Unusual Metal Regulation—Single-Cell, Single-Molecule Levels

Peng Chen, Chemistry and Chemical Biology, is working to understand how metal regulation in the cell can be manipulated for preventive and therapeutic purposes. To do this, Chen is directing a unique research program that applies and develops advanced single-molecule single-cell approaches to interrogate and understand the mechanisms of bacterial metal regulation in vitro and in live cells.

Defining how cells regulate the uptake and efflux of transition metals such as Zn and Cu is a key component in elucidating cellular mechanisms of metal homeostasis. Bacterial model systems provide paradigms for understanding metal-responsive gene regulation.

In E. coli, the metalloregulator ZntR senses Zn excess and activates Zn efflux, while Zur senses Zn sufficiency and represses Zn uptake, to keep this essential metal at appropriate physiological levels in the cell. CueR, a homolog of ZntR, senses intracellular Cu to activate Cu efflux/detoxification genes to keep this toxic metal minimal.

Chen’s research has led to discoveries of first-of-their-kind mechanisms of Cu/Zn-responsive transcriptional regulation, but new questions have also emerged. He is further determining the mechanism that couples CueR/ZntR regulation to DNA mechanical tension and the mechanism of Zur’s biphasic unbinding kinetics from DNA, two novel phenomena.

Chen is providing fundamental knowledge about cell biology of metals, which can be used for identifying causes or developing preventions of diseases that involve similar regulation processes, as well as helping the development of biochemical strategies to manipulate bacterial Zn/Cu regulation to impair pathogen growth.

NIH Award Number: 2R01GM109993-05

Cornell Researchers

Funding Received

$1.1 Million spanning 4 years