Molecular signaling in mechanobiology regulation by single-cell analyses using bioinformatics approach

使用生物信息学方法通过单细胞分析进行机械生物学调节中的分子信号传导

• 批准号: 2327144
• 负责人: Yi-Xian Qin
• 金额: $ 89.82万
• 依托单位: SUNY at Stony Brook
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-10-01 至 2026-09-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2327144&HistoricalAwards=false
• 关键词: Molecular; signaling; mechanobiology; regulation; single

Homeostasis in living animals and in plants is a self-regulating process by which an organism can maintain internal stability while adjusting to changing external conditions. Numerous molecular mechanisms are involved in these regulatory processes, including cell sensing and communication, intracellular and membrane excitation, and extracellular connections. Mechanobiology enhances cellular sensing genes and channels controlling cell-cell communication, intracellular and membrane excitation, and extracellular connections. The project will develop a single-cell multiplex in situ tagging (scMIST) system combined with advanced machine leaning algorithms through successive rounds of labeling and imaging to effectively achieve a multiplexity of thousands of data points using a common fluorescence microscope and a simple procedure in a typical biological laboratory setting, which has the potential to revolutionize the field of mechanical biology. The project will be committed to outreach and recruitment efforts targeting minority students and those interested in STEM fields.Enhancing cellular viability and motility induced by dynamic physical stimulation is one of the vital components and factors in the biological system’s response to mechano-transduction and regeneration. The project will focus on 1) generating an integrated database of cellular differentiation and adaptation through Ca^(2+) release, Wnt/beta-Catenin signaling, and T-cell immuno-pathway with and without Piezo1 mitigation, and inter- and intra-cellular communication, and cell differentiation; 2) evaluating dynamic loading on single-cell DNA-encoded sequencing by quantifying signaling proteins and surface markers from various cell and proteins; 3) developing machine learning and deep learning algorithms, using R-Studio and bioinformatics platforms; and 4) developing an AI-based framework for bioinformatics analysis to visualize high-dimensional data, classify cell subtypes by both functions and phenotypes, and determine the signaling networks of each subtypes. This study will further enhance our understanding of the impact of the external environment on the living system and its adaptation at the cellular, molecular, and protein levels. The results of the project will be made to public through the lab website, https://you.stonybrook.edu/qinlab/home/.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.

在活的动物和植物中，稳态是一种自我调节的过程，通过这种过程，生物体可以保持内部稳定，同时适应不断变化的外部条件。许多分子机制参与这些调节过程，包括细胞传感和通信，细胞内和膜兴奋，和细胞外连接。机械生物学增强细胞传感基因和控制细胞间通讯、细胞内和膜兴奋以及细胞外连接的通道。该项目将开发一种单细胞多重原位标记（scMIST）系统，结合先进的机器学习算法，通过连续几轮的标记和成像，使用普通荧光显微镜和一个简单的程序在典型的生物实验室环境中有效地实现数千个数据点的多重性，这有可能彻底改变机械生物学领域。 该项目将致力于针对少数民族学生和对STEM领域感兴趣的学生开展外联和招聘工作。增强动态物理刺激诱导的细胞活力和运动性是生物系统对机械转导和再生反应的重要组成部分和因素之一。该项目将集中于1）通过Ca^（2+）释放、Wnt/β-连环蛋白信号传导、T细胞免疫通路（有或没有Piezo 1抑制）、细胞间和细胞内通讯以及细胞分化，生成细胞分化和适应的综合数据库; 2）通过定量来自各种细胞和蛋白质的信号蛋白和表面标志物来评估单细胞DNA编码测序的动态加载; 3）使用R-Studio和生物信息学平台开发机器学习和深度学习算法; 4）开发基于AI的生物信息学分析框架，可视化高维数据，通过功能和表型对细胞亚型进行分类，并确定每个亚型的信号网络。这项研究将进一步提高我们对外界环境对生命系统的影响及其在细胞、分子和蛋白质水平上的适应性的认识。该项目的结果将通过实验室网站向公众公布，https://you.stonybrook.edu/qinlab/home/.This奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。