Design principles for synthetic gene regulation: understanding how cis-regulatory functions are encoded in plant DNA

植物正在成为与商业相关的高价值天然产品的生产系统。这需要一套非同源的、具有特征的调节元件来应用，例如平衡响应电路中的组件，防止有毒中间体沿着生物合成途径积聚。植物调控序列是由蛋白质结合基序和顺式调控元件组成的复杂排列。初级DNA序列和二级DNA结构都通过招募蛋白质和决定核小体结构来调节基因的表达。这个项目将应用一种原创的合成生物学方法来研究序列和功能之间的关系，利用比较基因组学方法来指导合成调控序列的设计。这将使我们能够理解顺式调控功能是如何在特定的DNA序列中编码的。该项目将专注于识别和表征在植物中保守的顺式调控元件，以便为设计跨物种发挥作用的最小合成元件提供信息。基因组序列的比较分析将被用来指导迭代的“设计-构建-测试-学习”循环，在这个循环中，将分析设计的、合成的序列的文库的功能。学生将接受生物信息学和比较基因组学分析、合成生物学方法以及低通量和高通量植物分子生物学和生物技术方面的培训。

Plants are emerging as commercially-relevant production systems for high-value natural products. This requires suites of non-homologous, characterised regulatory elements for applications such as balancing components within a responsive circuit and preventing the build-up of toxic intermediates along a biosynthesis pathway. Plant regulatory sequences are comprised of complex arrangements of protein binding motifs and cis-regulatory elements. Both the primary DNA sequence and secondary DNA structure contribute to regulating gene-expression by recruiting proteins and dictating nucleosome architecture. This project will apply an original synthetic-biology approach to study the relationship between sequence and function utilising comparative genomic approaches to inform the design of synthetic regulatory sequences. This will enable us to understand how cis-regulatory function is encoded in specific DNA sequences. The project will focus on the identification and characterisation of cis-regulatory elements conserved across plants to inform the design of minimal synthetic elements that function across species. Comparative analysis of genome sequences will be used to inform iterative 'design-build-test-learn' cycles in which the function of libraries of designed, synthetic sequences will be analysed. The student will be trained in bioinformatics and comparative genomics analyses, synthetic biology approaches and low and high-throughput plant molecular biology and biotechnology techniques.