This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The Chivers lab is interested in how cells control intracellular levels of essential trace metals. A balance must be achieved between levels that are sufficient for growth and those that are toxic to the cell. They focus on the regulation and intracellular trafficking of nickel in microbes, in particular Escherichia coli and Helicobacter pylori. In these bacteria, nickel-enzymes are synthesized with the help of specific nickel-binding chaperones. The nickel-dependent transcriptional regulator NikR binds free nickel ions and represses expression of nickel uptake genes. NikR has also been shown to postively regulate gene expression of at least one operon (urrease) in H. pylori. The function of NikR indicates that free nickel ions accumulate only after sufficient nickel has been acquired to synthesize nickel-dependent enzymes. The high-affinity of NikR for nickel ions, however, suggests that nickel-trafficking pathways must actively compete with NikR for newly acquired nickel ions. A goal is to study the mechanism by which this partitioning is achieved. Our approach combines biochemical and biophysical studies of purified proteins (for example, fluorescence and UV-visible spectroscopy) with in vivo studies of protein function (molecular genetics, reporter assays) to correlate molecular properties, such as ligand-binding affinity, with biological function. A new direction is to use mass spectrometry, especially some of the biophysical approaches developed in the Michael Gross lab.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-34
Application #
8361350
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2011-01-01
Project End
2011-12-31
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
34
Fiscal Year
2011
Total Cost
$5,405
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Yue, Xuyi; Dhavale, Dhruva D; Li, Junfeng et al. (2018) Design, synthesis, and in vitro evaluation of quinolinyl analogues for ?-synuclein aggregation. Bioorg Med Chem Lett 28:1011-1019
Ohlemacher, Shannon I; Giblin, Daryl E; d'Avignon, D André et al. (2017) Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria. J Clin Invest 127:4018-4030
Lin, Xiaobo; Racette, Susan B; Ma, Lina et al. (2017) Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol 37:2364-2369
Ovod, Vitaliy; Ramsey, Kara N; Mawuenyega, Kwasi G et al. (2017) Amyloid ? concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841-849
Cade, W Todd; Levy, Philip T; Tinius, Rachel A et al. (2017) Markers of maternal and infant metabolism are associated with ventricular dysfunction in infants of obese women with type 2 diabetes. Pediatr Res 82:768-775
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2017) Associations Between ?-Amyloid Kinetics and the ?-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol 74:207-215
Alvarez, Jessica A; Ziegler, Thomas R; Millson, Erin C et al. (2016) Body composition and lung function in cystic fibrosis and their association with adiposity and normal-weight obesity. Nutrition 32:447-52
Sterl, Karin; Wang, Songyan; Oestricker, Lauren et al. (2016) Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery. Peptides 82:76-84
Wei, Xiaochao; Song, Haowei; Yin, Li et al. (2016) Fatty acid synthesis configures the plasma membrane for inflammation in diabetes. Nature 539:294-298
Shields-Cutler, Robin R; Crowley, Jan R; Miller, Connelly D et al. (2016) Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine. J Biol Chem 291:25901-25910

Showing the most recent 10 out of 696 publications