Chivers Lab Washington University in St. Louis - Department of Biochemistry and Molecular Biophyiscs

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Research Topics Research in the Chivers lab explores the relationship between protein structure and function to understand how these fascinating molecules carry out their diverse biological activities. Various experimental methods are used to understand relationships between protein structure and function to address biological questions in a physiological context. Our primary focus is on proteins involved in the regulation of intracellular nickel levels in bacteria. Trace metal acquisition is essential in all organisms. However, a balance must be achieved between the levels necessary to support growth and levels that are toxic to the cell.  The setpoint for each metal is determined by the physiology of the cell, which is dependent upon growth conditions and therefore exhibits dynamic behavior as the composition of the growth medium changes. The nickel requirement of many bacteria is usually quite high, roughly 1000-10000 fold higher than environmental concentrations (low nM). NikR NikR is nickel-dependent transcriptional regulator found in bacteria and archaea. It is a member of the ribbon-helix-helix family of DNA-binding proteins. The affinity of NikR for DNA is highest in the presence of nickel ions.  The structural basis by which nickel activates NikR for repression is currently under investigation. RcnR RcnR is a founding member of a distinct and recently identified structural class of transcriptional regulators.  RcnR regulates expression of a nickel-efflux protein, RcnA, in a nickel dependent manner.  We are studying how RcnR activity is regulated by nickel, how the function of RcnR and NikR are related within the cell, and how this new class of DNA-binding proteins interacts with DNA. We are also interested in the partitioning of nickel ions inside the cell, in particular the apparent competition for nickel ions between NikR, RcnR, and other nickel-binding proteins in the cell (nickel enzymes and chaperones).