Dissecting the Sphingolipid Metabolic and Regulatory Network

剖析鞘脂代谢和调节网络

基本信息

批准号：
1818297
负责人：
Edgar Cahoon
金额：
$ 75万
依托单位：
University of Nebraska-Lincoln
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1818297&HistoricalAwards=false
关键词：
Dissecting Sphingolipid Metabolic Regulatory Network

项目摘要

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.

鞘脂是围绕植物细胞的膜中最丰富的脂质成分。该膜将植物细胞与周围环境区分开。鞘脂组成对于植物能够在干旱和冷冻等可变生长条件下生存以及与致病真菌和细菌感染的感染很重要。根据环境条件，植物细胞改变合成的鞘脂量。该项目研究了植物如何使所需量的鞘脂以达到最佳生长。如果鞘脂太少，植物的细胞将无法生长，并且过量的鞘脂的存在会触发细胞死亡。该项目显示了如何调节鞘脂代谢并生成计算机模型以预测植物中鞘脂水平的调节。在最佳生长条件下研究并响应病原体感染，研究了鞘脂代谢的调节。该项目的结果将使植物育种者和生物技术学家能够可预测地改变玉米和大豆等农作物中的鞘脂代谢。借助该项目的知识，植物育种者将能够响应干旱，土壤盐度，致病真菌和细菌以及其他环境挑战，以维持植物的生产力。该项目吸引了高中和本科生进行鞘脂研究，以提高STEM教育。研究生参与者经过广泛的培训，即通过实验来解决计算的融合，以解决重大的生物学问题。该项目解决了植物中鞘脂代谢调节的知识的基本差距及其对生物压力反应的影响，通过将计算模型与实验方法相结合。生物合成和分解代谢反应对鞘脂代谢调节的相对贡献是通过源自暴露于生物胁迫的野生型和突变植物的代谢通量分析的动力学模型来确定的。广泛的植物突变体和工程酵母菌菌株的工具箱用于生化和遗传研究，旨在理解类细胞类细胞样蛋白作为中心调节剂的机制。这些调节器控制着响应生物胁迫而产生的鞘脂的量和类型。这些研究的发现有助于通过设计建造测试循环循环改进迭代动力学模型，从而对植物中鞘脂代谢的调节有了更定量和机械的理解。该项目还通过开发网络门户的开发来推进植物鞘脂的研究，该网站包含有关鞘脂的结构多样性，代谢，功能和分析的信息，并传播了项目衍生的新陈代谢模型。该奖项反映了NSF的法规任务，并认为通过基金会的知识优点和广泛的critia criter scritia criter scritia criter scritia criter criter criter criter criter critia criter critia critia criter critia critia critia critia criter critia criter critia criter critia又值得通过评估。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Structural insights into the regulation of human serine palmitoyltransferase complexes

人丝氨酸棕榈酰转移酶复合物调节的结构见解

DOI：
10.1096/fasebj.2021.35.s1.04920
发表时间：
2021
期刊：
The FASEB Journal
影响因子：
0
作者：
Lee, Chia‐Hsueh;Wang, Yingdi;Niu, Yiming;Zhang, Zhe;Gable, Kenneth;Gupta, Sita;Somashekarappa, Niranjanakumari;Han, Gongshe;Zhao, Hongtu;Myasnikov, Alexander
通讯作者：
Myasnikov, Alexander

The ORMs interact with transmembrane domain 1 of Lcb1 and regulate serine palmitoyltransferase oligomerization, activity and localization