Collaborative Research: IntBIO: Rules for cell membranes in the extremes of the deep sea

合作研究：IntBIO：深海极端条件下细胞膜的规则

• 批准号: 2316458
• 负责人: Itay Budin
• 金额: $ 76.83万
• 依托单位: University of California-San Diego
• 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: 2023-07-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2316458&HistoricalAwards=false
• 关键词: Collaborative; Research; IntBIO; Rules; cell

In this project, a cross-disciplinary team of scientists will uncover the mechanisms underlying how animals specialize for life in the deep ocean. The volume of the deep sea is vastly larger than all other habitats on earth combined, but only highly specialized organisms can survive its extreme conditions. How do deep-sea animals keep their cells functioning under freezing temperatures and crushing pressures — hundreds of times that at the surface? In a surprising twist, once animals have adapted to the deep sea, surface conditions often turn extreme to them, and they fail to survive anywhere except in the deep sea. The researchers will focus on the cell membranes of deep-sea animals — molecular structures that are very sensitive to pressure and temperature. The team will apply the latest methods in deep-ocean exploration, genomics, lipidomics, biophysics, synthetic biology, and computer modeling to uncover the molecular and cellular features that allow for survival in different marine environments. Success will lead to new knowledge about the biochemical limits of life and give insight into how environmental changes might affect diversity and abundance of marine animals. Broad preparation is an essential aspect of transformative research, because breakthroughs come when scientists integrate information from a variety of domains. Thus, this project will provide cross-disciplinary training for Ph.D. students to produce a new generation of diverse scientists who are trained in integrative approaches to biological research. The team’s findings will also be incorporated into an integrative education curriculum for K-12 students in partnership with educators across the country.The project uses ctenophores — commonly called comb jellies — as a model system to discover rules that underlie an organism’s ability to tolerate the extreme conditions found in the deep sea. Many scientists have never seen a live ctenophore, yet this phylum represents an excellent model system for the study of adaptation to extreme environmental conditions. Ctenophores inhabit a wide range of temperatures (-2°C to 30°C) and pressures (1 to 700 bar), and they have convergently adapted to these conditions, with closely related species also being found in very deep and very shallow habitats. Recently it has become possible to maintain them in lab culture for several generations, and there are high-quality transcriptomes and chromosome-scale genomes available. Thin layers of tissue are essentially all that distinguishes a ctenophore from the surrounding water, so adaptation must be focused at the cellular level. The overall hypothesis driving this project is that adaptations in lipid metabolism can be used to overcome the inhibition of cell-membrane dynamics by pressure. The project combines bioinformatics, whole-animal experiments, pressurized biochemical characterization, high-pressure small-angle x-ray scattering, molecular dynamics simulations, and synthetic biology to uncover the genetic and physicochemical mechanisms by which ctenophore membranes adapt to the deep ocean. Predictions that emerge from integrated observations will be tested by engineering lipid metabolism in microorganisms. The “rules” that emerge will be relevant to marine biology, biotechnology, food science, and the physiology of animals subjected to extreme conditions.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.

在这个项目中，一个跨学科的科学家团队将揭示动物如何在深海中专门生活的机制。深海的体积远远大于地球上所有其他栖息地的总和，但只有高度专业化的生物才能在极端条件下生存。深海动物是如何在冰冻温度和破碎压力下保持细胞功能的--这些压力是表面的数百倍？令人惊讶的是，一旦动物适应了深海，表面条件往往会变得极端，除了在深海，它们无法在任何地方生存。研究人员将专注于深海动物的细胞膜-对压力和温度非常敏感的分子结构。该团队将应用深海勘探，基因组学，脂质组学，生物物理学，合成生物学和计算机建模的最新方法，以揭示允许在不同海洋环境中生存的分子和细胞特征。成功将带来关于生命的生化极限的新知识，并深入了解环境变化如何影响海洋动物的多样性和丰度。广泛的准备是变革性研究的一个重要方面，因为当科学家整合来自各个领域的信息时，突破就会出现。因此，本项目将为博士生提供跨学科的培训。学生培养新一代多样化的科学家，他们接受生物研究综合方法的培训。该团队的研究结果还将与全国各地的教育工作者合作，纳入K-12学生的综合教育课程。该项目使用栉水母-通常称为梳状水母-作为模型系统，以发现生物体耐受深海极端条件能力的规则。许多科学家从未见过活的栉水母，但这个门是研究适应极端环境条件的一个很好的模型系统。栉水母的栖息地温度（-2 ° C至30°C）和压力（1至700巴）范围很广，它们已经逐渐适应了这些条件，在非常深和非常浅的栖息地也发现了密切相关的物种。最近，在实验室培养中将它们保持几代已经成为可能，并且有高质量的转录组和染色体规模的基因组可用。薄的组织层基本上是区分栉水母和周围水的唯一标志，所以适应必须集中在细胞水平上。推动这一项目的总体假设是，脂质代谢的适应性可以用来克服压力对细胞膜动力学的抑制。该项目结合了生物信息学，整体动物实验，加压生化表征，高压小角度x射线散射，分子动力学模拟和合成生物学，以揭示栉水母膜适应深海的遗传和物理化学机制。从综合观察中出现的预测将通过微生物中的脂质代谢工程进行测试。该奖项反映了NSF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。