Pattern Formation by Bacteria: from Theoretical Physics to Synthetic Biology – Bactterns

General Background:
How biological structures or patterns are formed is one of the most fundamental questions in modern science. It involves intriguing processes and has been a recurrent topic that fascinated generations of scientists. However, the underlying determinants are often buried in the overwhelmingly complex context so that a unified picture has yet to emerge.

Most approaches in the field are indeed limited to one specific viewpoint. Though our recent independent works on the pattern formation in bacterial colonies were well-received and published in major scientific journals (PNAS and Science), they are good examples of this limitation: the MSC partner proposed a novel putative mechanism of pattern formation in bacterial colonies, without being able to test it experimentally, while the HKU partner engineered bacteria that generate patterns using a similar mechanism, but could not fully characterize its microscopic physical origin.

A multi-disciplinary project:
It is our perception that further significant progress requires both linking the microscopic dynamics of individual cells to the macroscopic formation of biological structures, and accounting for the physical and biological aspects of cell motion and cell-cell interactions. The Bacttern project proposes to build such an integrative approach by combining theoretical and experimental physics—to model and characterize accurately biological pattern forming systems—and synthetic biology—which opens up the possibility to control cell behavior through the design of specific genetic circuits.

Core of the project:
We will focus on two experiments: the formation of circular patterns by the strains of Escherichia coli designed by the Hong-Kong partner, and the transition from mass swarming to mass sliding of Bacillus subtilis recently discovered in the MSC lab. These bacteria are indeed among the best-characterized cells: much is known about their genome, regulation, and cellular structure and functions. In addition, the genetic tools to design and assemble genetic circuits within them are mature. As such they form perfect model systems. Furthermore, these systems are largely complementary: first, the 3d swimming of E. coli in dilute suspensions strongly differs from the dense swarming of B. subtilis on the surface of agar plate; then, E. coli was designed to produce these patterns, using quorum-sensing systems to make the cell motility decrease with the local cell density, whereas the microscopic mechanisms inducing the swarming of B. subtilis are still under investigation. Last, the study of these systems will rely on the same experimental, theoretical and biological tools which make their common study particularly relevant.

Our study will follow two axes:
- We will bridge the gap between our past theoretical and experimental, physics-based and biology-based, approaches of pattern formation in bacteria colonies to understand and control the motility-induced pattern formation process of E. coli and B. subtilis.
- This will yield well-controlled pattern forming systems which can in turn be used to probe spatio-temporal phenomena in population dynamics. We will use these systems to study how the underlying bacteria-bacteria interactions, which affect the spatial distribution of the colonies, can lead to cell-sorting, interplay with genetic segregation, and affect the population dynamics of multi-species systems.

Consortium:
The successful completion of Bactterns will be possible thanks to the complementarity of the French and Hong-Kong teams, gathering in the same project expertise in experimental physics, mathematical modeling and synthetic biology. This synergy, much needed to make substantial progress in the field of bacterial pattern formation, will also strengthen both teams and countries on the long term, thanks to the technological transfer between the partners.