Protein Nanowires Lab

How do bacteria breathe in anoxic environments? Structures, functions, and electron transfer mechanisms of protein nanowires

Extracellular electron transfer via bacterial appendages, known as microbial nanowires, has long been studied in Geobacter and other bacteria due to these soil organisms’ crucial role in globally important environmental processes and their applications for bioremediation, bioenergy, biofuels, and bioelectronics. Since 2005, it had been thought that these nanowires are pili filaments in thousands of papers without direct evidence. Using cryo-electron microscopy, we found that nanowires are made up of polymerized cytochromes  (Cell 2019 & Nature Chem. Bio. 2020) wheras pili are involved in their secretion (Nature 2021).

The discovery of nanowires was nominated as Proteopedia’s  highest impact structures and was highlighted in New York Times. This work explains our prior discoveries of how bacteria use nanowires for interspecies electron transfer (Science 2010), and electricity production (Nature Nano 2011). Our work thus provides new insights into bacterial survival mechanisms to control their pathophysiology and ecology for an emerging field of electrogenetics. We are also establishing on-demand biomanufacturing of self-repairing, robust materials with tunable properties in living cells and networks using electrogenetics, synthetic biology and biomimetic peptides.

The members will work on one or more of the following three major research themes of our lab:

1) Biophysical mechanism of ultrafast electron transport: We are determining the mechanism underlying efficient transport of electrons, ions, spins and excitons in protein nanowires that occurs at ultrafast (<100 fs) rates and centimeter distances unprecedented in biomolecules. We have found a novel electron escape route in proteins to avoid oxidative damage (PNAS 2021).

2) Asembly of nanowire electron transport system.  We are identifying the nanowire biogenesis and secretion machinery using genetic tools combined with cryo-electron microscopy (Nature 2021) and tomography and reconstituting the machinery into new species.

3) Optimizing gut and lung microbiota composition through microbial electron transfer. We are developing a combination of prebiotics (electrons) and probiotics (wired bacteria) as a truly orthogonal dietary niche for reversible engraftment of commensals in diverse environments.

Projects involve structural studies, genetically engineering nanowire conductivity, nanoscale electron transfer measurements in nanowires and living biofilms,  spectroelectrochemistry as well as building and experimentally-testing computational models (with Victor Batista and Gary Brudvig, Yale Chemistry).