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Microbial Multicellular Behaviors

The lab focuses on understanding multicellular bacterial behaviors, using biofilm formation and swarming as model systems. Bacterial biofilms are surface-associated bacterial communities that are held together by an extracellular matrix. Cells within these communities are highly tolerant to antibiotics and display strong phenotypic heterogeneity. By combining microscopy, molecular biology techniques, advanced data analysis, machine learning, and mathematical modeling, we study how bacteria form complex multicellular communities, how these communities function, and how these communities affect bacterial ecology.

Biofilms in Ecology and Evolution

Why do bacteria form biofilms? Bacteria that are bound in biofilms are highly resistant against antibiotics and other chemical insults of the environment, which is a clear evolutionary advantage of forming biofilms. Remarkably, the mechanisms underlying the biofilm-antibiotic interaction is poorly understood, and we are investigating unicellular and multicellular responses to antibiotics in biofilms [Diaz-Pascual et al. 2019].
Apart from providing protection against toxins, evolutionary advantages to biofilm formation are vague. However, we recently found the mechanisms underlying the most important selective advantage of making a biofilm: predation avoidance by bacteriophages. [Vidakovic, et al. 2018; Simmons, et al. 2018; Simmons et al. 2019]
We also recently discovered another reason for why bacteria may want to form biofilms: physical aspects of the biofilm life style strongly favor the evolution of simple social behaviors, such as the production of shared resources or "public goods" [Drescher, et al. 2014; Nadell, et al. 2013]. In addition, we are investigation social interactions in spatially structured biofilm communities [Dragos, et al. 2018; Nadell, et al. 2016].

Biofilm Dynamics: From Growth to Dispersal

What determines the biofilm architecture, and how do cells decide when they should disperse from biofilms? We recently developed novel imaging techniques that allow us to track all individual cells in biofilms, revealing beautiful internal cellular arrangements, and the different stages of biofilm growth. Drescher, et al. 2016]
We are now using these (and improved) imaging techniques to identify key cell-cell interactions in biofilms that determine the multicellular community growth [Hartmann, et al. 2019]. Based on this single-cell imaging, we also revealed how biofilms interact with fluid flow [Pearce, et al. 2019] and how biofilms respond to antibiotics [Diaz-Pascual, et al. 2019].
Cells need not stay in a biofilm forever. Yet it is unclear how cells reach a decision for when they should decide to disperse. We recently discovered that cells monitor a self-secreted quorum sensing signal, and the local nutrient concentration, to reach robust decisions about dispersal as a collective. [Singh, et al. 2017]

Biophysics of Collective Behaviors

What can we learn about collective bacterial behaviors from physics? Many aspects of bacterial interactions are inherently physical. Some examples: During biofilm growth, cells push and pull on each other, while being embedded in an elastic matrix. Understanding the molecular transport of nutrients and metabolites through the biofilm also relies on physics. Before bacteria form biofilms, their swimming motility creates fluid flows that lead to physical interactions with surfaces and other bacteria.
[Jeckel, et al. 2019; Drescher, et al. 2011; Wensink, et al. 2012; Dunkel, et al. 2014;]

Biofilm Interactions with Flow

How do biofilms grow in realistic physical and chemical environments? Biofilms are often thought to occur as surface-attached films. However, in environmental conditions that mimic their natural habitats, biofilms of P. aeruginosa and S. aureus are deformed into string-like structures. We discovered that these structures have a mesh-like architecture that captures other cells that are flowing past to grow explosively fast and cause rapid clogging of various industrial, environmental, and medical flow systems.
[Pearce, et al. 2019; Drescher, et al. 2013; Kim, et al. 2014]

Video describing our research

From The Blavatnik Awards on Vimeo.

Video describing the use of microfluidics for biofilm research