时间尺度内和生命阶段内部和之间的T细胞多样性，（（2）使用种族-PCR和RNA-SEQ将T细胞受体多样性量化为跨越生命和已知饮食的frog frog tripertip and Weartip and tripertip and tripertip and Tripertim and Weartization Time and time time Time（3）一种实验室环境，可量化青蛙T细胞受体多样性和感染结果的发育可塑性程度。该建议将经典的免疫技术与进化遗传学，数学建模，实验室实验和自然种群抽样相结合，以产生对推动免疫系统成熟，可塑性和多样性进化的因素进行前所未有的见解。同时，该项目将培训年轻科学家跨学科免疫学培训，从而有助于形成对免疫反应感兴趣的下一代科学家的形成。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来支持的。