Medical Scientist-Programm 2023

Thema: "The Unfolded Protein Response as a protective mechanism In Sepsis—TUPRIS"

Zusammenfassung:
Sepsis describes a common elusive medical syndrome that was redefined as a combination of infection that is associated with organ dysfunction. The molecular processes leading to organ dysfunction in septic patients are still poorly understood. Animal studies from others and us indicate that expression of genes regulating cellular metabolism are essential for the maintenance of organ function. Preliminary data leading to this proposal shows that polymicrobial sepsis induces a hypometabolic response, which could have an important impact by reducing disease severity during sepsis. However, the underlying mechanism leading to hypometabolism during sepsis is still unclear. The hypothesis of TUPRIS is that the Unfolded Protein Response (UPR) is as a protective mechanism in sepsis and underlies sepsis-associated hypometabolism. For this, I will perform complementary gain- and loss-of function approaches in mice of different genotypes subjected to a polymicrobial sepsis and subsequential secondary infection. I expect that by blocking activation of the UPR, mice will fail to induce hypometabolism during sepsis increasing disease severity. The results from this project will reveal how metabolic adaptation is achieved during severe systemic infections and shall identify the UPR as an attractive therapeutic target.