Co-evolution of small molecule responsive riboswitches

基因表达的小分子调控剂能够对基因表达进行快速、时空调控，在生物医学领域具有重要的应用价值。实际上，可用于一般用途的小分子诱导型表达系统的实例相对较少。此外，使用不同的小分子抑制剂或诱导剂同时差异控制多个基因表达的能力仍然非常有限。在这个项目中，我们的目标是设计新的调节系统，在原核和真核细胞中发挥作用，并以快速的剂量依赖性方式对广泛的小药物样分子作出反应。据设想，响应于广泛的小分子来控制基因表达的能力可以导致在药物靶标验证、基因治疗、生物修复、生物传感器和植物生物技术中的许多深远的应用。

Small molecule modulators of gene expression, which offer rapid, temporal and spatial control of gene expression, would be tremendously valuable tools in biological and biomedical sciences. Indeed there are relatively few examples of small molecule-inducible expression systems that are available for general use. In addition, the ability to control differentially the expression of multiple genes simultaneously, using distinct small molecule inhibitors or inducers, remains extremely limited. In this project we aim to engineer new regulatory systems that function in prokaryotic and eukaryotic cells and respond in a rapid dose-dependent fashion to a wide range of small drug-like molecules. It is envisaged that the ability to control gene expression in response to a wide range of small molecule could lead to many profound applications in pharmaceutical target validation, gene therapy, bioremediation, biosensors, and plant biotechnology.