Transcriptional Signatures of 3D Liver Mimetic Architectures

3D 肝脏模拟架构的转录特征

• 批准号: 0933225
• 负责人: Padmavathy Rajagopalan
• 金额: $ 30.29万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0933225&HistoricalAwards=false
• 关键词: Transcriptional; Signatures; 3D; Liver; Mimetic

0933225RajagopalanCommunication between different cell types is essential for the proper function of many human organs. What signals different cell types transfer between each other and how they respond to these signals is far from completely understood. This project studies the liver, which is one of the most important organs in the human body. Using a discovery-driven and inter-disciplinary approach, the goal of this project is to understand communications between the two main cell types in the liver, namely, hepatocytes and liver sinusoidal endothelial cells. The scientific objectives of the project are the following:Objective I: Assemble three-dimensional liver mimics composed of hepatocytes and endothelial cells and collect temporal gene expression data using DNA microarrays.Objective II: Compute molecular interaction networks that capture the response of hepatocytes and endothelial cells in liver mimics.Intellectual Merit. The transformative nature of this project stems from the use of three-dimensional liver mimics to systematically probe and untangle the complex phenomena underlying cellular interactions in the liver. The integration of genome-wide transcriptional measurements in such liver mimics with molecular interaction networks will reveal the signals that mediate communications between hepatocytes and liver sinusoidal endothelial cells. Together, these studies will lead to deeper insights into the modes of interactions between cells types in the liver and their role in the maintenance of adult liver function.Broader Impacts. A comprehensive understanding of biomimetic spatial organization and choreographed communication between different cell types has profound implications for tissue engineering. Information gleaned from this project will provide a sound theoretical basis for the design of the next generation of tissue-engineered livers. Outreach to middle school students and to ethnically diverse female high school students through summer camps sponsored by Virginia Tech's Center for Enhancement in Engineering Diversity will introduce students to the notion of interdisciplinary research and demonstrate how collaborative advances in engineering and computer science can have a direct impact on human health.

不同细胞类型之间的交流对于许多人体器官的正常功能至关重要。不同类型的细胞之间传递什么信号以及它们如何对这些信号作出反应还远未完全了解。这个项目研究的是肝脏，它是人体最重要的器官之一。采用发现驱动和跨学科的方法，该项目的目标是了解肝脏中两种主要细胞类型，即肝细胞和肝窦内皮细胞之间的通信。该项目的科学目标如下：目标一：组装由肝细胞和内皮细胞组成的三维肝脏模拟物，并使用DNA微阵列收集时间基因表达数据。目的二：计算分子相互作用网络，捕捉肝细胞和内皮细胞在肝模拟物中的反应。知识价值。该项目的变革性质源于使用三维肝脏模拟系统地探测和解开肝脏中细胞相互作用的复杂现象。这种肝脏模拟物的全基因组转录测量与分子相互作用网络的整合将揭示介导肝细胞和肝窦内皮细胞之间通信的信号。总之，这些研究将导致更深入地了解肝脏细胞类型之间的相互作用模式及其在维持成人肝功能中的作用。更广泛的影响。全面了解仿生空间组织和不同细胞类型之间的编排通信对组织工程具有深远的意义。从该项目中收集的信息将为下一代组织工程肝脏的设计提供良好的理论基础。通过弗吉尼亚理工大学工程多样性增强中心赞助的夏令营，向中学生和种族多样化的女高中生进行推广，将向学生介绍跨学科研究的概念，并展示工程和计算机科学的合作进步如何对人类健康产生直接影响。