Cellular Pass Control: Antigen Processing and Presentation
The immune system recognizes both external invaders (bacteria and viruses) and internal aberrations (tumours). To this end, each cell has to identify itself towards the immune system by presenting intracellular peptides at the cell surface. Despite its enormous efficiency, some harmful cells escape the screening (pass control) of the immune system by presenting unsuspicious peptides only. We investigate the complex protease machinery involved in peptide processing. A detailed understanding promises treatment options against tumours and infectious diseases.
Given the increasing number of requests for high quality legumain, we teamed up with Jena Bioscience to rapidly serve the community, https://www.jenabioscience.com/proteins/recombinant-proteins/protein-kinases-phosphatases-and-peptidases/peptidases/pr-967-legumain.
Elfriede Dall received an FWF Start Grant on „Functional Studies on Extra-lysosomal Legumain”. The project page can be found here.
Undercover Agents – how pathogens escape cellular defence mechanisms
To undermine the defence mechanisms of the host, pathogens follow a classical strategy by imitating proteases of the host immune system. Of particular interest are bacterial collagenases which contribute to the host colonization and infiltration and thus enable host infection.
Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis
Eckhard U, Schönauer E, Nüss D & Brandstetter H (2011), Nat. Struct. Mol. Biol. 18: 1109–14
Structure and function of proprotein convertases
The serine protease furin has been connected to several pathologies such as rheumatoid arthritis, cancer and infectious diseases. In addition, many viruses require the proteolytic activation of their surface proteins by furin, including the measles virus, the denque virus, highly pathogenic avian influenza viruses and SARS-CoV-2. Thus, furin inhibitors are promising therapeutics against many diseases. The SARS-CoV-2 pandemic as well as the climate change related spread of tropical diseases, like denque fever, demonstrate the need for effective antiviral drugs.
Our work aims at a better understanding of the structure and fuction of proprotein convertases and structure-based development of novel furin inhibitors for the treatment of infections. Recently, a stand alone project (P36648-B) was granted to Dr. Sven O. Dahms by the Austrian Science Fund (FWF) to support this work.
Prostatic and epidermal kallikreins
Several tissue kallikreins (KLKs) are synthesised in the prostate, including KLK2, 3, 4 und 11. These serine proteases are interconnected by an activation web. Occurence of prostate cancer is accompanied by an exceeding increase of KLK3, aka PSA. Therefore, the PSA level serves as a diagnostic marker of prostate cancer, albeit prone to false positive signals. We expect to improve the diagnostic reliability by correlating the amount and the activity of all prostatic KLKs. Epidermal KLKs (KLK5, 7, 14) together with their regulator (LEKTI) play an important role in epidermal regeneration. Disturbance of the KLK regulation generates atopic dermatitis, because a first defence barrier gets disrupted.