CAREER: Defining the Role of Lipid Perturbations in Cell Survival

该奖项的全部或部分资金是根据2021年美国救援计划法案(公法117-2)提供的。该项目旨在了解脂质动力学如何对细胞生存至关重要。在包括哺乳动物在内的所有多细胞生物中，脂类是所有脂肪、一些维生素和不同细胞类型之间的许多信号分子的基本成分。这里的研究将集中在与脑细胞功能和生存相关的脂类上。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，这些发现将显示这些脂类如何影响哺乳动物的正常脑细胞功能。此外，研究人员还将与简·亚当斯中学开展合作。在日常生活中，脂质，特别是胆固醇，经常被认为对人类“有害”。这项研究阐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，让中学生接触包括胆固醇在内的血脂的生物化学，它们与日常生活的关系，以及让这些学生一瞥科学家的一天。美国救援计划资助这一项目将在她职业生涯的关键阶段为这位研究员提供支持。维持脂质稳态和分布对正常的细胞功能和生存至关重要。PI感兴趣的是了解胆固醇运输、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。这项工作将调查胆固醇转运的扰动，这会导致脂肪酸和羟化神经酰胺的变化，从而导致细胞程序性死亡。利用PI在生物质谱学、生物化学和分子生物学方面的专业知识，结合体外和体内研究，将进一步加深我们对这些关键脂质在细胞维持和生存中的理解。除了这个基础科学目标，该项目还将通过与简·亚当斯中学的合作来造福社会，为学生建立一个框架，让他们了解对个人和社会福祉至关重要的脂质生物化学的基本概念，为来自不同背景的学生提供新的体验，并让这些学生参与到科学职业生涯中来。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。

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.