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DBSP Grant Announcements

Title: Fullerenes Counteracting Organophosphorus Threats

Signficance: Organophosphorus (OP) compounds are potent, volatile chemical agents that have been used as agents of terrorism (e.g., their use against the Kurds in Iraq in the 1980s and their release in Japan in 1994 and 1995). The OP nerve agents are chemically similar to OP insecticides and exert their acutely toxic biological effects by inhibiting acetylcholinesterase (AChE) enzyme in the nervous system. Although treatments are currently available for rescue from OP-induced cholinergic poisoning that follows AChE inhibition, they have a limited spectrum of effectiveness. Solubilized carbon-containing ‘buckyballs’ (C60 and C80 fullerenes) supplied by Luna Innovations, Inc., Blacksburg, have properties that provide potential to contribute to counteract severe OP-induced toxicity. The water solubility of these fullerenes will allow them to be easily administered and distributed in the body; properties associated with their carbon cages will allow them to enter cells to exert antidotal action. They are safe, have capability to interact with and inactivate OP compounds, and could counteract OP-induced oxidative stress associated with the severe toxicity that can occur following exposure to nerve agents. The work to be done will examine the effectiveness of C60 and C80 fullerenes to inactivate OP compounds in vitro and effectively antidote OP toxicity in vivo.

PI: Marion Ehrich
CO-I: Bernard S. Jortner; Luna Innovations, Inc. (Roger Van Tassell, Chris Kepley)

Total Award: $946,432 (includes annual subcontracts to Luna Innovations, Inc.)
    Direct: ~$674,435 total
    Indirect: ~$217,728 total

Duration of Award: ~ 3 years; 9/4/08 – 5/31/11

Funding Agency: NIH

Title: Mechanism of hepatitis E virus replication and pathogenesis

Significance: The lack of knowledge on HEV biology and pathogenesis has greatly hindered the development of a vaccine against HEV. This project will delineate the structural and functional relationship of HEV genes using reverse genetics and animal models, and the results will aid in the development of a live-attenuated vaccine against this important but extremely understudied human pathogen.

PI: X.J. Meng
CO-I: P.G. Halbur, Y.W. Huang

Total Award: $1,561,797
    Direct: $1,000,000
    Indirect: $561,797

Duration of Award: 03/01/2008 to 02/30/2012

Funding Agency: NIAID, NIH

Title: A chicken model to study HEV pathogenesis

Signficance: The lack of a practical animal model for HEV is a major obstacle for understanding the mechanism of HEV pathogenesis. This project will utilize a novel chicken model system to understand the pathogenesis of HEV, and the data from this project will help devise preventive and control strategies against HEV.

PI: X.J. Meng
CO-I: F.W. Pierson, T. LeRoith, Y.W. Huang

Total Award: $1,266,300
    Direct: $800,000
    Indirect: $466,300

Duration of Award: 03/01/2008 to 02/30/2012

Funding Agency: NIAID, NIH

Title: Protease Activation of Newcastle disease virus for Oncolytic viral therapy

Signficance: Newcastle disease virus is an avian virus that can specifically destroy human tumor cells. This project will explore genetic modification of Newcastle disease virus by reverse genetics technique in such a way that the virus will specifically infect only human tumor cells that secrete specific proteases and spare the normal cells. By this approach, it will be possible to individualize treatment for cancer patients based on the type of protease secreted.

Key Faculty Personnel:
PI: Elankumaran Subbiah
Co-PI: Siba K Samal (University of Maryland College Park campus)

Total Award:
Direct: $ 275000
Indirect: $ 159458

Duration of Award: 09/30/2007 – 08/31/2009

Title: Biofilm formation by Histophilus somni: The function of biofilm in bovine respiratory disease and colonization

Signficance: Histophilus somni is one of the gram-negative, coccobacilli responsible for Bovine Respiratory Disease Complex (BRDC). The occurrence of BRDC continues to increase, accounting for over 60% of feedlots deaths, with 62% of feedlots vaccinated for H. somni. There is a high demand for effective H. somni vaccines based on an economic analysis of the impact of H. somni diseases. Vaccines against H. somni are available, but their efficacy is questionable to nonexistent, particularly in prevention of respiratory disease or reproductive failure. We believe that the biofilm state is the normal form of existence for H. somni in the bovine host, that biofilm formation enhances H. somni colonization and pathogenesis, and that H. somni and possibly other pathogens are protected from vaccine-induced immunity and antibiotic treatment in the biofilm. This project will contribute to the knowledge about the role of bacterial biofilm in H. somni virulence and disease pathogenesis, and will eventually improve animal health through development of a successful and efficacious vaccine.

Key Faculty Personnel:
PI: Thomas J. Inzana
Co-PI: Indra Sandal
Co-PI: William K. Scarratt

Total Award:
Direct: $299,607.00
Indirect: $74,902.00

Duration of Award: 3 yrs (09/01/2007 to 08/30/2010)