Temperature Scaling of Animal Development

动物发育的温度标度

• 批准号: 2217560
• 负责人: Christopher Hammell
• 金额: $ 100万
• 依托单位: Cold Spring Harbor Laboratory
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2217560&HistoricalAwards=false
• 关键词: Temperature; Scaling; Animal; Development

The development of animals from a single cell to adulthood is a complex operation requiring extreme coordination of billions of molecular events. Remarkably, development of most animal species occurs normally despite radical changes that may occur in the environment that would individually impact these molecular reactions. This property suggests that evolution has selected for and can encode gene regulatory networks that generate similar developmental outcomes despite changing conditions. This proposal aims to understand how animals can maintain the correct timing of gene expression when developing at different temperatures. Specifically, the investigators have developed tools to directly measure how and when animals turn on and off key developmental genes. They will use this system to dissect how changes in global gene expression are maintained across different cells and tissues during development at variable temperatures. This will allow the investigators to determine the unknown architectures of gene expression that are in place to make sure development in varying environments generates similar outcomes. As part of this project they will also provide research experiences for an undergraduate student, and they will perform outreach to minority-serving high schools in New York City.Temperature impacts all biochemical reactions. For multicellular developmental systems, temperature fluctuations pose particular challenges because the orderly morphological progression depends on both spatially and temporally coordinated cellular decisions. It has been shown that overall developmental rates of poikilothermic animals obey Arrhenius scaling, though scaling parameters are genus and even species dependent. Despite the myriad diverse chemical reactions involved, this temperature scaling is uniform, leaving the relative timing of key developmental milestones unchanged. It remains unknown how this is achieved and, more generally, how individual molecular decisions that control developmental processes are buffered against temperature and synchronized within and across tissues to maintain developmental precision. The goal of this project is to uncover the organizational strategy and molecular mechanisms that confer this robustness. The investigators have developed a unique microfluidics methodology that allows high-resolution imaging of gene expression in multiple C. elegans larvae simultaneously throughout post-embryonic development. This technology will enable the investigators to determine how transcriptional patterns of key regulatory molecules are organized at different temperatures and enable them to model how Gene Regulatory Networks (GRNs) that generate these patterns work. The studies put the investigators in a position to now pioneer quantitative in-vivo studies of the temporal patterning GRN.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.

从单个细胞到成年的动物的发展是一个复杂的操作，需要数十亿个分子事件的极端协调。值得注意的是，大多数动物物种的发展通常发生，尽管在环境中可能发生了根本性的变化，从而单独影响这些分子反应。该属性表明，进化已选择并可以编码基因调节网络，尽管条件发生了变化，这些基因调节网络仍会产生相似的发展结果。该建议旨在了解动物在不同温度下发育时如何保持基因表达的正确时机。具体而言，研究人员开发了工具，可以直接测量动物如何和何时打开关键的发育基因。他们将使用该系统来剖析在变化下的发育过程中如何在不同细胞和组织之间保持全球基因表达的变化。这将使研究人员能够确定基因表达的未知架构，以确保在不同环境中开发产生相似的结果。作为该项目的一部分，他们还将为本科生提供研究经验，并将向纽约市少数族裔服务的高中进行宣传。温波会影响所有生化反应。对于多细胞发育系统，温度波动构成了特定的挑战，因为有序的形态进展取决于空间和时间协调的细胞决策。已经表明，尽管缩放参数是属甚至物种依赖的，但poikilothermic Animals的总体发育速率遵守Arrhenius缩放。尽管涉及无数的化学反应，但这种温度缩放是均匀的，使关键发展里程碑的相对时机保持不变。它是如何实现的，更一般而言，如何控制发育过程的单个分子决策如何缓冲温度并在组织内部和整个组织内和跨组织中同步以保持发育精确。该项目的目的是揭示赋予这种鲁棒性的组织策略和分子机制。研究人员开发了一种独特的微流体方法，该方法可以同时在整个胚胎后发育中同时对秀丽隐杆线虫幼虫的基因表达进行高分辨率成像。这项技术将使研究人员能够确定如何在不同温度下组织关键调节分子的转录模式，并使其能够模拟产生这些模式的基因调节网络（GRN）如何工作。这些研究使研究人员现在可以先进对时间模式GRN进行定量的体内研究。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估审查标准，认为值得通过评估值得支持。