Collaborative Research: RECODE: Directed Differentiation of Human Liver Organoids via Computational Analysis and Engineering of Gene Regulatory Networks

合作研究：RECODE：通过基因调控网络的计算分析和工程定向分化人类肝脏类器官

• 批准号: 2134998
• 负责人: Ziv Bar-Joseph
• 金额: $ 43.51万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2134998&HistoricalAwards=false
• 关键词: Collaborative; Research; RECODE; Directed; Differentiation

Organoids are group of cells produced from stem cells that mimic closely structure and functions of human organs. Organoids can be used for modeling the development of human diseases and for testing newly produced medicines. However, there is a need for generation of human organoids with better function and less variability. This project aims to use genetic based analysis and engineering to control stem cell differentiation towards human liver cells and improve the final manufacturing outcome of liver organoids. As part of the activities in this project, graduate and undergraduate students will be trained and short educational video clips will be made for online education and public engagement.This RECODE project will address biotechnology challenges of in vitro liver organoid engineering such as maturity, vascular formation, and reproducibility. To this end, synthetic biology, stem cell engineering, and systems biology will be integrated to develop a platform for autonomous differentiation of human induced pluripotent stem cells to liver organoids. Studies will be performed in two independent objectives to: 1) develop synthetic gene circuits for multistep differentiation in liver organoids and 2) identify lineage plasticity regulators during differentiation to control final cell fates in engineered organoids. The understanding gained through this work will address knowledge gaps applicable to cellular differentiation, human liver maturation, and vascular formation. This project will also provide support for the development of a strong STEM workforce through novel online education and public outreach activities surrounding stem cell engineering.This RECODE award is co-funded by the Systems and Synthetic Biology Cluster in the Division of Molecular and Cellular Biosciences and the Engineering Biology and Health Cluster in the Division of Chemical, Bioengineering, Environmental, and Transport Systems.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.

器官是来自模仿人体器官结构和功能的干细胞产生的一组细胞。器官可用于建模人类疾病的发展和测试新生产的药物。但是，需要生成具有更好功能和较小变异性的人类器官。该项目旨在使用基于遗传的分析和工程来控制干细胞向人肝细胞的分化，并改善肝脏类器官的最终制造结果。作为该项目活动的一部分，将培训研究生和本科生，并为在线教育和公众参与而进行简短的教育视频片段。该研究项目将解决体外肝脏器官工程（例如成熟，血管形成和可重复性）的生物技术挑战。为此，将整合合成生物学，干细胞工程和系统生物学，以开发一个平台，以自主分化的人类诱导的多能干细胞与肝脏类器官。研究将在两个独立的目标中进行：1）开发用于肝脏器官多步分化的合成基因回路，并2）在分化过程中识别谱系可塑性调节剂以控制工程器官中的最终细胞命运。通过这项工作获得的理解将解决适用于细胞分化，人肝脏成熟和血管形成的知识差距。该项目还将通过围绕干细胞工程的新型在线教育和公共外展活动提供强大的STEM劳动力的支持。该奖励奖由系统和合成生物学集群共同资助了分子和细胞生物科学和工程生物科学和工程生物学和健康生物学和健康集群的分工，并在化学，生物工程，环境范围内宣传，并反映了nssssssssssss. theSforss。通过基金会的智力优点和更广泛的影响评估标准通过评估来支持。