This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Transcript levels for various enzymes and proteins involved in human glycoprotein biosynthesis, ER-associated glycoprotein disposal (ERAD), and unfolded protein response (UPR) will be quantitated by qRT-PCR. A set of projects are being initiated in collaboration with Dr. Hung Do (Amicus Therapeutics) to examine the roles of individual genes in ER quality control and glycoprotein degradation in human cells. Amicus Therapeutics is a biotech company developing small molecule chemical chaperone therapeutics for treatment of lysosomal storage diseases. These diseases are characterized by the accumulation of misfolded lysosomal enzymes in the ER of human cells where they potentially induce an unfolded protein response. We will employ patient-derived lysosomal storage disease cell lines as a model system to examine the effects of treatment with chemical chaperones or perturbation of the machinery involved in ER-associated degradation (by over-expression or shRNA knockdown). The effects of these treatments on lysosomal enzyme folding, maturation, and transport versus enzyme degradation will be examined in one set of studies while another set of studies will examine the effects of these treatments on transcript levels of the full set of glycan-related genes as well as genes involved in ERAD and UPR. These studies should reveal the interplay between misfolded glycoprotein biosynthesis, cellular glycosylation, ER degradation machinery, and machinery of the unfolded protein response.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR018502-05
Application #
7602809
Study Section
Special Emphasis Panel (ZRG1-BECM (40))
Project Start
2007-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
5
Fiscal Year
2007
Total Cost
$2,470
Indirect Cost
Name
University of Georgia
Department
Type
Organized Research Units
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Gas-Pascual, Elisabet; Ichikawa, Hiroshi Travis; Sheikh, Mohammed Osman et al. (2018) CRISPR/Cas9 and glycomics tools for Toxoplasma glycobiology. J Biol Chem :
Sheikh, M Osman; Thieker, David; Chalmers, Gordon et al. (2017) O2 sensing-associated glycosylation exposes the F-box-combining site of the Dictyostelium Skp1 subunit in E3 ubiquitin ligases. J Biol Chem 292:18897-18915
Ma, Liang; Chen, Zehua; Huang, Da Wei et al. (2016) Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts. Nat Commun 7:10740
Karumbaiah, Lohitash; Enam, Syed Faaiz; Brown, Ashley C et al. (2015) Chondroitin Sulfate Glycosaminoglycan Hydrogels Create Endogenous Niches for Neural Stem Cells. Bioconjug Chem 26:2336-49
Li, Juan; Murtaugh, Michael P (2015) Functional analysis of porcine reproductive and respiratory syndrome virus N-glycans in infection of permissive cells. Virology 477:82-8
DePaoli-Roach, Anna A; Contreras, Christopher J; Segvich, Dyann M et al. (2015) Glycogen phosphomonoester distribution in mouse models of the progressive myoclonic epilepsy, Lafora disease. J Biol Chem 290:841-50
Dwyer, Chrissa A; Katoh, Toshihiko; Tiemeyer, Michael et al. (2015) Neurons and glia modify receptor protein-tyrosine phosphatase ? (RPTP?)/phosphacan with cell-specific O-mannosyl glycans in the developing brain. J Biol Chem 290:10256-73
Li, Juan; Tao, Shujuan; Orlando, Ron et al. (2015) N-glycosylation profiling of porcine reproductive and respiratory syndrome virus envelope glycoprotein 5. Virology 478:86-98
Panin, Vladislav M; Wells, Lance (2014) Protein O-mannosylation in metazoan organisms. Curr Protoc Protein Sci 75:Unit 12.12.
Ingale, Jidnyasa; Tran, Karen; Kong, Leopold et al. (2014) Hyperglycosylated stable core immunogens designed to present the CD4 binding site are preferentially recognized by broadly neutralizing antibodies. J Virol 88:14002-16

Showing the most recent 10 out of 104 publications