Abstract

Studying gene regulatory networks in situ is very challenging, due to their embedding in large and complex cellular networks. Synthetic biology offers a path forward. Synthetically recapitulating biological processes and interactions provides a bottom-up approach towards understanding the general principles of their mechanisms and evolution. By extracting a gene regulatory network from its native cellular environment, it becomes feasible to systematically study the effects of mutations on the phenotype of a gene regulatory network. In my talk I will first show how we engineered synthetic gene regulatory networks in Escherichia coli to produce spatiotemporal patterns such as oscillations and stripes [1,2]. I will then present how we used these synthetic circuits to study how the mechanisms of gene regulatory networks constrain evolution [3], to perform a systematic analysis of epistasis [4] and to exemplify how the robustness of gene regulatory networks might be driving the evolutionary innovation [5].

1) A unified design space of synthetic stripe-forming networks, (2014) Nat. Commun., 5:4905

2) Multistable and dynamic CRISP Ri-based synthetic circuits, (2020) Nat. Commun., 11:2746

3) Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution, (2018) Molecular Systems Biology, 14:e8102

4) Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks, (2023) Sci. Adv., 9:eadf1773

5) Robustness and innovation in synthetic genotype networks, (2023) Nat. Commun., 14:2454