BPCPPDYSOE21 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 6: Systems Biology I
BP 6.3: Vortrag
Montag, 22. März 2021, 11:40–12:00, BPc
Genetically engineered control of phenotypic structure in microbial colonies — •Philip Bittihn1,4, Andriy Didovyk1,5, Lev S. Tsimring1, and Jeff Hasty1,2,3 — 1BioCircuits Institute — 2Department of Bioengineering — 3Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA — 4Department of Living Matter Physics, Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany — 5Vertex Pharmaceuticals, San Diego, California, USA
Many essential biological behaviors originate from an entanglement of biological (cellular) and physical processes. This is a challenge not only for traditional biology and physics methodology, but also for synthetic biology, where such interactions severely limit the ability to engineer desired behavior with artificial gene regulatory networks. We show how to achieve control of phenotypic structure in bacterial microcolonies by simultaneously exploiting internal gene expression and metabolism, as well as physical coordination through nutrient diffusion and growth, which leads to self-generated nutrient gradients and a heterogeneous population consisting of both dividing and dormant cells. In microfluidic experiments and a mathematical model, we show that gene circuits which sense and control growth can create a spatio-temporal feedback loop via nutrient transport and generate sustained growth oscillations, while a phenotype-specific lysis circuit can selectively eliminate dormant cells. Our results demonstrate how to understand and control multicellular substrates as complex active physical systems.
Reference: Nature Microbiology 5, 697–705 (2020)