The proposed U19 program, Modeling Affinity Maturation at the Molecular Level, is a large, multi-institution effort. Therefore, communication among the researchers is essential and must be made seamless and as effortless as possible for the participants. The administrative core will serve as a resource to the U19 team as a whole, providing management, coordination, and supervision of the program. Thomas Kepler is the director of the Model Development, Data Analysis, and Simulation for Affinity Maturation project and will also serve as the director of the Administrative Core. In this capacity, he will be responsible for managing and coordinating communications with the NIH and among U19 team members. He will also provide oversight of fiscal accountability. The PIs, Dr. Kepler and Dr. Kelsoe, will together be responsible for oversight of all research activities and planning. Dr. Kepler will take primary responsibility for mathematics and computation; Dr. Kelsoe will take primary responsibility for biology and experimental work. In addition, Dr. Kepler will take primary responsibility for financial oversight. The administrative core director and scientific program manager will monitor progress in each project against milestones and timelines and work with Professor Kelsoe to refine research strategies and resolve conflicts as necessary. The scientific program manager will establish web-based project management tools whose pages will be accessible to the project directors, schedule bi-weekly web-based meetings among the distributed researchers; maintain a repository of meeting minutes, technical reports, and threaded scientific exchanges; and organize the preparation of progress reports and presentations to program staff at NIH and the executive committee. Resource Sharing and outreach are important components of the program. All models produced under this U19 will be exported to SBML format and uploaded to BioModels.net. All data will be uploaded to IMMPort upon publication or one year after final preparation, whichever is sooner. Following the characterization and peer-reviewed publication of the transgenic mouse strain generated, mice will be freely distributed to investigators at academic institutions wanting mice for non-commercial research. We will engage graduate students and postdoctoral fellows in cross-disciplinary training, develop and host two summer schools and symposia, and contribute models, methods and data to the scientific community through specific, organized outlets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI117892-01
Application #
8894986
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2015-04-15
Budget End
2016-03-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
Finney, Joel; Yeh, Chen-Hao; Kelsoe, Garnett et al. (2018) Germinal center responses to complex antigens. Immunol Rev 284:42-50
McCarthy, Kevin R; Watanabe, Akiko; Kuraoka, Masayuki et al. (2018) Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires. Immunity 48:174-184.e9
Kelsoe, Garnett; Haynes, Barton F (2018) What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling. Cold Spring Harb Perspect Biol 10:
Finney, Joel; Kelsoe, Garnett (2018) Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design. Retrovirology 15:53
Cale, Evan M; Gorman, Jason; Radakovich, Nathan A et al. (2017) Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop. Immunity 46:777-791.e10
Takahashi, Yoshimasa; Kelsoe, Garnett (2017) Role of germinal centers for the induction of broadly-reactive memory B cells. Curr Opin Immunol 45:119-125
Wheaton, Joshua D; Yeh, Chen-Hao; Ciofani, Maria (2017) Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt ROR?t+ and Follicular Phenotypes. J Immunol 199:3931-3936
Kuraoka, Masayuki; Snowden, Pilar B; Nojima, Takuya et al. (2017) BCR and Endosomal TLR Signals Synergize to Increase AID Expression and Establish Central B Cell Tolerance. Cell Rep 18:1627-1635
Hwang, Joyce K; Wang, Chong; Du, Zhou et al. (2017) Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies. Proc Natl Acad Sci U S A 114:8614-8619
Kepler, Thomas B; Wiehe, Kevin (2017) Genetic and structural analyses of affinity maturation in the humoral response to HIV-1. Immunol Rev 275:129-144

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