We propose to continue the COBRE on Membrane Protein Production and Characterization at the University of Delaware as a Phase III COBRE infrastructure center. The critical role of membrane proteins in biology is clearly reflected in the fact that they represent >30% of the human genome and are the targets of >50% of all therapeutics on the market today. Nevertheless, significant challenges remain in producing and characterizing them, especially within the realm of structural biology. Consequently the objectives of research in the COBRE will be to express, solubilize, purify and crystallize membrane proteins;to determine their structures;and to characterize their functions at the molecular level and in larger biological systems in both health and disease. These objectives are congruent with those of the Structural Biology component of the NIH Roadmap and the Protein Structure Initiative in addressing an area of critical importance for biomedical research. The infrastructure center will complement research in the laboratories of an interdisciplinary group of more than a dozen PIs, whose work is independently supported. To this end the center will include: research and instrumentation cores (Protein Expression and Biophysical Characterization;Structural Biology;and a group of Core Facilities co-funded with, among others, the Delaware INBRE);continuation of the current pilot research subproject program;a predoctoral training program modeled on the NIH T32 mechanism;and continuation of the existing annual symposium series. The administration of the center will be guided by an internal Steering Committee and will continue to benefit from the input of an External Advisory Committee, including for review of pilot project proposals. The research within the COBRE coupled with the capabilities provided by the infrastructure center will continue to give the University of Delaware distinctive strength in an area of research critical to biology and biomedicine.

Public Health Relevance

Membrane proteins exist in the membrane surrounding each cell and are critical to cellular growth, communication and nutrition, yet how these proteins function is still relatively poorly understood. The purpose of this center is to provide infrastructure for research to develop improved methods to produce and study membrane proteins, which can yield major benefits for basic biology and drug development.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Center Core Grants (P30)
Project #
5P30GM103519-04
Application #
8528632
Study Section
Special Emphasis Panel (ZRR1-RI-2 (01))
Program Officer
Taylor, Fred
Project Start
2010-09-10
Project End
2015-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$1,079,524
Indirect Cost
$373,953
Name
University of Delaware
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716
Angelo, James M; Cvetkovic, Aleksandar; Gantier, Rene et al. (2016) Characterization of cross-linked cellulosic ion-exchange adsorbents: 2. Protein sorption and transport. J Chromatogr A 1438:100-12
Zhang, Huilan; Hou, Guangjin; Lu, Manman et al. (2016) HIV-1 Capsid Function is Regulated by Dynamics: Quantitative Atomic-Resolution Insights by Integrating Magic-Angle-Spinning NMR, QM/MM, and MD. J Am Chem Soc :
Bhambure, Rahul; Gillespie, Christopher M; Phillips, Michael et al. (2016) Ionic strength-dependent changes in tentacular ion exchangers with variable ligand density. I. Structural properties. J Chromatogr A 1463:90-101
Freudenberg, Uwe; Liang, Yingkai; Kiick, Kristi L et al. (2016) Glycosaminoglycan-Based Biohybrid Hydrogels: A Sweet and Smart Choice for Multifunctional Biomaterials. Adv Mater 28:8861-8891
L Black, Kathryn; Petruk, Svetlana; Fenstermaker, Tyler K et al. (2016) Chromatin proteins and RNA are associated with DNA during all phases of mitosis. Cell Discov 2:16038
Naranjo, Andrea N; McNeely, Patrick M; Katsaras, John et al. (2016) Impact of purification conditions and history on A2A adenosine receptor activity: The role of CHAPS and lipids. Protein Expr Purif 124:62-7
Angelo, James M; Lenhoff, Abraham M (2016) Determinants of protein elution rates from preparative ion-exchange adsorbents. J Chromatogr A 1440:94-104
Maresca, Julia A; Keffer, Jessica L; Miller, Kelsey J (2016) Biochemical Analysis of Microbial Rhodopsins. Curr Protoc Microbiol 41:1F.4.1-1F.4.18
Keffer, J L; Hahn, M W; Maresca, J A (2015) Characterization of an Unconventional Rhodopsin from the Freshwater Actinobacterium Rhodoluna lacicola. J Bacteriol 197:2704-12
Naranjo, Andrea N; Chevalier, Amy; Cousins, Gregory D et al. (2015) Conserved disulfide bond is not essential for the adenosine A2A receptor: Extracellular cysteines influence receptor distribution within the cell and ligand-binding recognition. Biochim Biophys Acta 1848:603-14

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