Evolveing the transcriptional regulatory system - towards synthetic control of gene expression

• Applicant: Dr. Patrick Sobetzko
• Subject Area: General Genetics and Functional Genome Biology ; Bioinformatics and Theoretical Biology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 419119108

With the advent of synthetic microbiology new challenges in Genetics arise. Minimal organisms, genetic circuit design, synthetic pathways and customized chromosomes all face a major bottleneck - the dependence of promoter activity and timing on its own sequence and context.The essence of synthetic approaches is the removal of a DNA segment from its native context. This has wide implications on the genes coded on this segment. Changes in the transcription of these genes may lead to a distortion of the linked regulatory or metabolic network.Therefore, the construction of complex synthetic circuits or pathways is currently not feasible.In this project we will further elucidate the impact of promoter sequence and the sequence context on promoter activity and timing to provide a better predictability of designed DNA and to further understand the governing rules of gene regulation.To accomplish this goal, we will combine Genetics and Bioinformatics approaches and apply state of the art approaches in Genomics, Transcriptomics and Synthetic Biology.We investigate positional effects on gene expression on three levels.1) The impact of promoter sequence and its direct context on temporal gene expression.2) The impact of chromosomal gene positioning on the gene regulatory network in the context of varying copy numbers during different growth stages. 3) The evolutionary reconstitution of a disturbed regulatory system. All levels will improve our general understanding of gene regulation and will provide new rules to design artificial constructs from single genes to full chromosomes.Furthermore, we are convinced that the data, gathered during the project, is of great interest for a broader scientific community.

• DFG Programme: Research Grants