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

基于细胞的疗法是生物医学中的新技术选择，合成生物学为工程细胞提供了一条合理的设计路线，这些细胞可以在人体内感应，并根据需要记录和反应。在这个项目中，我们将使用合成生物学规则来设计和构建模块化遗传系统，用于在模型淋巴细胞系中进行可编程传感。这将涉及基因组工程，以重新连接基于GPCR的生物传感器，以检测褪黑激素和5-羟色胺等小分子，同时使用基于RNA的检测来检测作为癌症标志的miRNAs。该项目将使用CRISPR和Golden Gate组装系统将多基因构建整合到淋巴细胞系中，并在实验室测试得到的细胞。信号建模团队和癌症研究专家计划进行合作，他们可以评估小鼠模型中的细胞性能。

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.