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From Synthetic Bacterial Adhesions to Synthetic Bacterial Materials

Sponsored by National Institute of General Medical Sciences

$622K Funding
1 People

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Engineering of bacterial synthetic multicellular systems and materials hold promise for many health-relevant applications such as modular drug biosynthesis living diagnostic devices and synthetic biolm researchmodels. To date bacterial synthetic biology has largely focused on the scales of molecules and single cells.Equivalent work on bacterial synthetic consortia is much less advanced in signicant part due to the previous lackof suitable synthetic and genetically encoded cell-cell adhesion tools to control the assembly development andfunctionality of multicellular systems. We recently developed the rst such synthetic cell-cell adhesion toolbox aswell as tools for optogenetically controlling cell-surface deposition and patterning. The specic objectives of this research are to signicantly advance these synthetic cell-adhesion tools andto develop design principles and predictive modeling tools that enable consortia engineering and patterning thatintegrate all relevant length scales (i.e. molecular cellular and multicellular) and ultimately pave the way formedially relevant applications. Our main hypothesis is that we can signicantly advance our control over thestrength specicity and subcellular localization of synthetic adhesion proteins in Escherichia coli which willallow rational tuning of consortium-level biophysical properties such as porosity and viscoelasticity and whichwill ultimately enable versatile multicellular consortium engineering and patterning. This work will constitutea foundation for various biomedical applications such as biocompatible materials multicellular plug-and-playpathway engineering targeted in-vivo drug delivery and living diagnostic devices. Our interdisciplinary methodology combines synthetic biology biophysics instrumentation and modeling. Allexperiments will be done in a quantitative manner. The proposed investigations include three independent yetsynergistic Specic Aims motivated by our hypothesis: (Aim 1) Advance the functionality of the synthetic adhesintoolkit at the subcellular level; (Aim 2) Achieve engineering control over synthetic consortium properties such asviscoelasticity and porosity at the scale of 10-100 m; and (Aim 3) Achieve higher-level consortium patterningon the scale of centimeters and demonstrate potential for medical applications. The PI (Prof. Riedel-Kruse) and his team are well-suited for this project as we have signicantexpertise in synthetic biology biophysics instrumentation (e.g. microuidics imaging) and modeling geneticcircuits and biophysical systems across scales. We developed the rst synthetic cell-cell and optogenetic cell-surfaceadhesion toolboxes in bacteria. Multiple collaborators provide additional domain expertise in key areas. Overallthis project's innovation lies in establishing synthetic adhesins as an essential and integral component of thesynthetic circuit-engineering toolbox and in establishing a novel paradigm for modular engineering of multicellularliving materials. Accordingly this project will broadly impact the engineering of synthetic consortia for basicresearch as well as enable a dynamic spectrum of future applications in health.