Ron Weiss

EBICS Leadership Title: Research Director

Academic Title-Position: Professor of Biological Engineering

Department: Biological Engineering

University: Massachusetts Institute of Technology 

Research Lab: Weiss Lab for Synthetic Biology

Research Group Member: Organoids

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Current Research

Topic: Organoids

Contributing Trainee(s) and corresponding trainee projects: 

Graduate students:  Sebastian Palacios – “RNAi-based logic circuit engineering in hiPSCs,” Farimah Mapar – “Engineering of a neuronal toggle switch”. Postdoctoral researchers: Erez Pery – “3D Liver organoid formation and maturation,” Elvira Vitu – “Embedded synthetic biology for multistep organoid differentiation.”

Current technology for organoid and tissue engineering generally involves exposing a population of hiPSCs to chemical, mechanical or molecular signals that cause a response in the endogenous gene regulatory networks that control tissue formation. In many cases, these signals are the same that are observed during embryogenesis. Although appropriate in many cases to study development, this approach can exhibit significant challenges with reproducibility, control of cell fate, maturation, and custom tissue design. We develop engineering tools to precisely probe and control tissue formation. We focus on using the principles of synthetic biology to engineer synthetic gene regulatory networks that can precisely control tissue formation and the emergence of multicellular phenotypes. We develop these tools within a computational and engineering framework in the context of practical applications for Multi-Cellular Engineered Living Systems (M-CELS).

Figure 1. Biological devices for sensing and computation based on RNAi-based. (A) CRISPR/Cas9 technology was used to knockin an RMCE landing pad in the AAVS1 locus of hiPSCs. Engineered miRNA sensors were subsequently integrated into the landing pad. FACS data shows that the engineered miRNA sensor in AAVS1 locus can detect a miRNA that is transiently delivered into the cells. (B) Cells before transient delivery of the miRNA, and (C) three days after transient delivery of the miRNA. (D) hiPSCs with stable integration of miRNA sensors for miRNA FF4 and endogenous miRNA 25-3p, which is highly active in hiPCS. 

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