Research

A bacterial cell has long been thought of as a sack of protein soup – no organelles, no spatial organization. As a result, our ideas of how a cell can be organized have largely come from studying eukaryotic cells. Eukaryotes spatially organize their organelles and chromosomes using protein motors, like Kinesin and Dynein, that drive on highways made of actin filaments or microtubules.  


Recent advances in microscopy have shown that bacteria DO have organelles and subcellular organization. But bacteria don’t have linear motors that drive on protein highways. So how then does a bacterial cell spatially organize its essential process for life, like organelle trafficking, chromosome segregation, and cell division?


Cell-free reconstitution and imaging of self-organizing systems has fundamentally changed our understanding of how things get to where they need to go in the bacterial cell. We find that instead of driving on highways, bacterial components prefer another mode of travel. Surfing (see video)! We are excited to understand how both pathogenic and beneficial bacteria organize their cellular components using this surfing mechanism. For bacterial pathogens, understanding how to break the surfboard, can help us design new antibiotics.

Surfing surfaces – A model for transport in bacteria

ParA protein (green) binds the nucleoid and the ParB protein (red) binds the cargo. ParB releases ParA around the cargo, creating a ParA gradient. Replicated cargo segregate as they chase ParA in opposite directions. Animation by Ethan Tyler; Vecchiarelli et al., PNAS 2014


This ubiquitous mode of transport and positioning in bacteria is a new field of study with important implications in manipulating metabolism as well as identifying targets to combat antibiotic-resistant bacteria. We are interested in studying the systems and mechanisms responsible for subcellular organization in bacteria using genetics, biochemistry, and microfluidic approaches combined with cell and cell-free imaging. Two examples of surfing protein gradients in bacteria are below.


How do Bacteria Position Cell Division?

Inside the cell

Min Oscillation + FtsZAn oscillatory system positions cell division so that daughter cells are equal in size. Wu et al., Front Microbiol 2015

Outside the Cell

On a flat bilayer, the spatial regulators of cell division form a variety of patterns. Dissecting how these patterns form outside of the cell is unraveling the oscillatory mechanism used inside the cell. Vecchiarelli et al., PNAS 2016


How do Bacteria Segregate DNA?

Inside the Cell

pb171-2A plasmid is segregated in E.coli, using the nucleoid as a track. Ringgaard et al., PNAS 2009

Outside the Cell

A plasmid segregation system is used to transport a bead on a nucleoid biomimetic. Vecchiarelli et al., PNAS 2014

Simulations

Simulations of a bead transported by a protein gradient on a surface. Vecchiarelli et al., BioArchitecture 2014