5. Relation and causality between pH homeostasis and driver mutation generation in PDAC development.

We hypothesize that acidic conditions synergize with PDAC mutations to drive PDAC development. An outstanding question is the causality between the two: are PDAC driver mutations more easily generated in an acidic environment, or is their ability to drive PDAC development increased due to the acidity. The experiments will be based on exposing organoid cultures that carry one, two or none of the typical PDAC driver mutations to acid conditions, and then assess changes in RNA response (RNA-seq) and generation of new mutations. This is a collaboration with project 4 "interactions between microenvironmental acidity and PDAC driver mutations studied in 3D organotypic culture" in Stine F. Pedersen's laboratory. The position is primarily computational, requiring experience in programming, statistics and bioinformatics.