Abstract

The Glycobiology Core will provide a resource for all Center members providing expertise and facilities in glycan/glycoprotein engineering and structural analysis of glycans. Approximately half of the molecular mass of HIV gp120 is comprised of N-linked glycans that shield the protein backbone. These glycans impact on vaccine design in three distinct ways. Firstly, the carbohydrates themselves are distinct from typical human glycosylation and can serve as a target for broadly neutralizing antibodies. Secondly, the glycans of gp120 limit or modulate antibody recognition of underlying protein epitopes. Finally, both viral (and immunogen) glycans can interact with host cell lectins and trigger major immunomodulatory signaling pathways. The Glycobiology Core is devoted to supporting Center members in the optimization of these critical parameters for vaccine design.

Public Health Relevance

The Glycobiology Core will contribute to the development of immunogens by the provision of a range of analytical tools (NP-HPLC, MALDI-MS, ESI-MS/MS and Ion Mobility MS) and provide full compositional and linkage information on viral and immunogen glycans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1AI100663-03
Application #
8681350
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Tsui, Carlson; Martinez-Martin, Nuria; Gaya, Mauro et al. (2018) Protein Kinase C-? Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis. Immunity 48:1144-1159.e5
Porichis, Filippos; Hart, Meghan G; Massa, Alexandra et al. (2018) Immune Checkpoint Blockade Restores HIV-Specific CD4 T Cell Help for NK Cells. J Immunol 201:971-981
Cao, Liwei; Diedrich, Jolene K; Ma, Yuanhui et al. (2018) Global site-specific analysis of glycoprotein N-glycan processing. Nat Protoc 13:1196-1212
Cheng, Hao D; Grimm, Sebastian K; Gilman, Morgan Sa et al. (2018) Fine epitope signature of antibody neutralization breadth at the HIV-1 envelope CD4-binding site. JCI Insight 3:
Sarkar, Anita; Bale, Shridhar; Behrens, Anna-Janina et al. (2018) Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer. Nat Commun 9:1956
Harvey, David J; Seabright, Gemma E; Vasiljevic, Snezana et al. (2018) Isomer Information from Ion Mobility Separation of High-Mannose Glycan Fragments. J Am Soc Mass Spectrom 29:972-988
Leipold, Michael D; Obermoser, Gerlinde; Fenwick, Craig et al. (2018) Comparison of CyTOF assays across sites: Results of a six-center pilot study. J Immunol Methods 453:37-43
Cohen, Yehuda Z; Lorenzi, Julio C C; Seaman, Michael S et al. (2018) Neutralizing Activity of Broadly Neutralizing Anti-HIV-1 Antibodies against Clade B Clinical Isolates Produced in Peripheral Blood Mononuclear Cells. J Virol 92:
Gaya, Mauro; Barral, Patricia; Burbage, Marianne et al. (2018) Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells. Cell 172:517-533.e20
Tsui, Carlson; Maldonado, Paula; Montaner, Beatriz et al. (2018) Dynamic reorganisation of intermediate filaments coordinates early B-cell activation. Life Sci Alliance 1:e201800060

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