The Protein Chemistry Laboratory Core (PCLC) will serve as the major protein preparation and analysis resource for the Program Project. The laboratory will be responsible for protein preparation, characterization and identification, which will include project-driven proteomics. The PCLC is equipped with a peptide synthesizer, a lyophilizer, and various fast protein liquid chromatography (FPLC), high-performance LC (HPLC) and ultra-performance LC (UPLC) systems encompassing both micro and macro scales. Most importantly, the laboratory has a """"""""proteomics-appropriate"""""""" mass spectrometry (MS) system equipped with ionization modes that will enable sub-picomole analysis of proteins, peptides, and post-translational modifications (PTM) with bio-informatics support. All protein and peptide products will be subjected to stringent characterization by mass spectrometric/proteomic analysis. Surface plasmon resonance (Biacore) analysis is also available that is adaptable to coupling with the on-site mass spectrometers. The primary services provided will be the provision of protein-related tools and reagents such as purified complement system proteins, antibodies, synthetic peptides, and peptide-like synthetic antagonists that interrupt various and specific complement system protein-protein interactions. In addition, the PCLC will perform MS-based analyses of these reagents along with comprehensive sample analysis and high-throughput screening of PTM related to complement/inflammatory processes. All members of the Program Project will be served by the PCLC.

Public Health Relevance

The Protein Chemistry Laboratory Core (PCLC) will provide all of the projects of this proposal with protein and peptide reagents, including proteins and inhibitors of the complement system, an important part of innate immunity. The PCLC will characterize these products to ensure purity and quality and analyze experimental samples from the various projects through mass spectrometric analyses. These activities of the PCLC are vital for each of the projects to ensure efficient, reliable, and cost-effective research.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-ESB-I (S1))
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University of Pennsylvania
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Mastellos, Dimitrios C; Reis, Edimara S; Yancopoulou, Despina et al. (2018) Expanding Complement Therapeutics for the Treatment of Paroxysmal Nocturnal Hemoglobinuria. Semin Hematol 55:167-175
Reis, Edimara S; Mastellos, Dimitrios C; Ricklin, Daniel et al. (2018) Complement in cancer: untangling an intricate relationship. Nat Rev Immunol 18:5-18
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Chen, Lan-Sun; Kourtzelis, Ioannis; Singh, Rashim Pal et al. (2018) Endothelial Cell-Specific Overexpression of Del-1 Drives Expansion of Haematopoietic Progenitor Cells in the Bone Marrow. Thromb Haemost :
Lamont, Richard J; Koo, Hyun; Hajishengallis, George (2018) The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol 16:745-759
Bostanci, Nagihan; Bao, Kai; Li, Xiaofei et al. (2018) Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate Periodontitis. J Proteome Res 17:3153-3175
Ricklin, Daniel; Mastellos, Dimitrios C; Reis, Edimara S et al. (2018) The renaissance of complement therapeutics. Nat Rev Nephrol 14:26-47

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