KFO 249:  Defects of the Innate Immune System in Autoinflammation and Autoimmunity

• Subject Area: Medicine
• Term: from 2010 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 160548243

The innate immune system plays a central role in defending microorganisms and in dealing with inflammatory processes. The Clinical Research Unit focusses on identifying new pathophysiological mechanisms of hereditary diseases caused by defects in the innate immune system. The phenotypic spectrum of the disorders analysed includes periodic fever, cutane and systemic variants of lupus erythematosus as well as the Aicardi-Goutières syndrome, an autoimmunity-related encephalopathy.
A common characteristic of these diseases is the fact that their underlying genetic changes point to so far unknown mechanisms in relation to the innate immune system. On the basis of genetically determined autoinflammatory and autoimmunological disorders, the effects of mutations in genes of the innate immune system will be analysed by eight subgroups of the Clinical Research Unit at the molecular and cellular level as well as in animal models and in patients. Furthermore, the scientists will correlate effects of genetic mutations with clinical data.
The expected results are supposed to provide fundamental insights into the molecular pathogenesis of defects occurring in the innate immune system. In addition, the findings shall support the development of clinical therapies. In this regard, the gene products, their interaction partners and the signalling pathways involved do not only represent the basis for improved diagnostic possibilities. Moreover, they are potential target molecules, which can essentially contribute to the development of new causally oriented therapy approaches.

• DFG Programme: Clinical Research Units

Projects

• Aicardi-Goutières Syndrom assoziierte Genprodukte als potentielle Sensoren bzw. antivirale Effektoren gegen exogene Viren (Applicant Lindemann, Dirk )
• Analyse des Pathomechanismus beim Aicardi-Goutières Syndrom im Tiermodell: Autoimmunität durch unkontrollierte Aktivität endogener Retroelemente? (Applicant Roers, Axel )
• Beeinflussung der subzellulären Lokalisation von Pro-Caspase-1, RIP2, ASC und möglichen anderen CARD-Interaktionspartnern durch Mutationen im CASP1-Gen (Applicant Hofmann, Sigrun R. )
• Caspase-1-assoziierte Defekte der DAMP-Erkennung - Charakterisierung der Effekte von CASP1-Mutationen in humanen Zellen und einem konditionalen Casp1-knock-in-Mausmodell (Applicants Rösen-Wolff, Angela ;  Winkler, Stefan )
• Hereditäre Defekte des intrazellulären Nukleinsäure-Metabolismus als Ursache systemischer Autoimmunität (Applicants Lee-Kirsch, Min Ae ;  Tüngler, Victoria )
• Quantitative Charakterisierung von Protein-Sekretionsmustern in Caspase-1-assoziierten Sekretomen (Applicant Shevchenko, Andrej )
• Rolle von Defekten im Nukleinsäure-Metabolismus bei der Pathogenese kutaner Autoimmunerkrankungen (Applicant Günther, Claudia )
• Technologieplattform für Fluoreszenz-Korrelations-Spektroskopie (Applicant Guck, Jochen )
• Zentrale Verwaltung, strukturierte wissenschaftliche Weiterbildung, MD/PhD Programm, Biobanking, Bioinformatik, Zentrum für Seltene Erkrankungen (Applicant Lee-Kirsch, Min Ae )
• Zentrale Verwaltung, strukturierte wissenschaftliche Weiterbildung und Mediziner-Promotionskolleg (Applicant Gahr, Manfred )

• Leader: Professorin Dr. Min Ae Lee-Kirsch
• Spokesperson: Professorin Dr. Angela Rösen-Wolff