Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Omar Benzakour, Université de Poitiers
- Second opponent: Professor Christian Heinis, École polytechnique fédérale de Lausanne
- Thirs member of the adjudication committee: Professor Jason Matthews, University of Oslo
Chair of the Defence
Professor Jan Oxholm Gordeladze, University of Oslo
Principal Supervisor
Professor Sandip Kanse, University of Oslo
Summary
Factor seven activating protease (FSAP) is a serum protein, and it is thought to be involved in coagulation, stroke, myocardial infarct and sepsis. Moreover, 5% of the European population carries a genetic variant of the FSAP called Marburg-I (MI-FSAP), and people with MI-FSAP might be more susceptible to liver fibrosis, carotid stenosis and stroke. FSAP cleaves other proteins as its substrates, and this results in change or termination of the substrate protein function. Even though, there are some information and ongoing studies on FSAP and MI-FSAP, substrate specificity of FSAP has not been studied yet.
The aims of this thesis were to study FSAP and MI-FSAP target recognition, to design probes to measure FSAP activity, and to construct a new phage-display library for protease substrate profiling with improved features.
Phage-display is a method for studying interactions between peptides and proteins. Phages are bacterial viruses, and they are engineered to carry different peptides fused to their coat protein.
A new advanced phage-display library was designed, containing randomized 12 amino acid long peptides placed in between 3X FLAGtag and phage minor phage coat protein pVII for protease substrate profiling. Using phage-display and complementary techniques, FSAP and MI-FSAP substrate specificity were revealed and two new fluorescent probes were designed to measure the FSAP activity.
The information about the FSAP recognition and new probes could be useful for further research on the role of FSAP in health and diseases. The new phage-display library was tested and proven that it can be used for any protease of interest.
Additional information
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