Systematic profiling of molecular changes during prion disease progression

Projektinformationen

Prionomics

ID Finanzhilfevereinbarung: 706138

DOI 10.3030/706138

Abgeschlossenes Projekt

EK-Unterschriftsdatum 24 Februar 2016

Startdatum 1 März 2016

Enddatum 28 Februar 2018

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten € 175 419,60

EU-Beitrag € 175 419,60

Koordiniert durch

UNIVERSITAT ZURICH
Switzerland

Ziel

Prion diseases are fatal neurodegenerative diseases and are caused by proteinaceous infectious particles termed prions. The infectious agent of prion diseases has been identified decades ago, but the actual cellular processes that subsequently cause neurons to degenerate remain poorly understood.
I propose the systematic analysis of molecular changes in various organs from prion-infected mice. I will profile translation rates and mRNA abundance on a genome-wide scale via ribosome profiling and RNA sequencing, respectively. This will allow me to identify molecular changes during prion disease progression and to decipher the relative contributions of differential transcriptional and translational regulation to them. By relating these changes to prion titers and clinical symptoms I will establish correlations between molecular changes and disease progression. This will identify single genes as well as gene networks that are linked to disease pathology. The analysis of various organs at multiple time points following prion inoculation will enable me to dissect the dynamics of disease progression and the role and interplay of the different organs in pathophysiology.
I will further study the causal role of identified candidate genes in prion pathology. To this end, I will investigate the effect of their knock-down and knock-out on prion clearance, replication and toxicity, using a previously established fully automated digital prion infectivity assay. This approach will identify a comprehensive list of genes that are differentially regulated during prion disease progression and that are important for different aspects of prion pathogenesis. This will not only help to better understand the manifestation of prion disease and other neurodegenerative diseases but also provide potential starting points for the development of targeted therapeutic interventions.

Wissenschaftliches Gebiet

• medical and health sciences › basic medicine › neurology › dementia › alzheimer
• medical and health sciences › basic medicine › physiology › pathophysiology
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › protein folding
• medical and health sciences › basic medicine › pathology
• medical and health sciences › basic medicine › neurology › parkinson

Programm/Programme

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Thema/Themen

• MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)

Aufforderung zur Vorschlagseinreichung

H2020-MSCA-IF-2015

Finanzierungsplan

MSCA-IF-EF-ST - Standard EF

Koordinator

UNIVERSITAT ZURICH

• Netto-EU-Beitrag: € 175 419,60
• Adresse: RAMISTRASSE 71 ; 8006 Zurich ; Schweiz
• Region: Schweiz/Suisse/Svizzera › Zürich › Zürich
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 175 419,60