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Red and Far-Red Fluorescent Biosensors for Compartmentalized Redox Signaling

用于分隔氧化还原信号传导的红色和远红荧光生物传感器

基本信息

批准号：
9975915
负责人：
Huiwang Ai
金额：
$ 37.84万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-05 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975915
关键词：
Aging Animal Model Basic Science Biology Biosensor Cancer Etiology Cell Compartmentation Cell Nucleus Cell model Cells Chemicals Color Coupled Coupling Cytosol Detection Development Disease Doxorubicin Drug Screening Endoplasmic Reticulum Engineering Epidermal Growth Factor FDA approved Fluorescence Glutathione Goals Human Hydrogen Peroxide Image Imaging Device Individual Inflammatory Intervention Laboratories Lead Libraries Light Measurement Measures Methods Mitochondria Molecular Monitor Nitrogen Nuclear Oncology Organism Oxidation-Reduction Oxidative Stress Oxygen Penetration Pharmaceutical Preparations Phosphotransferases Photons Physiological Process Protein Disulfide Isomerase Proteins Regulation Reporting Research Sensory Signal Transduction Stimulus Sulfhydryl Compounds Sulfur TXN gene Technology Tissues Toxicology Work absorption animal imaging base biomaterial compatibility chemotherapy multiplexed imaging mutant novel novel therapeutics oxidation public health relevance ratiometric red fluorescent protein response sensor spatiotemporal subcellular targeting technology research and development tool toxicant translational study whole animal imaging

项目摘要

ABSTRACT Redox biology has been increasingly recognized as one of the key themes in cell signaling. A major obstacle in this field is the lack of capabilities to monitor and measure clearly defined redox processes in live cells (including subcellular domains in live cells), tissues, or organisms. The goal of this 4-year project, submitted in response to PAR-17-045 “Focused Technology Research and Development”, is to expand the fluorescent protein toolbox for red and far-red fluorescent biosensors that can be used to image compartmentalized, thiol-based redox signaling in live cells and organisms. In this project, we aim to advance the fluorescent biosensor technology in the following aspects : (1) we will expand fluorescent-protein-based biosensors for additional redox parameters, including the redox of thioredoxin and protein disulfide isomerase (PDI) in various cell compartments, such as the nucleus, cytosol, mitochondria, and endoplasmic reticulum (ER); (2) we will expand the colors of fluorescent-protein-based redox biosensors to red and far-red; (3) we will validate these new biosensors and demonstrate the use of fluorescent-protein-based biosensors in compatible colors for multicompartment/multiplex imaging. Because UV or blue light, which can induce intracellular oxidation, is not needed to excite red and far- red fluorescent biosensors, our work will increase the biocompatibility of fluorescent-protein-based redox biosensors. Furthermore, red and far-red biosensors will assist in whole-animal imaging, since compared to green ones, they reduce tissue absorption and scattering. This project will lead to important imaging tools that may accelerate the understanding of redox regulation and signaling. As with the transformative impact of fluorescent-protein-based kinase sensors, we expect that these redox biosensors will enable and transform a large array of basic and translational studies.

摘要