(35f) Understanding the Effects of Cooperation and Competition on Microbial Growth Pattern through Mathematical Modeling and Experiments (Faculty/Industry Candidate)

Most biological functions are performed by complex multicellular structures that act in perfect unison in a coordinated manner. These structures are formed from a few cells in the beginning, reproducing and responding to their extracellular environments. Hence, it is essential to understand the role of the factors affecting the formation of these structures. Relatively simpler microbial communities in well controlled experimental setups are suitable for studying this phenomenon of structure or pattern formation (Chen et al., 2014). Moreover, it has been seen that secretion of ‘public goods’ in systems such as the one used in this study leads to multicellularity itself (Koschwanez et al., 2013). In this work, we experimentally study how opposing strategies such as cooperation and competition lead to interesting microbial growth patterns and develop a mathematical model based on these observations that can help us understand the underlying dynamics and potentially, in future, help in making design choices that will lead to desirable pattern formations tailored to specific biotechnological applications. Budding yeast (also known as baker’s or brewer’s yeast), Saccharomyces cerevisiae hydrolyzes disaccharides such as sucrose into easier-to-metabolize monosaccharides such as glucose and fructose in the scarcity of extracellular glucose or fructose. This conversion is catalyzed by the enzyme invertase in the periplasmic space (area between the cell wall and plasma membrane) of the ‘producer’ cells. The greater part of the hydrolyzed monosaccharides diffuses away before being consumed by the cell that produces it, and ‘cheater’ cells (cells without the gene that produces the hydrolyzing enzyme invertase) in the same medium, can survive on this glucose and fructose. We study the growth of two such strains in a co-culture. An interesting growth dynamics arises in this reaction-diffusion system, from the production, diffusion and consumption of the monosaccharides. In this case, these strains have also been genetically modified to apply an additional diffusion gradient to the system that leads to competition between the two cell types. The presence of these two opposing interactions results in interesting growth patterns. This system is studied by manipulating aspects of the system that controls the availability of the limiting nutrients to the cells, such as, the initial population density, the initial ratio of producer and cheater cells and the initial concentrations of the limiting nutrients. A dynamic mathematical model is developed to simulate the multiple reaction-diffusion phenomena in the system. The concentration profiles of the limiting nutrients and the two cell types over the entire culture plate are tracked over time using a system of PDEs (partial differential equations). The model predicted growth patterns are compared with the experimental ones to calibrate the model. Then, the model is further used to predict the final pattern based on the initial conditions. It is also utilized to provide important insight into the growth dynamics of such microbial communities such as what kind of initial conditions lead to what regimes of growth and how multiple factors such as initial population density, initial ratio of the two types of cells and initial concentrations of limiting nutrients favor growth of one type of cell over the other and lead to different growth patterns.

References

Chen L, Noorbakhsh J, Adams RM, Samaniego-Evans J, Agollah G, Nevozhay D, et al. (2014) Two-Dimensionality of Yeast Colony Expansion Accompanied by Pattern Formation. PLoS Comput Biol 10(12): e1003979. https://doi.org/10.1371/journal.pcbi.1003979

Koschwanez, J. H., Foster, K. R. & Murray, A. W. (2013). Improved use of a public good selects for the evolution of undifferentiated multicellularity. eLife 2013; 2:e00367 DOI: 10.7554/eLife.00367