Transcriptional Signatures of 3D Liver Mimetic Architectures

不同细胞类型之间的交流对于人体许多器官的正常功能是必不可少的。不同类型的细胞之间相互传递什么信号，以及它们如何对这些信号做出反应，目前还远未完全了解。这个项目研究肝脏，这是人体最重要的器官之一。利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之间的联系，即肝细胞和肝窦内皮细胞。该项目的科学目标如下：目的一：组装由肝细胞和内皮细胞组成的三维肝脏模型，并利用DNA微阵列收集时间基因表达数据。目标二：计算捕捉肝细胞和内皮细胞在肝脏模拟中的反应的分子相互作用网络。这个项目的变革性源于使用三维肝脏模拟来系统地探索和解开肝脏中细胞相互作用的复杂现象。将全基因组转录测量与分子相互作用网络相结合，将揭示肝细胞和肝窦内皮细胞之间的信号传递。总而言之，这些研究将导致对肝脏细胞类型之间相互作用的模式以及它们在维持成人肝功能中的作用的更深入的洞察。全面了解不同细胞类型之间的仿生空间组织和精心设计的交流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，面向中学生和不同种族的女高中生，将向学生介绍跨学科研究的概念，并展示工程学和计算机科学的合作进步如何对人类健康产生直接影响。

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.