Tuning Gene Expression in Mammalian Cells by Transcriptional and Post-transcriptional Control

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Cell-based therapies are the new technology of choice in biomedicine, and synthetic biology offers a rational design route towards engineered cells that sense in the human body and record and respond as required. In this project we will use synthetic biology rules to design and build modular genetic systems for programmable sensing in model lymphocyte cell lines. This will involve genome engineering to rewire GPCR-based biosensors to sense small molecules such as melatonin and serotonin, and in parallel using RNA-based detection to sense miRNAs that are the hallmarks of cancer. The project will involve the use of CRISPR and Golden Gate assembly systems to integrate multigene constructs into lymphocyte cell lines and testing the resulting cells in lab-based assays. Collaboration is planned between signalling modelling teams and cancer research experts who can assess cell performance in mouse models.