Commonly referred to as blood poisoning, sepsis is a dysfunction whereby an inflammatory immune response is launched to combat infection. It is caused by micro-organisms such as bacteria, fungi or viruses that enter the body, overwhelming the immune system in the process. And if the immune cells are unable to contain them, germs can get into the bloodstream and spread further. What starts as a local infection becomes systemic and the immune system can go into overdrive, with potentially fatal consequences.
New process unlocks fresh research insights
The endothelium – a thin layer made up of endothelial cells – plays an important role in sepsis. It lines the inside (lumen) of blood vessels, serving as a barrier between the blood and tissue. Sepsis causes the endothelium to break down, which allows blood to escape, leading to a drop in blood pressure, oedema and ultimately organ failure. “We are building up new, physiologically relevant test systems as part of the flagship research, technology and innovation (RTI) project, which we hope will enable us to carry out in-depth research into the interactions between the overreacting immune cells and the endothelium. To accomplish this we are using optogenetic methods,” says project manager Prof. Christoph Wiesner.
Switching cells on and off
As the name suggests, optogenetics relies on a combination of genetic and optical methods to activate (gain of function) or deactivate (loss of function) certain events in specific cells or living tissue samples. The process was first developed in 2002 for use in neurology and was named method of the year by the Nature Methods editorial board in 2010. As the editorial put it at the time (DOI: 10.1038/nmeth.f.321), optogenetics changed the face of neurological research forever. In the meantime, this method has come to be used in various forms in other areas, too. To make more accurate examinations of infections possible, domains (isolated from plants or algae) that can be activated by light are fused with effector proteins. These procedures make it possible to switch inflammation pathways – which play such an important role in cases of sepsis – on or off using light. “This opens the door for targeted research into the molecular mechanisms that are triggered in the individual cells. Ideally, we will find new target molecules, or targets for short, that we can go on to use in order to improve diagnostics and treatment,” Wiesner confirms.
About the project
The aims of the Inflammation, Sepsis and Regeneration project are to improve diagnostic options through faster diagnosis of systemic infections; to generate physiologically relevant cell culture models in order to investigate the central role of the endothelium in sepsis; and to study the effect of the removal of inflammatory mediators by extracorporeal adsorption therapies in sepsis patients. The RTI project is supported by the Province of Lower Austria and conducted in partnership with Danube University Krems, which is leading the project, as well as St. Pölten University Hospital.
About Christoph Wiesner
Prof. Christoph Wiesner is a project manager at the Department of Life Sciences at IMC University of Applied Sciences Krems. He has many years of experience in project management and in setting up complex tissue and disease models, including full skin equivalents, miniaturised tumour spheroids, intestinal and sepsis models, and optogenetic cell models. His group’s core competences are establishing 3D models for the study of active ingredients (high-content screening), and explaining the cellular and molecular mechanisms in disease progressions, as well as for the identification of therapeutic targets.