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. Interactions between peptide residues and cations, such as that between Zn+2 and the zinc finger (ZnF) motifs, are vital constituents of cellular communication. The proposed investigation is relevant to the mission of Nebraska's INBRE program in that it will advance knowledge in the area of cell-signaling affected by interactions with zinc. Developing new sensor systems based on ZnF motifs will allow direct measurement of how zinc affinity varies with peptide identity and permit direct measurements to be made regarding the binding affinities of toxic metal ions relative to Zn+2 for a prescribed set of peptide chelating motifs. Such studies will lead to new insights as to how ZnF's exert selectivity for zinc and how toxic metals might lead to cellular damage. While using a synthetic chemical approach to better understand nature, this project will also exploit nature to develop new tools for ion and small molecule sensing, as the molecules developed for these studies will stand as new sensors for zinc detection. This study's first generation systems will be based on well-known ZnF chelator-analyte interactions (CCHH ZnF motif with Zn+2) in order to facilitate efficient structural optimization of the system's fluorescent output. Once optimized, point-mutation studies will be performed by modulating amino acid residue identities with the goal of discovering new derivatives selective for varying analytes. Uniquely, the proposed sensors have been designed to also allow the wavelength of arene fluorescence output to be modified independently of peptide variations, promising the ability to engineer multicolor readouts for varying analytes within a single chemosensor design. Because amino acid residues serve as the analyte recognition units in these systems, any analytes capable of noncovalently interacting with peptides could potentially be targeted using this general molecular approach (including cations, anions and small organic molecules). Hence, discoveries made in the proposed investigation will not only advance the understanding zinc's role in cellular communication but will also impact the field of fluorescence chemosensing.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016469-11
Application #
8360026
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
11
Fiscal Year
2011
Total Cost
$34,956
Indirect Cost
Name
University of Nebraska Medical Center
Department
Genetics
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Gerald, Gary W; Thompson, Moriah M; Levine, Todd D et al. (2017) Interactive effects of leg autotomy and incline on locomotor performance and kinematics of the cellar spider, Pholcus manueli. Ecol Evol 7:6729-6735
Gong, Qiang; Wang, Chao; Zhang, Weiwei et al. (2017) Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data. Sci Rep 7:11301
Bouska, A; Zhang, W; Gong, Q et al. (2017) Combined copy number and mutation analysis identifies oncogenic pathways associated with transformation of follicular lymphoma. Leukemia 31:83-91
Lu, Guoqing; Luhr, Jamie; Stoecklein, Andrew et al. (2017) Complete Genome Sequences of Pseudomonas fluorescens Bacteriophages Isolated from Freshwater Samples in Omaha, Nebraska. Genome Announc 5:
Azadmanesh, Jahaun; Trickel, Scott R; Borgstahl, Gloria E O (2017) Substrate-analog binding and electrostatic surfaces of human manganese superoxide dismutase. J Struct Biol 199:68-75
Donze-Reiner, Teresa; Palmer, Nathan A; Scully, Erin D et al. (2017) Transcriptional analysis of defense mechanisms in upland tetraploid switchgrass to greenbugs. BMC Plant Biol 17:46
Quispe, Cristian F; Esmael, Ahmed; Sonderman, Olivia et al. (2017) Characterization of a new chlorovirus type with permissive and non-permissive features on phylogenetically related algal strains. Virology 500:103-113
Carlson, Kimberly A; Zhang, Chi; Harshman, Lawrence G (2016) A dataset for assessing temporal changes in gene expression during the aging process of adult Drosophila melanogaster. Data Brief 7:1652-7
Tietze, S M; Gerald, G W (2016) Trade-offs between salinity preference and antipredator behaviour in the euryhaline sailfin molly Poecilia latipinna. J Fish Biol 88:1918-31
Ericson, Brad L; Carlson, Darby J; Carlson, Kimberly A (2016) Characterization of Nora Virus Structural Proteins via Western Blot Analysis. Scientifica (Cairo) 2016:9067848

Showing the most recent 10 out of 316 publications