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Ex vivo single molecule tools to analyze membrane receptor dynamics

用于分析膜受体动力学的离体单分子工具

基本信息

批准号：
10624963
负责人：
Christopher I Richards
金额：
$ 30.32万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-03 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10624963
关键词：
Address Animal Communication Animal Disease Models Animal Model Animals Biological Biological Models Brain Brain region Cardiac Cell Culture Techniques Cells Chemicals Classification Communication Complex Consumption Data Data Analyses Data Set Development Dimerization Disease Encapsulated Environment Exposure to Future Genes Goals Heart High Performance Computing Image In Vitro Knock-in Knock-in Mouse Machine Learning Manuals Measurement Mediating Membrane Membrane Proteins Methodology Methods Monitor Mus Organ Pharmaceutical Preparations Pharmacotherapy Physiological Physiological Processes Play Population Preparation Process Process Measure Property Protein Biosynthesis Protein Dynamics Proteins Regulation Research Research Methodology Research Personnel Role RyR2 Ryanodine Receptor Calcium Release Channel Sampling Signal Transduction System Techniques Technology Testing Therapeutic Time Tissues Training Vesicle animal tissue cell type cluster computing convolutional neural network design imaging capabilities in vivo insight large datasets molecular imaging nanoscale nanovesicle novel open source postsynaptic neurons presynaptic protein purification prototype receptor response sex single molecule stoichiometry technique development therapeutic target tissue preparation tool trafficking

项目摘要

Membrane receptors play a crucial role in many physiological processes throughout the body by mediating communication between cells. Single molecule imaging has been used extensively to study membrane receptor assembly and stoichiometry in vitro using isolated protein and to a lesser extent cell culture. While studies in isolated cellular systems provide insight into many processes, they lack the context of the complex environment present in an animal where communication between cell types residing in tissue is critical for receptor activity. Single- molecule imaging of native proteins synthesized in vivo would provide a direct approach to measure processes, such as receptor dimerization, that regulate physiological activity. However, current methods are not capable of applying single molecule techniques to study the regulation of protein dynamics taking place within the complex environment of an animal. We have made recent advances in the development of ex vivo single molecule techniques to monitor changes in protein assembly that occur within specific organs. The goal of this proposal is to develop and validate ex vivo single molecule tools that provide new capabilities to monitor the properties of oligomeric membrane receptor assembly, resolve cell type and subcellular region specific single membrane receptors, and automate single molecule data analysis using a machine learning platform. This novel ex vivo technology will enable researchers to take a snap shot in time of the membrane receptor dynamics that took place in the mouse and monitor changes in membrane receptor assembly in response to changes in the animal's physiological environment such as disease and exposure to therapeutics.

膜受体在整个身体的许多生理过程中起着至关重要的作用

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gold Ion Beam Milled Gold Zero-Mode Waveguides.

DOI：
10.3390/nano12101755
发表时间：
2022-05-21
期刊：
NANOMATERIALS
影响因子：
5.3
作者：
Messina, Troy C.;Srijanto, Bernadeta R.;Collier, Charles Patrick;Kravchenko, Ivan I.;Richards, Christopher, I
通讯作者：
Richards, Christopher, I

Nicotine induces morphological and functional changes in astrocytes via nicotinic receptor activity.

尼古丁通过烟碱受体活性诱导星形胶质细胞的形态和功能变化。