CAREER: Optogel Proteomics: unbiased subcellular proteomics powered by photoreactions in hydrogel

职业：Optogel 蛋白质组学：由水凝胶中的光反应驱动的无偏亚细胞蛋白质组学

• 批准号: 2341058
• 负责人: Xiaoyu Shi
• 金额: $ 67.98万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-07-01 至 2029-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2341058&HistoricalAwards=false
• 关键词: CAREER; Optogel; Proteomics; unbiased; subcellular

Imagine cells as complex cities, where proteins are the citizens, each with specific roles in different districts. For scientists to understand how these cellular cities function, they need to map where each protein citizen lives and works. However, this is quite a challenge because current scientific tools are either not detailed enough or only focus on a few proteins at a time. This NSF CAREER project introduces a new method named Optogel Proteomics, which acts like a high-tech GPS to track proteins with remarkable precision that is smaller than a single cell. By using hydrogels and a powerful microscope, the investigators will isolate and study proteins from exact locations within the cell. The first mission is to explore the nuclear lamina, a meshwork wrapping a cell's nucleus that can change due to cancer or aging, to discover what proteins are present and how they may influence cancer progression and the aging process. This project not only aims to pioneer this new technology but also to share it widely, enhancing research in biology and engineering. Additionally, the project’s leader, a woman scientist, is dedicated to bridging the gender gap in science through special camps and workshops, empowering the next generation of female scientists. This NSF CAREER project seeks to overcome the limitations of subcellular spatial proteomics through the development of Optogel Proteomics. By employing expansion microscopy, photoreactions, and multi-photon microscopy, proteins within precise subcellular locations can be isolated and subsequently analyzed via mass spectrometry (MS). The project's objective is to provide an unbiased, high-resolution proteomic analysis of subcellular structures, with an initial focus on the nuclear lamina, which has been implicated in cancer-related and age-related heterochromatin loss. The novel Optogel Proteomics will be validated against the newly developed super-resolution microscopy method, Label-Retention Expansion Microscopy (LR-ExM). The broader impacts include the dissemination of Optogel Proteomics and LR-ExM, enhancing research capacity in life sciences at minimal costs. The principal investigator will also conduct annual workshops on these spatial analysis technologies and promote gender equity and interdisciplinary science exposure.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.

将细胞想象成复杂的城市，其中蛋白质是公民，每个蛋白质在不同的区域发挥着特定的作用，科学家们需要绘制出每个蛋白质公民生活和工作的位置。目前的科学工具要么不够详细，要么一次只关注几种蛋白质。这个 NSF 职业项目引入了一种名为 Optogel Proteomics 的新方法，它就像高科技 GPS 一样，能够以比地球还小的精度来追踪蛋白质。通过使用水凝胶。借助强大的显微镜，研究人员将从细胞内的确切位置分离和研究蛋白质。第一个任务是探索核层（一种包裹细胞核的网状结构，它会因癌症或衰老而发生变化），以发现存在哪些蛋白质。以及它们如何影响癌症进展和衰老过程。该项目不仅旨在开拓这项新技术，还旨在广泛分享它，加强生物学和工程学的研究。此外，该项目的领导者是一位女科学家，致力于弥合这一问题。通过特别营和该 NSF 职业项目旨在通过开发 Optogel 蛋白质组学来克服亚细胞空间蛋白质组学的局限性。分离并随后通过质谱 (MS) 进行分析 该项目的目标是提供亚细胞结构的公正、高分辨率蛋白质组学分析，并提供初步结果。重点关注核纤层，它与癌症相关和年龄相关的异染色质丢失有关，新型 Optogel 蛋白质组学将针对新开发的超分辨率显微镜方法——标签保留扩展显微镜 (LR-ExM) 进行验证。影响包括 Optogel 蛋白质组学和 LR-ExM 的传播，以最小的成本提高生命科学研究能力。首席研究员还将举办有关这些空间分析的年度研讨会。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。