The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Download Zoom here
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
See Digital Trial Lecture.
Adjudication committee
- First opponent: Associate Professor Kristine B. Arnvig, University College London, UK
- Second opponent: Professor Digby F. Warner, University of Cape Town, South Africa
- Third member and chair of the evaluation committee: Professor Dominique A. Caugant, University of Oslo
Chair of the Defence
Professor II Truls E. Bjerklund Johansen, Faculty of Medicine, University of Oslo
Principal Supervisor
Professor Tone Tønjum, Institute of Clinical Medicine, University of Oslo
Summary
Tuberculosis (TB) is an infectious disease caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb). During infection, Mtb is continuously exposed to stress from the host immune system. In order to adapt and survive, Mtb counts on its defence mechanisms, which are tightly regulated and rely on rapid adjustments of gene expression in response to external stimuli. Small RNAs (sRNAs) are important regulators of gene expression and play a central role in the adaptation of the bacterium to the different environments encountered throughout its life cycle.
The aims of this thesis were to study the response of Mtb to various forms of infection-related stress (nitrosative, oxidative, alkylative, and DNA damage) and liquid culture supplements at the transcriptomic and proteomic levels, as well as to investigate the presence or absence of sRNAs under these conditions. To this end, we employed high-throughput RNA sequencing (RNA-seq), mass spectrometry, bioinformatics analysis, molecular biology techniques, and genetic tools.
The most significant transcriptomic alteration was observed under nitrosative stress. Notably, eight genes involved in genome maintenance were commonly induced in three of the conditions tested. Mtb cells exposed to nitrosative stress were subsequently subjected to proteomic analysis, yielding certain overlaps between the transcriptomic and proteomic responses. These included the induction of the efflux pump Rv1687c and the predicted methyltransferase Rv1405c. Not unexpected, for many genes the transcript levels did not correlate directly with the levels of their protein products.
When a rich supplement was added to liquid media, increased sensitivity and shortened time for detection of mycobacteria in clinical samples was achieved by culture. RNA-seq analysis revealed that this response was related to down-regulation of dormancy genes.
In addition, the catalogue of mycobacterial sRNA candidates differentially expressed under the conditions tested was expanded.
Collectively, the findings presented contribute to a better understanding of the complex responses of Mtb to external stimuli, as well as to improving TB diagnostics.
Additional information
Contact the research support staff.
