Abstract

We propose to use systems approaches to attempt to delineate some of the components in the prion and dopple informational pathways. This includes cloning and characterizing modifier genes for prion and dopple activity (e.g., neurodegenerative diseases) and rigorous similarity searches of the emerging human and mouse sequence to identify other prion-like genes. We also propose to perturb the prion system, both in vivo and in vitro, genetically (knockouts, overexpression) and/or biologically (infection) to determine the quantitative interrelationships of the relevant gene products. We will use DNA array technologies and later proteomics technologies. In this manner we hope to gain insights into the prion informational pathways.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS041997-02
Application #
6642392
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
2002-08-01
Project End
2003-07-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
Mc Laughlin Research Institute
Department
Type
DUNS #
City
Great Falls
State
MT
Country
United States
Zip Code
59405

  Publications

Chaverra, Marta; George, Lynn; Mergy, Marc et al. (2017) The familial dysautonomia disease gene IKBKAP is required in the developing and adult mouse central nervous system. Dis Model Mech 10:605-618
Daude, Nathalie; Lee, Inyoul; Kim, Taek-Kyun et al. (2016) A Common Phenotype Polymorphism in Mammalian Brains Defined by Concomitant Production of Prolactin and Growth Hormone. PLoS One 11:e0149410
Anderson, Sarah R; Lee, Inyoul; Ebeling, Christine et al. (2015) Disrupted SOX10 function causes spongiform neurodegeneration in gray tremor mice. Mamm Genome 26:80-93
Wegmann, Susanne; Maury, Eduardo A; Kirk, Molly J et al. (2015) Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity. EMBO J 34:3028-41
Park, Laibaik; Koizumi, Kenzo; El Jamal, Sleiman et al. (2014) Age-dependent neurovascular dysfunction and damage in a mouse model of cerebral amyloid angiopathy. Stroke 45:1815-21
Lausted, Christopher; Lee, Inyoul; Zhou, Yong et al. (2014) Systems approach to neurodegenerative disease biomarker discovery. Annu Rev Pharmacol Toxicol 54:457-81
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
Gunn, Teresa M; Carlson, George A (2013) RML prions act through Mahogunin and Attractin-independent pathways. Prion 7:267-71
Flores, Mauricio; Glusman, Gustavo; Brogaard, Kristin et al. (2013) P4 medicine: how systems medicine will transform the healthcare sector and society. Per Med 10:565-576
George, Lynn; Chaverra, Marta; Wolfe, Lindsey et al. (2013) Familial dysautonomia model reveals Ikbkap deletion causes apoptosis of Pax3+ progenitors and peripheral neurons. Proc Natl Acad Sci U S A 110:18698-703

Showing the most recent 10 out of 29 publications