Proteomics analysis for the identification of candidate protective proteins against sepsis

Sepsis is a life threatening condition which is associated with a systemic inflammatory reaction to a microbial infection. It can progress to severe sepsis and septic shock, whichis accompanied by a significant increase in mortality. In this project we will try to identify an endogenous protective factor against Gram negative bacterial septic shock. In this form, it is known that lipopolysaccharides (LPS), which are located in the outer membrane of Gramnegative bacteria, play an important role. The discovery that a mouse is protected from a lethal dose of LPS when it is pre-treated with a sub-lethal dose of LPS is the basis of this project. This process is called LPS tolerance. When the plasma of these protected mice is injected into a control mouse, this mouse is also protected against a lethal dose of LPS. Given that the protection against septic shock can be passively transferred via the plasma, the protective factor is therefore present herein. We will try to identify this factor by means of a separation of the plasma via different fractionation techniques, and subsequently apply proteomics experiments on the active fractions. This factor(s) will then be validated and expressed recombinant in various expression systems. This research will be the fundament for a new and effective therapy to increase the chances of survival of patients with septic shock drastically.