The PhD defence will be partially digital, in Kristen Nygaards sal (5370), Ole-Johan Dahls hus and streamed directly using Zoom. The host of the session will moderate the technicalities while the chair of the defence will moderate the disputation.
Ex auditorio questions: the chair of the defence will invite the attending audience at Kristen Nygaards sal to ask ex auditorio questions.
Trial lecture
"Methods for determining binding preferences of RNA binding proteins"
Time and place: February 28, 2024 11:15 AM, Kristen Nygaards sal (5370), Ole-Johan Dahls hus/ Zoom
Main research findings
Transcriptional regulation is a process by which cells produce the necessary elements to respond to a given condition. A core element of this process is the interplay between cis-regulatory regions (CRRs) and transcription factors (TFs). This thesis works on expanding the current knowledge of TF binding preferences, producing the largest compendium of high-confidence direct transcription factor binding site (TFBS) predictions, and exploring the impact of genetic variation in CRRs and its role in cancer. The JASPAR database contains high-quality, manually curated TF binding profiles across taxonomic groups. By manually curating ~30,000 TF binding profiles, we expanded this repository with ~740 new models. While computational TFBS prediction suffers from many false positives, experimental methods like ChIP-seq have been shown to include indirect TF-DNA binding events. We combined TF computational models in JASPAR with ~10,000 ChIP-seq datasets to produce high-confidence direct TFBS predictions and stored them in the last UniBind release. DNA mutations in CRRs have the potential to disrupt TF-DNA interactions and lead to transcriptional dysregulation. We explored the cancer-specific enrichment of high-impact somatic mutations and single nucleotide polymorphisms (SNPs) in gene CRRs. We found an enrichment of high-impact SNPs in 21 breast cancer-related genes.
Adjudication committee:
- Dr. Carl Herrmann, Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant)
- Dr. Anaïs Bardet, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), France
- Dr. Eivind Valen, Department of Biosciences, University of Oslo, Norway
Supervisors:
- Dr. Anthony Mathelier, Centre for Molecular Medicine,UiO
- Professor Eivind Hovig, Department of Informatics, UiO
Chair of defence:
Contact information at Department: Pernille Adine Nordby