The normal function of exocrine pancreas is to secrete bicarbonate-rich fluid necessary for digestion. Our hypothesis is that this leads to acidification of extracellular pH, and together with ATP/purinergic signalling, favour micro-inflammation, epithelial transportome reorganization and PDAC development. Our aim is to resolve the dynamics and spacial resolution of pH changes and find the key proteins that are involved in intra- and intercellular signaling leading to tissue remodelling. Key candidates explored and pharmacologically tested include proton pumps, potassium channels and ATP sensitive purinergic receptors. Techniques employed will include live-cell/organ imaging, cell- and biochemical assays, multicellular organoids and orthotopic cancer models in mice.