Dissecting the Sphingolipid Metabolic and Regulatory Network

鞘脂是植物细胞周围细胞膜中含量最丰富的脂类成分。这种膜将植物细胞与周围环境隔开。鞘脂成分对于植物在不同的生长条件下生存，如干旱和冰冻，以及抵抗病原真菌和细菌的感染的能力是重要的。植物细胞合成的鞘磷脂的量因环境条件的不同而不同。这个项目研究植物如何产生最佳生长所需的神经鞘脂脂。如果鞘脂太少，植物的细胞将无法生长，过量的鞘脂可能会引发细胞死亡。这个项目展示了鞘脂新陈代谢是如何被调节的，并生成了一个计算机模型来预测植物中鞘脂水平的调节。在最适宜的生长条件下和对病原体感染的反应中，研究了鞘磷脂代谢的调节。该项目的结果将使植物育种者和生物技术专家能够预测地改变玉米和大豆等作物中的鞘磷脂新陈代谢。有了这个项目所获得的知识，植物育种者将能够保持植物生产力，以应对干旱、土壤盐分、病原真菌和细菌以及其他环境挑战。该项目让高中生和本科生参与鞘脂研究，以促进STEM教育。研究生学员在计算与实验的融合方面接受了广泛的培训，以解决重要的生物学问题。该项目通过将计算建模与实验方法相结合，解决了植物中鞘磷脂代谢调节及其对生物应激反应的影响方面的基本知识空白。通过对野生型和突变型植物在生物胁迫下的代谢通量分析得出的动力学模型，确定了生物合成和分解代谢反应对鞘磷脂代谢调节的相对贡献。植物突变体和工程酵母菌株的广泛工具箱被用于生化和遗传学研究，旨在了解orosomuclike蛋白发挥中央调节作用的机制。这些调节剂控制因生物压力而产生的神经鞘脂脂的数量和类型。这些研究的发现有助于通过设计-建造-测试-精炼循环来改进迭代动力学模型，以便更定量和更机械地了解植物中鞘磷脂的代谢调节。该项目还通过开发一个包含鞘脂结构多样性、新陈代谢、功能和分析信息的门户网站来推进对植物鞘脂的研究，并传播项目衍生的代谢模型。该奖项反映了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。

Sphingolipids are the most abundant lipid component of the membrane that surrounds plant cells. This membrane separates the plant cell from the surrounding environment. Sphingolipid composition is important for the plant's ability to survive variable growth conditions, such as drought and freezing, and to fight infection from pathogenic fungi and bacteria. Plant cells vary the amount of sphingolipid synthesized depending on environmental conditions. This project examines how plants make the required amount of sphingolipid for optimal growth. If there is too little sphingolipid, the plant's cells will not be able to grow and the presence of excess sphingolipid can trigger cell death. This project shows how sphingolipid metabolism is regulated and generates a computer model to predict the regulation of sphingolipid levels in plants. Regulation of sphingolipid metabolism is investigated under optimal growth conditions and in response to pathogen infection. The results of this project will enable plant breeders and biotechnologists to predictably alter sphingolipid metabolism in crops, such as corn and soybean. With the knowledge derived from this project plant breeders will be able to maintain plant productivity in response to drought, soil salinity, pathogenic fungi and bacteria and other environmental challenges. The project engages high school and undergraduate students in sphingolipid research to advance STEM education. Graduate student participants are trained broadly in the convergence of computation with experimentation to address significant biological questions.The project addresses fundamental gaps in knowledge of sphingolipid metabolic regulation in plants and its impact on biotic stress responses by integrating computational modeling with experimental approaches. Relative contributions of biosynthetic and catabolic reactions for sphingolipid metabolic regulation are determined through a kinetic model derived from metabolic flux analyses of wild-type and mutant plants exposed to biotic stresses. An extensive toolbox of plant mutants and engineered yeast strains are used for biochemical and genetic studies aimed at understanding mechanisms through which orosomucoid-like proteins function as central regulators. These regulators control the amounts and types of sphingolipids produced in response to biological stresses. Findings from these studies contribute to iterative kinetic model improvement through design-build-test-refine cycles for a more quantitative and mechanistic understanding of sphingolipid metabolic regulation in plants. The project also advances the study of plant sphingolipids through development of a web portal that contains information on sphingolipid structural diversity, metabolism, function, and analysis and disseminates project-derived metabolic models.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.