Sepsis is a life-threatening organ dysfunction resulting from severe systemic inflammation caused by an infection. Despite many improved therapeutic measures, the mortality rate from sepsis is still 15-25%, and for septic shock 30-50% (Hotchkiss et al., 2016). Endothelial cells, which line the inner surface of blood vessels and capillary beds, play a central role in this life-threatening condition. In the early stages of sepsis, microbial factors such as LPS, which binds to Toll-like receptors, are responsible for directly activating endothelial cells. Endogenous agonists – released by activated leukocytes, endothelial cells or damaged cells for instance – subsequently promote the endothelial dysfunction. In this project we plan to develop new, highly-standardised cell models in which the specific signalling pathways of the Toll-like receptors can be switched on or off by means of light induction. From the light-activatable cell lines obtained in this way, we will establish physiologically relevant models of sepsis which can then be used to investigate intracellular signalling pathways and expression of different sepsis-inducing factors, microvascular endothelial permeability, and potential therapeutic agents. The objective is to mimic sepsis-inducing inflammation by switching the signalling pathways on or off (in the absence of bacterial factors) optogenetically. The project is being carried out in cooperation with Danube University Krems and UK St. Pölten.
Development of powerful diagnostic procedures and new therapeutic approaches in inflammation and sepsis
Department of Life Sciences
- Further Information
- Status: Ongoing
- Project ID : 1201
- Project Leader
- Prof.(FH) Mag. Dr. Christoph WiesnerProfessor Department of Life Sciences