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Zawartość zarchiwizowana w dniu 2024-06-18

Analysis of protein misfolding as a pathogenetic mechanism in autoinflammatory diseases

Cel

Autoinflammatory diseases (AID) are an emerging group of mainly inherited disorders that lead to an innate immune dysregulation of cytokines. The common features are recurrent episodes of inflammation with fever. Systemic amyloidosis is the primary long-term morbidity, while treatment options are scarce. Thus, AID are associated with chronic disability and a significant impact on the health care system. Current data suggest protein misfolding with loss-of-function as a missense-induced principle in three monogenetic AID: tumor necrosis factor receptor-1 associated periodic syndrome, hyperimmunoglobulinemia D with periodic fever syndrome, and familial Mediterranean fever. The objective of this project is therefore to systematically elucidate the molecular mechanisms underlying these AID with the ultimate goal to develop targeted therapeutic strategies. A high-end technological platform will be used to analyze conformation, stability and function of the three mutant proteins TNFRSF1A, mevalonate kinase and pyrin. Analyses will be supplemented by the investigation of the effect of compound heterozygosity and digenity on protein misfolding. Protein-protein interaction (PPI) partners will be analyzed by the automated bioluminescence resonance energy transfer (BRET) technology for detection of PPI in living cells, thus allowing for an in-depth functional understanding of the target proteins. A hypothesis driven approach will be established to identify candidate compounds with potential protein-stabilizing properties followed by experimental validation of the chaperone effect. This innovative, translational approach sets the ground for future targeted therapies in AID. The project also will help to reintegrate a well-recognized physician-scientist with substantial clinical and scientific expertise in AID in Germany, thereby significantly increasing European excellence, while simultaneously supporting a lasting co-operation with the United States.

Dziedzina nauki (EuroSciVoc)

Program(-y)

Temat(-y)

Zaproszenie do składania wniosków

FP7-PEOPLE-2010-RG
Zobacz inne projekty w ramach tego zaproszenia

System finansowania

MC-IRG - International Re-integration Grants (IRG)

Koordynator

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Wkład UE
€ 100 000,00
Adres
GESCHWISTER SCHOLL PLATZ 1
80539 Planegg
Niemcy
Region
Bayern Oberbayern München, Kreisfreie Stadt
Rodzaj działalności
Higher or Secondary Education Establishments
Linki
Koszt całkowity
Brak danych