The proposed Jacob Javits Center will be devoted to studies of the slow infectious agents or prions causing scrapie and Creutzfeldt-Jakob disease (CJD). Seven established, senior investigators will comprise the nucleus of this research effort. All the investigators have already participated in collaborative studies on prions and are continuing to do so. Recent, methodologic advances, including the production of antibodies to the scrapie prion protein and the cloning of the cDNA encoding this protein, provide a firm foundation for any new approaches to the study of degenerative neurologic diseases. Our investigations will focus on the structure of the prion, its mode of replication and the mechanisms by which it causes CNS degeneration. Additional studies are directed toward understanding the formation of prion amyloid plaques, the chemical pathology of scrapie and CJD, the structural differences between scrapie and CJD prions, identification of genes controlling the resistance and susceptibility of mice to scrapie, and determination of the role of prion genes in Gerstmann-Straussler syndrome and possibly Alzheimer's disease. The Javits Center provides an ideal vehicle for bringing together a group of talented scientists with expertise in a large number of highly specialized disciplines. The complexities of prion research program demand a multidisciplinary approach and require expertise in virology, immunology, molecular cloning, experimental neurology, protein chemistry, x-ray crystallography, neuropathology, cell biology, ultrastructure, physical biochemistry, murine genetics, amino acid sequencing, neuropeptide analysis, protein biosynthesis and processing, as well as protein structure analysis. All of the investigators have outstanding records of achievement in one or more of these scientific disciplines. Recent collaborations among these investigators have led to 1) molecular cloning and identification of host genes encoding the prion protein, 2) demonstration that amyloid plaques in the brains of animals infected with scrapie are composed of prion proteins, 3) identification of CJD prions isolated from human brains, and 4) compelling evidence demonstrating that prions are novel infectious pathogens and are not tyical viruses. Creation of a Javits Center will allow us to build upon these significant achievements. Learning about the novel structure and replication mechanisms of prions will undoubtedly lead to important revisions in our thinking about the pathogenesis of degenerative CNS disorders.
Showing the most recent 10 out of 90 publications
