Research
Academics & Research
VMRCVMTitle: Nanoscale Optical Fiber Biosensor Assays for Detection of Category A and B Select Agents
Significance: The threat of an intentional release of bacterial select agents prompts the need for their rapid, culture-free diagnosis that can be conducted in the field or in laboratories with only basic diagnostic capabilities. Optical fiber biosensors are attractive devices that can detect, record, and transmit information regarding a physiological change or the presence of various biological and chemical materials in the environment. These devices can be easily operated by non-specialist personnel and do not require high vacuum, high temperature, organic solvents, or clean-room facilities. Our overall goal is to develop sensitive, specific, and rapid nanoscale optical fiber biosensors for the diagnosis of the Category A and B select agents Francisella tularensis, Burkholderia mallei, and B. pseudomallei, as proof of principal that these tests can be applicable to a wide variety of other agents. Our hypothesis is that specific antigenic epitopes or regions of the DNA of these bacteria can be targeted for use in rapid, specific, and sensitive diagnostic assays. To accomplish our goal our specific aims are to: (i) develop a DNA-hybridization assay using nanoscale optical fiber biosensors coupled to DNA probes to detect specific oligonucleotide sequences; (ii) develop an antigen-binding assay using nanoscale optical fiber biosensors coupled to antibodies to detect specific antigens; and (iii) enhance the sensitivity and optimize the specificity of the nanoscale optical fiber biosensors in detecting oligonucleotide sequences and antigens specific to infectious bacteria. In addition, we will use Real-Time PCR and latex agglutination assays as control assays to compare the sensitivity and specificity of DNA-based or antigen-based optical fiber biosensor assays. The novel bioengineered optical fiber assay is rugged, portable, and inexpensive when compared to competing technologies such as surface plasmon resonance. These sensors will fill an important void that exists in the rapid diagnosis of Category A and B select agents, but can be broadly applicable and to the diagnosis of a variety of biological agents.
PI: Thomas J Inzana
CO-I: James R Heflin
CO-I: Abey Bandara
Total Award: $375,604
Direct: $250,000
Indirect: $125,604
Duration of Award: Two years
Title: Mechanisms of Immune Modulation by Probiotics
Significance: Rotavirus gastroenteritis poses a tremendous ongoing disease burden in the US and worldwide, with costs to health care and society exceeding one billion dollars annually in the US and even more immense morbidity and mortality in developing countries. Four years of funding (R01) from National Center for Complementary and Alternative Medicine (NCCAM), NIH are awarded to Dr. Lijuan Yuan and her team to determine if the use of probiotics can enhance vaccine efficacy in gnotobiotic pig models of human rotavirus infection and to identify the underlying mechanisms by which probiotics exert the adjuvant effects. Identifying a novel function of probiotics next to their role as direct regulators of disease is highly significant and innovative. This knowledge will facilitate the clinical uses of probiotic adjuvants for vaccines against rotavirus and other enteric virus-induced diseases, which could have a real impact on global health by augmenting vaccine efficacy at a relatively moderate cost.
PI: Lijuan Yuan
CO-I: Stephen Boyle, Marlice Vonck
Total Award
Direct: $1,000,000
Indirect: $1,560,523
Duration of Award: 08/01/09-07/31/2013
Title: USDA,APHIS,VS Centers for Epidemiology and Animal Health
Significance: This agreement will expand the work begun by the Veterinary Medical Informatics Lab (VMIL) in standardization of terminology for the USDA’s National Animal Health Laboratory Network, broadening the scope to include the USDA, APHIS, Veterinary Services standards for taxonomy. The work will specifically focus on updating and improving the taxonomy and breed standards published in the Surveillance and Data Standards for USDA/APHIS/Veterinary Services, used by all USDA animal programs. Improved standardization will enhance surveillance and response to emerging animal diseases in the US, including avian influenza and with bio-terrorism potential.
PI: Jeff Wilcke
CO-I: Julie Green
Total Award: $65,000
Direct: $59,101
Indirect: $5,909
Duration of Award: 09/02/08-09/01/09
Title: Identifying PRRSV structural components that activate regulatory T cells and diminish protective immunity
Significance: This research project will address an important question in Porcine Reproductive and Respiratory Syndrome virus (PRRSV) immunology by determining and characterizing which components of the virus stimulate regulatory T cells (Tregs), resulting in diminished protective immunity. A major obstacle in stimulating protective immunity against PRRSV is the ability of the virus to modulate and dampen the immune response, leading to virus persistence. This immune modulation not only allows PRRSV to replicate and cause disease, but it also leads to severe secondary respiratory infections as well. One way the virus is able to do this is by activating regulatory T cells. Regulatory T cells not only dampen the immune response to the antigen that activated them, but they also non-specifically dampen the immune response to other antigens as well. Determining which viral components are necessary for regulatory T cell activation will be vital in designing future effective vaccines that avoid this arm of the immune response.
PI: Tanya LeRoith
CO-I: XJ Meng,
Kevin Pelzer
Total Award: $59,249
Direct: $59,249
Duration of Award: 1 year, starts November 1, 2008
Funding Agency: National Pork Board
Title: Understanding the Immunopathogenesis of Porcine Multisystemic Wasting Syndrome: the Immunological Effects of PCV2 and PRRSV Co-infection
Significance: Porcine circovirus associated diseases (PCVAD), including PMWS, are widespread in the pork industry in the United States. Additionally, the incidence of more severe PMWS has been increasing. Although PCV2 has been recognized as the major contributor to PCVAD, it is difficult to reproduce the disease with PCV2 alone. Typically infection by other viruses including PRRSV is required for clinical disease. However, the contribution each virus makes to the manifestation of clinical disease is unknown, but is presumed to be a result of immune modulation by the viruses. This research will attempt to identify the contribution of each virus in enhancing disease. Understanding the effects of each virus on the immune system and how they interact is vital for vaccine development and for instituting other control measures.
PI: Tanya LeRoith
CO-I: XJ Meng,
Kevin Pelzer
Total Award: $60,669
Direct: $60,669
Duration of Award: 1 year
Funding Agency: National Pork Board
Title: Attempt transmit hepatitis E virus to goats
Significance: The objective of this study is to attempt to transmit hepatitis E virus to goats, and to establish a goat animal model for the study of human hepatitis E.
PI: XJ Meng
CO-I: D. Phillip Sponenberg
Total Award: $24,866
Direct: $15,688
Indirect: $9,178
Duration of Award: 6 months
Funding Agency: NIAID, NIH
Title: Fullerenes Counteracting Organophosphorus Threats
Significance: 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: A chicken model to study HEV pathogenesis
Significance: 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: 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