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

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化生活的机制。深海的体积远远大于地球上所有其他栖息地的总和，但只有高度专门化的生物才能在极端条件下生存下来。深海动物是如何在冰冻的温度和挤压压力下保持它们的细胞功能的--在表面上是这样的几百倍？令人惊讶的是，一旦动物适应了深海，表面条件往往对它们来说变得极端，除了深海，它们无法在任何地方生存。研究人员将重点研究深海动物的细胞膜--对压力和温度非常敏感的分子结构。该团队将在深海勘探、基因组学、脂质组学、生物物理学、合成生物学和计算机建模方面应用最新方法，以揭示允许在不同海洋环境中生存的分子和细胞特征。成功将带来有关生命生化极限的新知识，并使人们深入了解环境变化可能如何影响海洋动物的多样性和丰富性。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不同领域的信息时，就会取得突破。因此，该项目将为博士生提供跨学科的培训，以培养出接受过综合生物学研究方法培训的新一代不同的科学家。该团队的发现还将与全国各地的教育工作者合作，纳入针对K-12学生的综合教育课程。该项目使用鞭毛虫--通常被称为梳状水母--作为一个模型系统，以发现生物体耐受深海极端条件的能力所依据的规则。许多科学家从未见过活的鞭毛虫，但这个门代表了研究适应极端环境条件的一个极好的模式系统。鞭毛虫生活在温度(-2摄氏度至30摄氏度)和压力(1至700巴)的广泛范围内，它们一致地适应了这些条件，在非常深和很浅的生境中也发现了密切相关的物种。最近，在实验室培养几代人中保持它们已经成为可能，并且有高质量的转录本和染色体规模的基因组可用。薄层组织基本上是鞭毛虫与周围水的区别所在，因此适应必须集中在细胞水平上。推动这个项目的总体假设是，脂代谢的适应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、全动物实验、加压生化表征、高压小角X射线散射、分子动力学模拟和合成生物学，以揭示Ctenopore膜适应深海的遗传和物理化学机制。从综合观察中得出的预测将通过在微生物中进行脂肪代谢工程来检验。出现的“规则”将与海洋生物学、生物技术、食品科学和极端条件下动物的生理学相关。这一奖项反映了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。

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.