Objective: Analyze the interplay between acidic conditions and central PDAC mutations in driving PDAC development.

Strategy: Organoid cultures of mouse normal pancreatic ductal cells will be exposed to (a) environmental acidic stress of varying duration and magnitude and (b) central PDAC driver mutations (KRAS, p53), alone and in combination, followed by in-depth phenotype analyses. Together with a bioinformatics ESR the ESR will analyse genotype-phenotype interactions to understand how acidity and mutations interact in PDAC.