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设计和验证一个记者鼠标,通过体内成像技术研究TFEB和TFE3活动的动态调节

Electra Brunialti¹, Nicoletta Rizzi², Rita Pinto-Costa³

¹Department of Health Sciences, University of Milan, Milan, Italy.

|March 24, 2024

概括

研究人员开发了CLEARoptimized,这是一种新的生物传感器,用于测量细胞和小鼠中的转录因子EB (TFEB) 和TFE3活性. 该工具有助于开发针对与TFEB/TFE3失调相关的疾病的药物.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
药理学药理学是指药理学的学科.

背景情况:

转录因子TFEB和TFE3调节关键的细胞过程,如自和溶酶体功能.
TFEB/TFE3的失调与各种疾病有关,使它们成为潜在的治疗点.
现有的工具缺乏选择性MiT/TFE调制的特异性和体内能力.

研究的目的:

开发一种基于报告器的创新生物传感器,用于TFEB和TFE3活动的药理分析.
为了能够精确测量TFEB/TFE3介导的转录在活细胞和生物体.
为了促进选择性MiT/TFE调节剂的发现.

主要方法:

对128个TFEB目标基因促进体进行生物信息分析,以确定调控动机.
构建了CLEAR优化的生物传感器,使用了一种新型的促进剂驱动光酶和tdTomato记者.
在细胞培养和记者小鼠中使用生理和药理刺激进行验证.

主要成果:

该CLEAR优化生物传感器准确地实时测量TFEB和TFE3活动.
在细胞和全动物模型 (小鼠) 中证明了实用性.
通过通过各种刺激调节MiT/TFE活动来证实生物传感器有效性.

结论:

CLEARoptimized是一个多功能工具,用于研究自和溶酶体通路.
能够在生物尺度上对TFEB/TFE3活性进行药理分析.
推进针对MiT/TFE相关疾病的治疗策略的开发.

关键词:

自自是一种自的过程.发现药物的发现.光酶是一种光酶.lysosomal 途径的发生对TFEB和TFE3进行非侵入性研究.这是光学成像.

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相关概念视频

Reporter Genes

Reporter Genes

Reporter genes are a type of protein-coding gene that are often tagged to a gene of interest. Once inside a target cell, reporter genes usually produce visually identifiable characteristics like fluorescence and luminescence when expressed along with the gene of interest. Thus, reporter genes “report” the presence or absence of genes of interest in an organism, determine the gene expression pattern, or track the physical location of a DNA segment or protein in the cell.