Designing Synthetic Genetic Components for mRNA Therapeutics

该项目将涉及1）决定人类组织中蛋白质表达的潜在细胞类型特异性特征的生物信息学分析。例如编码序列特征、UTR特征、信号肽特征。2)使用1中的信息，学生将设计具有不同预测功能的合成mRNA序列库（例如，在肌肉细胞中的高水平表达，在树突细胞中的最小表达）。3)将在体外细胞模型中测试序列，以使用高通量筛选技术（例如使用机器人液体处理器等）评估它们的性能。4)在数据分析之后，将设计、合成和测试第二代序列。5)项目的主要产出是新的mRNA序列部分，具有确定和验证的功能，可纳入基因疗法/疫苗中，以提高产品性能（即提高表达量，减少副作用）。

The project will involve 1) bioinformatics analysis of potential cell-type specific features that determine protein expression in human tissues. E.g. coding sequence features, UTR features, signal peptide features. 2) Using information from 1, the student will then design libraries of synthetic mRNA sequences with varying predicted functions (e.g. high level expression in muscle cells, minimised expression in dendritic cells). 3) sequences will be tested in in vitro cell models to assess their performance using high-throughput screening techniques (e.g. using robot liquid handlers etc). 4) following data analysis, second generation sequences will be designed, synthesised and tested. 5) the major project outputs are new mRNA sequence parts with defined and validated function that can be incorporated into gene therapies/vaccines to enhance product performance (i.e. higher expression with reduced side-effects).