CAS-Biophysical Studies of Lipid Droplets and their Associate Proteins

CAS-脂滴及其相关蛋白的生物物理研究

• 批准号: 2203362
• 负责人: Kerney Glover
• 金额: $ 50.66万
• 依托单位: Lehigh University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2203362&HistoricalAwards=false
• 关键词: CAS; Biophysical; Studies; Lipid; Droplets

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Drs. Kerney Jebrell Glover, Nathan Wittenberg, and Wonpil Im from Lehigh University to investigate lipid droplets and the protein oleosin that is associated with lipid droplets. Lipid droplets are sphere-like entities found within cells that store energy for future use. Oleosin is a protein that is important to help stabilize these droplets in plant cells. The goals of this research are to use biochemical, biophysical, and computational methods better to study the structure of the oleosin protein and how it maintains the integrity of lipid droplets. Results from this study will be applied to explore the potential use of lipid droplets to remove pharmaceutical and personal care product pollutants from waterways. The project will provide research opportunities to undergraduate students and will develop a set of laboratory experiments in a capstone course for students to explore the use of lipid droplets to absorb environmental toxins.The objective of this research project is to understand the role that oleosin plays in lipid droplet homeostasis. Lipid droplets are quasi-spherical cellular entities that function as reservoirs of high-energy metabolites and consist of a triacylglycerol core encapsulated by a phospholipid monolayer that is punctuated extensively with the protein oleosin. The three-dimensional structure of oleosin will be modeled using a combination of NMR spectroscopy, Förster resonance energy transfer (FRET)-based fluorescent spectroscopy, and all-atom molecular dynamics simulations. Additionally, the mechanism by which oleosin prevents the coalescence of lipid droplets will be investigated through mutational studies. Finally, the ability of synthetic lipid droplets to act as pollution sequestration agents for the removal of pharmaceuticals and personal care products from waterways will be systematically investigated and optimized by varying the core polarity of the droplet. An important result of the proposed work will be the development of a ‘Membrane Builder’ extension to the graphical interface for the CHARMM molecular simulation program. This CHARMM-GUI will be made freely accessible to researchers who desire to run molecular dynamics simulations on lipid droplets.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.

该奖项由化学系生命过程化学项目资助利哈伊大学的Kerney Jebrell Gever、Nathan Wittenberg和Wonpil Im博士研究脂滴和与脂滴相关的蛋白质油球。脂滴是细胞内发现的球状实体，可以储存能量供未来使用。油球蛋白是一种重要的蛋白质，有助于稳定植物细胞中的这些液滴。这项研究的目标是更好地使用生化、生物物理和计算方法来研究油球蛋白的结构以及它如何维持脂滴的完整性。这项研究的结果将被应用于探索使用脂滴去除水道中的药物和个人护理产品污染物的可能性。该项目将为本科生提供研究机会，并将在顶峰课程中为学生开发一套实验室实验，以探索使用脂滴吸收环境毒素。本研究项目的目的是了解油球蛋白在脂滴动态平衡中所起的作用。脂滴是一种准球形的细胞实体，其功能是储存高能代谢物，并由被磷脂单分子层包裹的三酰甘油核心组成，磷脂单分子层广泛地点缀着蛋白质油球蛋白。将结合核磁共振光谱、基于Förster共振能量转移(FRET)的荧光光谱和全原子分子动力学模拟来模拟油球蛋白的三维结构。此外，油球蛋白阻止脂滴结合的机制将通过突变研究进行研究。最后，将通过改变合成脂滴的核心极性，系统地研究和优化合成脂滴作为污染物隔离剂从水道中清除药品和个人护理产品的能力。这项拟议工作的一个重要成果将是为CHARMM分子模拟程序开发图形界面的‘膜生成器’扩展。希望对脂滴进行分子动力学模拟的研究人员可以免费访问CHARMM-图形用户界面。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。