Physical regulation of cellular respiration by membrane lipid composition

膜脂成分对细胞呼吸的物理调节

• 批准号: 1715681
• 负责人: Jay Keasling
• 金额: $ 62.53万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1715681&HistoricalAwards=false
• 关键词: Physical; regulation; cellular; respiration; membrane

The chemical energy that cells use for growth is generated using respiration, a universal set of reactions that occur partly within lipid membranes. Lipid composition is used by cells to modulate the properties of their membranes, which could act as important physical structures for reactions that occur during respiration. In this project, novel synthetic biology approaches will be used to investigate biophysical roles for lipid chemistry and membrane structure in respiratory activity. This research will provide mechanistic insight into respiratory function and cell physiology that is applicable to a wide variety of organisms and is relevant to understanding the interplay of diet and disease in human health. In addition to the research activities, this grant will support education and outreach efforts that focus on scientific training for underprivileged high school and undergraduate students. These efforts will teach students fundamental concepts in metabolism and provide hands-on experience with emerging biotechnology research projects in order to support their future careers in science and technology.Efforts to engineer fatty acid composition in bacteria have led to the observation that fluidizing lipid components, such as unsaturated lipids, act as a general regulator of respiratory metabolism. The project will test the hypothesis that respiratory flux by is controlled by the lipid-mediated diffusion rates of electron transport chain components. This will be done with a combination of biophysical measurements, physiological experiments, and physical modeling of bacterial respiratory chains. Lipid composition varies tremendously among prokaryotes and this could partly be understood through differences in their metabolic requirements. The project will therefore use synthetic biology approaches to assess the metabolic effects of isoprenoid-based membrane components that modulate membrane structure in a heterologous bacterial host. Lipid composition is also tightly regulated in mitochondrial membranes, which carry out respiration in all eukaryotic cells. The project will use engineered yeast strains to systematically investigate the role of fatty acid composition in mitochondrial structure and respiratory activity. These systems will serve as models for understanding how lipid composition can affect metabolic functions and may be broadly applicable to many important processes.

细胞用于生长的化学能是通过呼吸作用产生的，呼吸作用是一种部分发生在脂质膜内的普遍反应。脂质成分被细胞用来调节它们的膜的性质，膜可以作为呼吸过程中发生的反应的重要物理结构。在这个项目中，新的合成生物学方法将被用来研究生物物理作用的脂质化学和膜结构的呼吸活动。这项研究将提供对呼吸功能和细胞生理学的机械见解，适用于各种生物体，并与理解人类健康中饮食和疾病的相互作用有关。除了研究活动，这笔赠款将支持教育和推广工作，重点是对贫困高中和本科生的科学培训。这些努力将教会学生新陈代谢的基本概念，并提供新兴生物技术研究项目的实践经验，以支持他们未来的科学和技术事业。对细菌中脂肪酸组成的工程设计的努力已经导致观察到流化脂质成分，如不饱和脂质，作为呼吸代谢的一般调节剂。该项目将测试的假设，即呼吸通量由脂质介导的电子传递链组件的扩散速率控制。这将通过生物物理测量，生理实验和细菌呼吸链的物理建模相结合来完成。原核生物之间的脂质组成变化很大，这可以部分地通过它们的代谢需求的差异来理解。因此，该项目将使用合成生物学方法来评估基于类异戊二烯的膜组分的代谢效应，这些膜组分调节异源细菌宿主中的膜结构。脂质组成也在线粒体膜中受到严格调节，线粒体膜在所有真核细胞中进行呼吸。该项目将使用工程酵母菌株系统地研究脂肪酸组成在线粒体结构和呼吸活性中的作用。这些系统将作为模型，了解脂质成分如何影响代谢功能，并可能广泛适用于许多重要的过程。

项目成果

Synthetic Biology for Fundamental Biochemical Discovery

• DOI: 10.1021/acs.biochem.8b00915
• 发表时间: 2019-03-19
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Budin, Itay;Keasling, Jay D.
• 通讯作者: Keasling, Jay D.

Viscous control of cellular respiration by membrane lipid composition

• DOI: 10.1126/science.aat7925
• 发表时间: 2018-12-07
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Budin, Itay;de Rond, Tristan;Keasling, Jay D.
• 通讯作者: Keasling, Jay D.