Abstract

Systems Analysis of CNS Stem Cells as Early-Stage Progression of Prion modefWe are proposing to employ systems analysis to understand the biological networks containing the prion andprion-associated molecules using CNS stem cells developed by Dr. Carlson (Projectl). CNS neurospherelines provide an excellent model system for dynamically following the course of the global changes in levelsof mRNAs and proteins as well as changes in key protein/protein and protein/DNA interactions during thecourse of prion infection in several different inbred mouse strains. Global assays will be used tocharacterize the transcriptomes, proteomes, and the interactomes in normal and disease perturbed CNSstems cell. This will enable us to construct so-called subtracted perturbation networks. These prion-perturbed networkswill delineate the dynamics of the prion-infection process and will identify key moleculesthat play a role in the biological networks mediating prion disease. They will also help provide deep insightsinto the pathophysiology of prion infection. Moreover, these studies will provide a new frame work to identifyearly diagnostic biomarkers for prion infections.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
2P01NS041997-06A1
Application #
7299476
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2007-09-15
Budget End
2008-06-30
Support Year
6
Fiscal Year
2007
Total Cost
$336,113
Indirect Cost

  Institution

Name
Mc Laughlin Research Institute
Department
Type
DUNS #
619471691
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
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
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
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

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