The main role of the Administration Core is to evaluate and coordinate advances in the research among the three research projects and multiple institutions participating in the Center proposal. Project 1 will define the structural/biochemical basis for IFN-antagonist-host factor interactions and define the impact of these interactions on DC maturation and function. Project 2 will address the hypotheses that that the disrupted maturation of DCs induced by EBOV and MARV infection will lead to impaired T cell activation and aberrant/absent T cell function and that the mechanisms of the filoviral IFN-antagonist proteins make key contributions to these outcomes. Project 3 will characterize the phenotype and functional status of dendritic cells and lymphocytes during filovirus infection in vivo. These studies will be carried out at four different institutions by seven different laboratories. To ensure that the progress of this integrated research program will be maximized, the Administration Core (Core A) will be responsible for the following roles: Coordinate: weekly (at a minimum) teleconferences between the Pis of the research projects and cores; monthly (at a minimum) scheduled web-based interlab meetings to exchange and critique data; and an Annual Meeting among members of all participating groups and the Scientific Advisory Board (SAB) to assess scientific progress. These meetings will facilitate reagent and scientific exchanges between the different laboratories. It will also coordinate annual participation in the annual National IMVC Program meeting. In addition, the Administration will coordinate budget issues. It will assist the investigators with manuscript preparation and submission of annual progress reports to the NIH. It will also maintain a web site for data dissemination in connection with this project and facilitate data sharing and regulatory compliance. Core A will include an Administrator, hired specifically for this purpose and Dr. Thomas Moran, an accomplished viral immunologist with significant prior experience serving as PI of multi-investigator Center grants. Dr. Moran will provide advice to Dr. Basler who will serve as overall PI and supervisor or Core A.

Public Health Relevance

Ebola viruses are important emerging and biodefense pathogens for which approved therapeutic approaches are lacking. The proposed characterization of immune evasion mechanisms and their contribution to pathogenesis will suggest new therapeutic strategies. The Administration Core will provide necessary support to maximize the productivity and interaction of the laboratories performing this work.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI109945-06
Application #
9444346
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
2020-02-29
Budget Start
2018-03-01
Budget End
2019-02-28
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Georgia State University
Department
Type
DUNS #
837322494
City
Atlanta
State
GA
Country
United States
Zip Code
30302
Edwards, Megan R; Liu, Hejun; Shabman, Reed S et al. (2018) Conservation of Structure and Immune Antagonist Functions of Filoviral VP35 Homologs Present in Microbat Genomes. Cell Rep 24:861-872.e6
Su, Zhaoming; Wu, Chao; Shi, Liuqing et al. (2018) Electron Cryo-microscopy Structure of Ebola Virus Nucleoprotein Reveals a Mechanism for Nucleocapsid-like Assembly. Cell 172:966-978.e12
Knoverek, Catherine R; Amarasinghe, Gaya K; Bowman, Gregory R (2018) Advanced Methods for Accessing Protein Shape-Shifting Present New Therapeutic Opportunities. Trends Biochem Sci :
Johnson, Britney; VanBlargan, Laura A; Xu, Wei et al. (2018) Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability. Immunity 48:487-499.e5
Younan, Patrick; Iampietro, Mathieu; Bukreyev, Alexander (2018) Disabling of lymphocyte immune response by Ebola virus. PLoS Pathog 14:e1006932
Chanthamontri, C Ken; Jordan, David; Wang, Wenjie et al. (2018) Ebola Viral Protein 35 N-terminus is a Parallel Tetramer. Biochemistry :
Bharaj, Preeti; Atkins, Colm; Luthra, Priya et al. (2017) The Host E3-Ubiquitin Ligase TRIM6 Ubiquitinates the Ebola Virus VP35 Protein and Promotes Virus Replication. J Virol 91:
Menicucci, Andrea R; Versteeg, Krista; Woolsey, Courtney et al. (2017) Transcriptome Analysis of Circulating Immune Cell Subsets Highlight the Role of Monocytes in Zaire Ebola Virus Makona Pathogenesis. Front Immunol 8:1372
Dilley, Kari A; Voorhies, Alexander A; Luthra, Priya et al. (2017) The Ebola virus VP35 protein binds viral immunostimulatory and host RNAs identified through deep sequencing. PLoS One 12:e0178717
Postler, Thomas S; Clawson, Anna N; Amarasinghe, Gaya K et al. (2017) Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials. Syst Biol 66:463-473

Showing the most recent 10 out of 46 publications