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

University Of California-Irvine, Irvine CA

Investigators

Abstract

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.