Designing Synthetic Genetic Components for mRNA Therapeutics

该项目将涉及1)对决定人体组织中蛋白质表达的潜在细胞类型特定特征的生物信息学分析。例如编码序列特征、非编码区特征、信号肽特征。2)使用1中的信息，然后学生将设计具有不同预测功能的合成mRNA序列的库(例如，在肌肉细胞中的高水平表达，在树突状细胞中的最低表达)。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机等)评估其性能。4)在数据分析之后，将对第二代序列进行设计、综合和测试。5)主要项目的产出是新的具有明确和有效功能的信使核糖核酸序列部分，可纳入基因疗法/疫苗以提高产品性能(即更高的表达和更少的副作用)。

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).