Digital Public Defence: Fatima Heinicke
MSc Fatima Heinicke at Institute of Clinical Medicine will be defending the thesis “microRNA profiles in CD19+ B cells in rheumatoid arthritis and the impact of microRNA sequencing library preparation” for the degree of PhD (Philosophiae Doctor).
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.
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
- First opponent: Scientific Researcher Simonas Juzenas, Kiel University, Germany
- Second opponent: Professor Pål Sætrom, Norwegian University of Science and Technology
- Third member and chair of the evaluation committee: Professor II Hilde Berner Hammer, University of Oslo
Chair of the Defence
Associate Professor Victor Greiff, University of Oslo
Professor Benedicte Alexandra Lie, University of Oslo
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which is not curable, but effective treatment at an early stage is essential to avoid severe joint destruction and to keep the disease under control. This is impeded by varying and unpredictable treatment response of patients. The precise pathogenesis of RA is unknown, but lymphocytes, including CD19+ B cells, have been reported to play a pivotal role. B cell development and functioning are controlled by gene-regulatory mechanisms. One of these mechanisms are microRNAs (miRNAs) that regulate gene expression at a post-transcriptional level. For studying miRNAs, their expression can be assessed using high-throughput sequencing. This requires pre-processing of the samples including library preparation. However, this process has been reported to introduce biases in the miRNA abundance.
In this thesis, we compared the performance of 8 library preparation kits. We showed that miRNA quantification is heavily influenced by the kit used. Consequently, the comparison of miRNA sequencing results generated using different kits is impeded and should be made with caution. Furthermore, our results can guide analysts in the selection of the most appropriate kit for the experimental set-up of interest.
Taking this into consideration, we assessed the global miRNA repertoire in CD19+ B cells from treatment-naïve and methotrexate (MTX) treated RA patients and healthy controls. Significant miRNA expression differences were observed between the MTX treated RA group and the two others. miRNA-target enrichment analysis revealed enriched target genes with known functions during B cell activation, differentiation and B cell receptor signaling. These results indicate important regulatory functions of miRNAs in CD19+ B cells in MTX treated RA patients. The study can serve as the basis for future investigations of miRNA-gene interactions in B cells in RA and the predictive power of miRNAs in RA treatment response.
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