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Domestic Surveillance, Diagnosis, and Therapy of Transmissible Spongiform Encephalopathies

Objective

Objective #1 is to compare and contrast the native pathogenesis of TSEs, in order to better understand the progression and potential transmission of disease at the individual level. <P>Objective #2 is to extend existing and develop novel diagnostic tools in live and postmortem animals which can provide better epidemiological information on individual TSEs. <P>Objective #3 is to investigate both the role of environmental contamination in population-level transmission of TSEs, as well as novel means to inactivate prions in the environment. <P>Objective #4 is to develop an epidemiological model of individual TSEs which can be used to develop evidence and population -based animal management plans for TSE control. <P>Objective #5 is to investigate the nature and effect of prion strains on the pathogenesis, progression, and transmissibility of TSEs in both individual and population based approaches. <P>Objective #6 is to use pathogenomics to determine the role of genetic material in the pathogenesis of prion diseases, and identify surrogate genetic markers for the diagnosis of prion diseases.

More information

Non-Technical Summary: Until recently most research in the United States was confined to TSEs affecting individual species, with studies conducted by individual investigators focused on specifically defined problems. These individual research projects suffered from limited integration. It is the broad, long-term goal of this proposal to form a co-operative of basic and applied researchers focused on animal prion diseases that will rapidly and markedly expand the collaboration and focus of US-based TSE research. The goal of this project is to develop and maintain that activity and provide immediate support in the form of new research towards understanding, controlling, and responding to prion diseases such as BSE. This project seeks to more fully define the pathogenesis, diagnosis, and envirtonmental components of prion diseases. The study will necessariy involve both experimental molecular techniques, as well as observational epidemiological studies. <P> Approach: South Dakota State University will participate specifically in Objectives #1, 2, and 5. Dr. Tanya Graham is currently involved in diagnosis of scrapie and CWD through the South Dakota Animal Disease Research and Diagnostic Laboratory. She will collaborate with investigators to evaluate the utility of novel diagnostic techniques. Dr. Young has an active research program in the role of the immune system in prion diseases, and will specifically examine the role of B cells in prion propogation and dissemination in scrapie, CWD, and (in collaboration with other investigators) BSE. These efforts will be funded through basic research grants existing or submitted to the USDA, NIH, DOD, and others. Briefly, cell culture models will be used to define the response of ovine and cervid B cells to prion infection. Collection of iccosomes from these cultures, as well as other supernatants will allow us to develop a proteomic and genomic analysis of the secretion of factors from infected cells during disease progression. Our research has further demonstrated unique effects on B cell subsets circulating in the blood of sheep and cervids throughout prion disease. In vivo experiments will define unique changes in the composition and phenotype of peripheral blood leukocyte subsets during the progression of disease, and their potential contribution to the dissemination of the prion agent.

Investigators
Young, Alan
Institution
South Dakota State University
Start date
2005
End date
2010
Project number
SD00235-R
Accession number
205628