Cellular Communities

Naturally occuring populations of cells, whether genetically identical or composed of multiple species or strains, typically exhibit a wide range of phenotypic diversity. We aim to combine experimental and theoretical methods to understand the collective dynamical behaviour of such populations; for example: competition and cooperation in bacterial biofilms, periodic waves of growth and quiescence in yeast populations, the coevolution of viruses and bacterial defenses, and the evolution of multicellularity and hybrid cellular species.

Heterogeneity in genetically identical populations of cells

Populations of cells, even when they are all genetically identical, are often very heterogeneous with individual cells displaying widely varying phenotypic characteristics. This happens because genetically identical cells can be in different "epigentic" states. For instance, even a well-mixed bacterial colony will typically contain some "persisters" which are in a dormant, non-growing state that is relatively immune to antibiotic stress. Yeast cells growing in a chemostat appear to exhibit similar bistability with one sub-population consisting of growing cells, while the rest are non-growing, but these numbers change over time and indicate an intricate regulation of these states based on cell-cell communication. In more complex settings, such as biofilms, different sub-populations may take on different tasks that are all required for proper biofilm functioning, not unlike tissues in multicellular organisms. A group of theorists and experimentalists, connected via the Simons centre, are exploring a range of such phenomena. Current projects include: waves of growth and death in yeast populations, the role of non-coding RNA regulation in bacterial biofilm formation, the lysis-lysogeny decision in temperate phage.

Competition and cooperation in multispecies communities

Another level of complexity arises in ecosystems containing multiple different species or strains, which compete or cooperate with each other. An example of cooperation involves P. aeruginosa bacteria growing on milk. The cooperating bacteria produce an exoenzyme that breaks down casein in milk into small polypeptides that all the bacteria can ingest and metabolize. This raises a number of interesting questions that we are studying: How is such cooperation regulated? Does it make sense for bacteria to turn on and off cooperation depending on the situation (e.g. depending on how many bacteria there are)? How can such cooperation survive in the presence of cheats, i.e. mutants or other species that take advantage of food generated by the cooperating bacteria but don't spend the energy required to make the exoenzyme? Competitive interactions also abound in microbial ecosystems, with examples ranging from virus-bacteria and protist-bacteria predator-prey interactions to inter-species bacterial warfare. Current projects in this area include studies of the coevolution of viruses and bacterial defenses, determinants of diversity in virus-bacteria ecosystems, the evolution of multicellularity and hybrid species.

Mechanisms of information transfer between cell/organisms

The phenomena outlined in the two sections above necessarily involve the transfer of information between individual cells, sometimes within a species and sometimes between species. The cooperating P. aeruginosa mentioned above must exchange information that allows each to estimate the density of bacteria. Viruses that infect bacteria often use information about the average ratio of viruses to bacteria to decide whether to stay dormant inside the bacterium or to kill it and produce a large burst of offspring. Such information is typically encoded chemically. For instance, most bacteria have "quorum sensing" systems consisting of small signaling molecules that they secrete into the environment, which can be used to measure the density of bacteria as well as aspects of the geometry and diffusion or flow properties of the surroundings. We study both the dynamics and design of known information transfer mechanisms, and also propose mechanisms where they are as yet unknown. Currently we are studying questions such as: what kinds of information would be useful for a virus to decide whether to stay dormant or kill a bacterium? how do quorum sensing systems integrate multiple pieces of information required to regulate production of public goods? how much and what kind of information would be optimal to exchange with a "partner" organism in order to reach a target genome through recombination?

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