Our long-term goal is to develop vaccines and antiviral treatments for Ebolavirus infections. We have developed biologically contained Ebolaviruses that protect mice against challenge with a lethal dose of mouse-adapted Ebolavirus.
In Aim 1, we plan to test the protective efficacy of these Ebolaviruses in guinea pigs and nonhuman primates. Towards drug development, we have established three different highthroughput screening systems that allow screening in BSL-2 containment.
In Aim 2, we propose to conduct high-throughput screening and to optimize lead compounds. The lack of effective preventive or therapeutic treatments for Ebolavirus infections is partly due to the lack of knowledge of cellular genes involved in Ebolavirus replication. Our pilot study demonstrated the potential of siRNA screening approaches to identify such genes;therefore, we plan to conduct siRNA screening of commercially available human siRNA libraries to identify critical genes for the Ebolavirus life cycle (Aim 3). Candidate genes/gene products will then be characterized to elucidate the mechanism(s) by which they interfere with Ebolavirus replication. Studies in Aim 3 may thus suggest novel approaches to the treatment of Ebolavirus infections.

Public Health Relevance

The long-term goal of this research is to develop vaccines and antiviral treatments for Ebolavirus infections. Currently, neither preventative nor therapeutic treatments are available for Ebolavirus infections, making their development an urgent task.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54AI057153-10
Application #
8448668
Study Section
Special Emphasis Panel (ZAI1-DDS-M)
Project Start
2013-03-01
Project End
2014-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
10
Fiscal Year
2013
Total Cost
$224,792
Indirect Cost
$73,093
Name
University of Chicago
Department
Type
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Schuld, Nathan J; Vervacke, Jeffrey S; Lorimer, Ellen L et al. (2014) The chaperone protein SmgGDS interacts with small GTPases entering the prenylation pathway by recognizing the last amino acid in the CAAX motif. J Biol Chem 289:6862-76
Sharma, Preeti; Wang, Ningyan; Kranz, David M (2014) Soluble T cell receptor V? domains engineered for high-affinity binding to staphylococcal or streptococcal superantigens. Toxins (Basel) 6:556-74
Pensinger, Daniel A; Aliota, Matthew T; Schaenzer, Adam J et al. (2014) Selective pharmacologic inhibition of a PASTA kinase increases Listeria monocytogenes susceptibility to ?-lactam antibiotics. Antimicrob Agents Chemother 58:4486-94
Becker, Russell E N; Berube, Bryan J; Sampedro, Georgia R et al. (2014) Tissue-specific patterning of host innate immune responses by Staphylococcus aureus ?-toxin. J Innate Immun 6:619-31
Schiano, Chelsea A; Koo, Jovanka T; Schipma, Matthew J et al. (2014) Genome-wide analysis of small RNAs expressed by Yersinia pestis identifies a regulator of the Yop-Ysc type III secretion system. J Bacteriol 196:1659-70
Stach, Christopher S; Herrera, Alfa; Schlievert, Patrick M (2014) Staphylococcal superantigens interact with multiple host receptors to cause serious diseases. Immunol Res 59:177-81
Lifshitz, Ziv; Burstein, David; Schwartz, Kierstyn et al. (2014) Identification of novel Coxiella burnetii Icm/Dot effectors and genetic analysis of their involvement in modulating a mitogen-activated protein kinase pathway. Infect Immun 82:3740-52
Merriman, Joseph A; Nemeth, Kimberly A; Schlievert, Patrick M (2014) Novel antimicrobial peptides that inhibit gram positive bacterial exotoxin synthesis. PLoS One 9:e95661
Schneewind, Olaf; Missiakas, Dominique (2014) Genetic manipulation of Staphylococcus aureus. Curr Protoc Microbiol 32:Unit 9C.3.
Wang, Ya-Ting; Missiakas, Dominique; Schneewind, Olaf (2014) GneZ, a UDP-GlcNAc 2-epimerase, is required for S-layer assembly and vegetative growth of Bacillus anthracis. J Bacteriol 196:2969-78

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