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PROTEODYNAMICS

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Global Dynamics of Proteolytic Quality Control Networks in Stress Response and A...

Global Dynamics of Proteolytic Quality Control Networks in Stress Response and Aging Accumulation of damaged and aggregated proteins is associated with age-related neurodegeneration in Alzheimer’s and Parkinson’s patients. The ubiquitin/proteasome system (UPS) is a major proteolytic route functioning in a cellular... ver más

31/05/2020

UNIVERSITAT ZU KOL...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITAT ZU KOLN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2020-05-31 No tenemos la información de la convocatoria

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1 Participantes

UNIVERSITAT ZU KOLN

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Líder del proyecto

UNIVERSITAT ZU KOLN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Accumulation of damaged and aggregated proteins is associated with age-related neurodegeneration in Alzheimer’s and Parkinson’s patients. The ubiquitin/proteasome system (UPS) is a major proteolytic route functioning in a cellular network that maintains the proteome during stress and aging. Degradation of damaged proteins is mediated by the 26S proteasome upon attachment of ubiquitin (Ub) proteins (ubiquitylation). Another proteolytic system supporting protein homeostasis (proteostasis) is the autophagy-lysosome pathway that degrades proteins inside activated autophagosomes. An age-related impairment of either of these systems causes enhanced protein aggregation and affects lifespan, suggesting functional overlap and cooperation between UPS and autophagy in stress and aging. Despite the progress made in searching for key substrates that are destined for degradation, the major challenge in the field is to understand how these proteolytic systems are mechanistically coordinated to overcome age-related proteotoxicity. The ultimate goal of the proposed research is to assemble a global picture of stress-induced proteolytic networks critical for aging of multicellular organisms. The tissue-specific regulation of protein degradation pathways will be addressed using the powerful genetic model of Caenorhabditis elegans. The suggested project will systematically analyze: inducible protein degradation pathways (Aim 1), the regulation of UPS and autophagy by microRNAs (miRNAs) (Aim 2), and tissue-specific adaptation of proteolytic networks (Aim 3) in stress response and aging. To this end, comprehensive transcriptome analysis, large-scale genetic screenings combined with deep-sequencing technology, and candidate approaches based on in vivo imaging and degradation assays will be performed. Together, we propose a highly complementary research plan that aims to break new grounds in the understanding of proteolytic networks in aging and disease.

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