Interspecies interactions in spatially structured communities
Most bacteria live in spatially structured biofilms, which can consist of dozens of different species. Cells in these biofilms affect each other’s growth and activity through a dense network of interactions. To understand the properties of these biofilms, we thus need to characterize the relevant interactions and develop a quantitative framework to predict how they combine to affect the activity of all the cells in the biofilm. We use single-cell microscopy, image analysis, and mathematical modeling to help create a better understanding of the how interspecies interactions affect the functioning of microbial communities that affect the health of humans and the planet.
How do interspecies interactions affect antibiotic tolerance?
Chronic infections are a leading cause of death, yet we still lack effective treatment strategies. These infections are often caused by multispecies biofilms, and interactions between member species can significantly alter the tolerance of these biofilms to antibiotics, thus contributing to treatment failure. Our goal is to create a quantitative understanding of how interactions between two major pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, affects the antibiotic tolerance of such multispecies communities.
Project members: Giulia Bottacin
How do short-range interactions affect community diversity?
We previously showed that cells in multispecies biofilms interact only over a very short range (of a few cell lengths). As a result, cells do not interact with all other community members, but only with the subset found in their direct neighborhood. This can have important consequences for the dynamics of the community: it can shield cells from competitors, but also prevent them from interacting with mutualistic partners. We are using a combination of mathematical modeling and experiments with synthetic communities to study how these short-range interactions affect the dynamics, diversity, and spatial arrangement of multispecies communities.
Project members: Alessia Del Panta
Phenotypic variation in pathogenic bacteria
Cells in bacterial populations can show substantial variation in phenotypes even if they all share the same genotype. In spatially structured populations, cells create microscale gradients through the uptake and release of molecules. In turn, cells adapt their activity to the local microenvironment, thus creating spatial differences in cellular activities. Moreover, bistability and gene expression noise can create phenotypic differences even in the absence of environmental variation. Phenotypic variation can have important consequences: it can increase the resilience of populations to environmental changes or allow for interactions between phenotypically distinct subpopulations. We use a combination of single-cell microscopy, image analysis, and mathematical modeling to investigate the causes and consequences of such phenotypic variation in pathogenic bacteria.
Stay or go: cellular decision making during the biofilm lifecycle
Most bacteria alternate between two lifestyles: a motile planktonic phase, that allows for the colonization of new habitats, and a sessile biofilm phase, that provides protection from many stressors. Bacteria evolved a complex regulatory network to switch between these lifestyles, with cyclic-di-GMP acting as the master regulator. Working together with the labs of Urs Jenal and Knut Drescher, we can for the first time measure the dynamics of cyclic-di-GMP at high spatiotemporal resolution throughout the biofilm lifecycle. Using these tools, we aim to decipher how individual cells decide if and when to leave the biofilm phase.
Project members: Fabian Wyss
Division of labor in virulence gene expression during plant infections
Pathogenic bacteria have a large arsenal of virulence genes to suppress host immune response. However, the expression of these genes often comes at a large cost. Several pathogens thus evolved a division of labor where only a subset of cells expresses the virulence genes, allowing the others to proliferate at a fast rate. This process has been well studied in the context of human infections, but its role in plant infections is poorly understood. We are thus using single-cell imaging and mathematical to study the role of such a division of labor in the plant pathogen Xanthomonas.
Project members: Julien Luneau
Evolution of microbial communities
In the lab, the evolution of microbes is often studied in the context of isolated populations growing in relatively simple environments. However, most natural environments are much more complex: microbes live in spatially structured, multispecies biofilms where they strongly interact with many other species. Moreover, many microbes are associated with multicellular hosts, and these host strongly control the growth of their microbes. How do spatial structure, interspecies interactions, and host control affect the evolution of microbial communities? We are developing mathematical models to address these questions.
Project members: Simon van Vliet
Collaborations
We strongly believe that the best science emerges from interactions between a diversity of minds: we can only create a full understanding of complex systems by examining them from as many points-of-view as possible. We are therefore always very excited to collaborate with local and international partners, where we primarily contribute by assisting with single-cell imaging, image and data analysis, and mathematical modelling.
We have active collaborations with the groups of Urs Jenal (University of Basel), Alexander Harms (ETH Zurich), and Joanna Goldberg & Timothy Read (Emory University) where we assist with single-cell microfluidics. Moreover, we are collaborating with the group of Adria LeBoeuf (University of Fribourg) to develop a mathematical model to understand the evolution of metabolic division of labor in ants.