Tuberculosis is nowadays rather uncommon disease in Finland. Nevertheless, worldwide it causes over one million fatalities each year. Thus, it is a subject of intense research. Tubercle bacillus has through the ages been able to hide the immune defense of man and to transform when it has encountered drugs. In other words, antibiotic-resistant strains are becoming more and more common and the current BCG vaccine does not prevent infection.
The challenge in tuberculosis research has been to find a research model which would mimic the versatility of tuberculosis but would also be practical and ethical. Zebrafish, which over the years has become increasingly popular as a research model, meets these challenges. A natural pathogen of zebrafish, Mycobacterium marinum, causes a chronic infection in zebrafish. This infection resembles human tuberculosis in many aspects.
In her doctoral thesis, Harjula investigates the progression of mycobacterial infection in zebrafish. The first part of the thesis concentrates on histological methods to study the changes in tissues caused by the infection. During this work, the typical structures of tuberculosis, granulomas, were detected. Also, the different phases of the infection including the spreading of bacteria into tissues were observed.
Furthermore, in the thesis, the roles of various genes in the immune defense against mycobacterial infection in zebrafish are investigated. In particular, interleukin 10, was chosen as the research subject. The role of this gene during mycobacterial infection was studied by measuring bacterial burden, gene expression and blood cell counts and with histological stainings. The results showed that the lack of interleukin 10 resulted in improved immune response to the infection. This is in consensus with the results gained in other animal models.
The final aim of the thesis work was to identify genes required for normal resistance against mycobacterial infection. To reach this aim, the susceptibility of zebrafish to mycobacterial infection was studied by performing a forward genetic screen. In addition, the expression of all genes during mycobacterial infection was studied. As a result, several genes potentially having a role in the defense against mycobacterial infection were identified. These findings give the basis for further studies. All in all, the results of this thesis further verify the status of zebrafish as a valid research model for tuberculosis.
The doctoral dissertation of Master of Science in Technology Sanna-Kaisa Harjula in the field of Applied pediatric immunology and infectious diseases titled Zebrafish as a Genetic Model to Study Tuberculosis will be publicly examined in the Faculty of Medicine and Health Technology at Tampere University starting at 12 o’clock on Friday 9 October 2020, Arvo building auditorium F114, Arvo Ylpön katu 34. The Opponent will be Professor Annemarie Meijer from the University of Leiden, the Netherlands. The Custos will be Professor Mika Rämet from the Faculty of Medicine and Health Technology.
Only a limited number of participants is allowed to the auditorium.
The event can be followed online, Zoom, meeting ID: 631 2795 9395
The dissertation is available online at
http://urn.fi/URN:ISBN:978-952-03-1589-4
Photograph: Jukka Lehtiniemi