Project Details
Projekt
Genetic pathogenesis of tissue injury-induced apoptosis of immunocompetent and parenchymal cells
Applicant
Professor Dr. Wolfgang Ertel, since 12/2006
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
from 2003 to 2011
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5408575
Severe tissue trauma leads to an early activation of the innate immune system with systemic inflammation followed by its downregulation and consequent immunosuppression. Both cause organ damage and finally multiple organ failure. Systemic inflammation as well as immunosuppression is characterized through a dysregulation of cell homeostasis which is predominantly regulated through apoptosis. Although some mechanisms of those tissue trauma induced immunological disorders have been described on a cellular level, the downstream gene based mechanisms of altered apoptosis need to be investigated. Using a mouse model of systemic tissue injury (hemorrhage) with or without local tissue trauma (laparotomy) it is the principal objective to explore time-dependent gene expression of apoptosis inducing proteins in correlation with functional disorders of immunocompetent and parenchymal cells. Moreover, using gene modulation with adenovirus and transfection of specific cells with vectors for anti-apoptotic proteins as well as using knock-out mice the importance of apoptosis inducing proteins will be confirmed. In addition, using microarray analyses unknown genes which may play a pivotal role for tissue damage induced apoptosis will be screened. Finally, gene expression of apoptosis regulating proteins will be determined in immunocompetent cells from trauma victims followed by gene modulation using adenovirus transfection.
DFG Programme
Priority Programmes
Ehemaliger Antragsteller
Privatdozent Dr. Andreas Oberholzer, until 12/2006
Participating Person
Dr. Sven Kevin Tschöke
