Synthetic gene regulatory networks for pattern formation
During embryonic development, cells acquire different identities, depending on their spatial positions. This developmental process is called pattern formation. The molecular details of pattern formation are complicated, but are thought to be governed by general principles such as the use of morphogen gradients to provide positional information. We build, study and model synthetic gene regulatory networks to improve our understanding of such general principles.
Santos-Moreno, J., Schaerli, Y. (2018) Using Synthetic Biology to Engineer Spatial Patterns, Advanced Biosystems, doi: 10.1093/nar/gkv1310
Schaerli, Y., Munteanu, A.Gili, M.Cotterell, J.Sharpe, J.Isalan, M. (2014) A unified design space of synthetic stripe-forming networks, Nat. Commun., 5:4905
Perez-Carrasco, R., Barnes, C. P., Schaerli, Y., Isalan, M., Briscoe, J., Page, K. M. (2018) Combining a toggle switch and a repressilator within the AC-DC circuit generates distinct dynamical behaviors, Cell Systems, 6:1-10
Evolution of gene regulatory networks
What constrains the evolution of gene regulatory networks? What makes a gene regulatory network robust to mutations and/or evolvable? How does the regulatory mechanism of a network influence its evolution? How can gene regulatory networks change extensively, while maintaining overall circuit output? How do mutations in gene regulatory networks interact to produce novel phenotypes? What happens after a gene has been duplicated?
We have several ongoing projects where we address such questions by performing molecular evolution experiments with synthetic gene regulatory networks in E. coli.
One of the project is funded by a SNSF project grant.
Schaerli, Y., Jimenez, A., Duarte, J. M., Mihajlovic, L., Renggli, J., Isalan, M., Sharpe, J., Wagner, A. (2018) Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution, Molecular Systems Biology, 14:e8102
Duarte, J. M., Barbier, I., Schaerli, Y. (2017) Bacterial microcolonies in gel beads for high-throughput screening of libraries in synthetic biology, ACS Synthetic biology, doi: 10.1021/acssynbio.7b00111
Schaerli, Y., Isalan, M. (2013) Building synthetic gene circuits from combinatorial libraries: screening and selection strategies, Mol. BioSyst., 9:1559-1567