We study the cell biology of bacteria, whose awesome experimental power allows us to attack questions with an integrated combination of genetics, biochemistry, microscopy, genomics, quantitative analysis, and computation. Our interdisciplary efforts are aided by our wonderful group of Princeton friends and collaborators.

Our current efforts are focused on three main areas/questions:

Self-organization and Growth: How do organisms like bacteria make such amazing and complex structures out of such simple building blocks? Our lab has discovered fundamental mechanisms by which self-assembly happens across a wide range of spatial scales, from atoms and metabolites to proteins and polymers to cells and communities. For example, by assembling nanometer-sized proteins into micron-sized cytoskeletal polymers, bacteria make the measurements necessary to achieve their characteristic shapes. And by modulating ribosomes in different ways bacteria can achieve similar growth rates in different nutrient conditions. We are now working on the mechanisms by which self-assembly occurs as well as its functions in cell shape, metabolism, and pathogenesis and investigating growth from both surface area and biomass perspectives.

Microbe-host interactions: Once built, how do those bacteria interact with each other, their hosts, and their environments? Our lab discovered that pathogens like P. aeruginosa use mechanosensing to sense the presence of host cells and induce virulence pathways. Meanwhile, hosts can sense the presence of specific bacterial species based on their sRNA sequences. We are now focusing on novel mechanisms and functions of these and other forms of microbe-host interactions.

Antibiotics: How can we use our quantitative tools to both discover and characterize novel antibiotics? The rise of antibiotic resistance has made the discovery of novel antibiotics an urgent societal threat, yet the pipeline of truly novel antibiotics has largely dried up. We have used a combination of imaging, machine learning, and systems approaches to develop new approaches to rapidly determining antibiotic mechanisms of action. We used these methods to discover one of the first novel antibiotics to be found in decades. We are now focusing on understanding how these novel antibiotics function, discovering additional novel antibiotics, and using antibiotics to probe previously unappreciated features of bacterial cell biology. We are also working on ways of reducing the emergence of antibiotics resistance using anti-virulence and multi-targeting approaches.

Learn more about our research