Investigating the pathophysiological role of granzyme K in viral infections and sepsis

• Applicant: Dr. Lars Jöckel
• Subject Area: Cell Biology
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 230375312

The immune system can eliminate pathogens such as viruses and bacteria by releasing components of cytotoxic T cells. Granzymes (a group of serine proteases) together with perforin (a pore-forming delivery protein) are key factors believed to mediate cell death and therefore are indispensible for the elimination of infected cells. Recent evidence suggests that certain granzymes, such as the non-cytotoxic granzyme K possess other activities that contribute to host defence like the induction of pro-inflammatory processes. On the other hand it was shown that granzyme K is up-regulated in blood during severe inflammation and sepsis and is therefore indicative of a bad prognosis in these diseases. It is not clear how granzyme K is involved in these processes. We therefore want to analyze its role during viral infections and experimental sepsis in mice lacking granzyme K (which were recently generated at the host institution). We will identify and validate novel targets of granzyme K using spectrometric approaches and characterize in detail their contribution to inflammation, morbidity and mortality. Through research on the (patho-) physiological role of granzyme K, we can gain insights into how important granzyme K is in promoting severe outcome in viral infection and sepsis and we hope that our findings will contribute to defining new targets for treatment.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Participating Institution: Monash University ; Department of Biochemistry and Molecular Biology
• Host: Professor Dr. Phillip Bird