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.

有了这个奖项，化学部的生命过程化学项目资助了来自利哈伊大学的Kerney Jebrell格洛弗、Nathan Wittenberg和Wonnberg Im博士研究脂滴和与脂滴相关的蛋白质油质蛋白。脂滴是在细胞内发现的球状实体，储存能量以供将来使用。油质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。这项研究的目标是使用生物化学，生物物理学和计算方法更好地研究油质蛋白的结构以及它如何保持脂滴的完整性。这项研究的结果将被应用于探索脂滴的潜在用途，以消除药物和个人护理产品的污染物从水道。本研究计划将为本科生提供研究机会，并在课程的最后阶段为学生设计一套实验室实验，以探索脂滴吸收环境毒素的作用。本研究计划的目的是了解油质蛋白在脂滴体内平衡中的作用。脂滴是准球形细胞实体，其充当高能代谢物的储存器，并且由被磷脂单层包裹的三酰甘油核心组成，所述磷脂单层被蛋白质油质蛋白广泛地打断。油质蛋白的三维结构将使用NMR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的组合来建模。此外，将通过突变研究来研究油质蛋白防止脂滴聚结的机制。最后，合成脂滴作为污染螯合剂的能力，用于从水道中去除药物和个人护理产品，将通过改变液滴的核心极性进行系统研究和优化。拟议的工作的一个重要成果将是开发一个'Membrane Builder'扩展到CHARMM分子模拟程序的图形界面。CHARMM-GUI将免费提供给希望在脂滴上运行分子动力学模拟的研究人员。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。