CAREER: Defining the Role of Lipid Perturbations in Cell Survival

该奖项全部或部分由2021年美国救援计划法案（公法117-2）资助。 脂质是所有脂肪、一些维生素和所有多细胞生物（包括哺乳动物）中不同细胞类型之间的许多信号分子的基本组成部分。 这里的研究将集中在与脑细胞功能和存活相关的脂质上。 通过改变细胞中胆固醇和其他脂质的水平并测量细胞存活率，研究结果将显示这些脂质如何影响正常哺乳动物脑细胞功能。 此外，研究人员将与简亚当斯中学开展合作。 在日常生活中，脂质，特别是胆固醇，通常被认为对人类“有害”。 这项研究说明了胆固醇在细胞功能和功能障碍方面的关键作用。 该项目将开发一种协作教育体验，让中学生了解脂质的生物化学，包括胆固醇，它们与日常生活的关系，并让这些学生了解科学家的一天。 美国救援计划对该项目的资助将在这位研究者职业生涯的关键阶段为她提供支持。脂质稳态和分布的维持对适当的细胞功能和生存至关重要。PI有兴趣了解胆固醇运输，储存和分布对细胞存活的相互作用，特别关注中枢神经系统。 这项工作将调查扰动的胆固醇运输，导致改变脂肪酸和羟基化神经酰胺，从而有助于程序性细胞死亡。 通过PI在生物质谱、生物化学和分子生物学方面的专业知识，结合使用体外和体内研究，将进一步加深我们对细胞维持和存活中这些关键脂质的理解。 除了这个基本的科学目标，该项目将通过与简亚当斯中学合作，为学生制定一个框架，以了解对个人和社会福祉重要的脂质生物化学基本概念，为来自不同背景的学生提供新的经验，该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2)This project seeks to understand how lipid dynamics are crucial for cellular survival. Lipids are essential components of all fats, some vitamins, and many signaling molecules between different cell types in all multicellular creatures, including mammals. The studies here will focus on lipids related to brain-cell function and survival. By changing the levels of cholesterol and other lipids in cells and measuring cell survival, the findings will show how these lipids affect normal mammalian brain-cell function. In addition, the researchers will carry out a partnership with Jane Addams Middle School. In everyday life, lipids, and specifically cholesterol, are often perceived as “bad” for humans. The research illustrates the critical role of cholesterol both in terms of cellular function and dysfunction. The project will develop a collaborative educational experience to expose middle school students to the biochemistry of lipids including cholesterol, how they are related to everyday life, as well as to provide these students a glimpse of a day in the life of a scientist. American Rescue Plan funding of this project will provide support for this investigator at a critical stage in her career.Maintenance of lipid homeostasis and distribution is crucial for proper cellular function and survival. The PI is interested in understanding the interplay of cholesterol trafficking, storage, and distribution on cellular survival, with a specific focus on the central nervous system. This work will investigate perturbations of cholesterol trafficking which results in alterations of fatty acids and hydroxylated ceramides and thereby contributing to programmed cell death. Use of a combination of in vitro and in vivo studies by means of the PI’s expertise in biological mass spectrometry, biochemistry, and molecular biology will further our understanding of these critical lipids in cell maintenance and survival. In addition to this basic science goal, the project will benefit society through a collaborative effort with Jane Addams Middle School to develop a framework for students to understand basic concepts in lipid biochemistry important for individual and societal well-being, to provide a new experience for students from differing backgrounds, and to engage these students with futures in scientific careers.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.