The Science Core exists to provide reagents and services to the various projects within this Program Project grant, and to the Neuropathology and Animal Cores. The need for specific reagents and services are often common to multiple projets and cores, as they are for projects on other Program Project grants. The most efficient method of operation for providing reagents and service requiring complex, expensive equipment is therefore via a central core with highly skilled staff. For this renewal of the Program Project, the Science Core will purify prion protein (PrP) from infected rodent brains for structural studies in Project 2 , in addition to use as standards in Projects 1 and 3. It will also provide a variety recombinant Fabs and monoclonal anti- PrP antibodies, in addition to developing new anti-PrP antibodies with higher affinities. These reagents will be required in large quantities for Western blotting in projects 1, 2 and 3, immunohistochemistry by the Neuropthology core (Core C), and as specific binding controls in Project 4. Recombinant PrP will required for the screening assays in Project 3, in addition to its use as standrds in all other Projects. In addition, the Science Core will provide screening of transgenic mice from the Animal Core (Core D), particularly in support of Project for the production of novel mouse models to test the drugs developed in Projects 2 and 3. Lastly, quinacrine biodistribution studies for both human tissues from Project! and mouse tissue from Core D (in support of project 2), will be performed by the Science Core.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG002132-33
Application #
8429419
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2)
Project Start
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
33
Fiscal Year
2013
Total Cost
$210,539
Indirect Cost
$69,268
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Wan, William; Stubbs, Gerald (2014) Heterogeneous seeding of HET-s(218-289) and the mutability of prion structures. Prion 8:
Silber, B Michael; Gever, Joel R; Rao, Satish et al. (2014) Novel compounds lowering the cellular isoform of the human prion protein in cultured human cells. Bioorg Med Chem 22:1960-72
Stöhr, Jan; Condello, Carlo; Watts, Joel C et al. (2014) Distinct synthetic A? prion strains producing different amyloid deposits in bigenic mice. Proc Natl Acad Sci U S A 111:10329-34
Watts, Joel C; Giles, Kurt; Patel, Smita et al. (2014) Evidence that bank vole PrP is a universal acceptor for prions. PLoS Pathog 10:e1003990
Watts, Joel C; Prusiner, Stanley B (2014) Mouse models for studying the formation and propagation of prions. J Biol Chem 289:19841-9
Watts, Joel C; Condello, Carlo; Stöhr, Jan et al. (2014) Serial propagation of distinct strains of A? prions from Alzheimer's disease patients. Proc Natl Acad Sci U S A 111:10323-8
Wan, William; Stubbs, Gerald (2014) Fiber diffraction of the prion-forming domain HET-s(218-289) shows dehydration-induced deformation of a complex amyloid structure. Biochemistry 53:2366-70
Wan, William; Stubbs, Gerald (2014) Fungal prion HET-s as a model for structural complexity and self-propagation in prions. Proc Natl Acad Sci U S A 111:5201-6
Kurouski, Dmitry; Lu, Xuefang; Popova, Ludmila et al. (2014) Is supramolecular filament chirality the underlying cause of major morphology differences in amyloid fibrils? J Am Chem Soc 136:2302-12
Li, Zhe; Gever, Joel; Rao, Satish et al. (2013) Discovery and Preliminary SAR of Arylpiperazines as Novel, Brainpenetrant Antiprion Compounds. ACS Med Chem Lett 4:397-401

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