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

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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.