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 projects and cores, as they are for the projects on other Program project grants. The most efficient method of operation for providing reagents and services requiring complex, expensive equipment is therefore via a central core with a highly skilled staff. For this renewal ofthe Program project, the Science core will provide recombinant mouse PrP (with and without isotopic labels) for the generation of synthetic mammalian prions, and anti-PrP antibodies, for Project 1. Recombinant Sup35 will be produced for Project 2, in addition to constructs of Sup35 for development of transgenic mouse lines. The Science core will provide fluorescence activated cell sorting, and prepration of various A-beta aggregates (both synthetic and extracted from natural sources), for Project 3. Anti-PrP antibodies including recombinant Fabs will be supplied to the Neuropathogy core (Core C). The Animal core (Core D) will be supplied with isotopically labeled mouse diet in support of Project 1, and screening of all transgenic lines in suport of Projects 1, 2 and 3. Leadership for the Core will be provided by Dr. Kurt Giles, and Assistant Professor with over 15 years experience in neurodegenerative disease research, and by Dr Michael Silber, a Professor with over 30 years industrial and academic experience, who will act as co-director. Drs. Giles and Silber will be assisted by other scientists and research associates to provide the above functions.

Public Health Relevance

Understanding the molecular pathogenesis of prion diseases is central to ultimately developing treatments for a range of nerudegenerative disorders. The Science core supports the other projects and cores by supplying a range of reagents and services in a centralized and efficient manner.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG010770-21
Application #
8658335
Study Section
Special Emphasis Panel (ZAG1-ZIJ-6)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
21
Fiscal Year
2014
Total Cost
$260,934
Indirect Cost
$92,965
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Watts, Joel C; Giles, Kurt; Saltzberg, Daniel J et al. (2016) Guinea Pig Prion Protein Supports Rapid Propagation of Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease Prions. J Virol 90:9558-9569
Watts, Joel C; Giles, Kurt; Bourkas, Matthew E C et al. (2016) Towards authentic transgenic mouse models of heritable PrP prion diseases. Acta Neuropathol 132:593-610
Ahlenius, Henrik; Chanda, Soham; Webb, Ashley E et al. (2016) FoxO3 regulates neuronal reprogramming of cells from postnatal and aging mice. Proc Natl Acad Sci U S A 113:8514-9
Dunn, Joshua G; Weissman, Jonathan S (2016) Plastid: nucleotide-resolution analysis of next-generation sequencing and genomics data. BMC Genomics 17:958
Patzke, Christopher; Acuna, Claudio; Giam, Louise R et al. (2016) Conditional deletion of L1CAM in human neurons impairs both axonal and dendritic arborization and action potential generation. J Exp Med 213:499-515
Giles, Kurt; Berry, David B; Condello, Carlo et al. (2016) Optimization of Aryl Amides that Extend Survival in Prion-Infected Mice. J Pharmacol Exp Ther 358:537-47
Elkins, Matthew R; Wang, Tuo; Nick, Mimi et al. (2016) Structural Polymorphism of Alzheimer's β-Amyloid Fibrils as Controlled by an E22 Switch: A Solid-State NMR Study. J Am Chem Soc 138:9840-52
Lim, Kwang Hun; Dasari, Anvesh K R; Hung, Ivan et al. (2016) Solid-State NMR Studies Reveal Native-like β-Sheet Structures in Transthyretin Amyloid. Biochemistry 55:5272-8
Lim, Kwang Hun; Dasari, Anvesh K R; Hung, Ivan et al. (2016) Structural Changes Associated with Transthyretin Misfolding and Amyloid Formation Revealed by Solution and Solid-State NMR. Biochemistry 55:1941-4
Levine, Dana J; Stöhr, Jan; Falese, Lillian E et al. (2015) Mechanism of scrapie prion precipitation with phosphotungstate anions. ACS Chem Biol 10:1269-77

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