Many organs have of a complex structure with lumina and ducts, for example, the pancreas, liver, intestine, etc. Such organs rely on the transport of nutrients and other chemicals from the lumens to the tissue or vice versa for their function and development. These lumens and ducts are lined with epithelial cells, a polarized cell type that faces the lumen on one side (apical side) and the tissue on the other (basolateral side). The transport of nutrients is carried out by transport proteins embedded in both the basolateral membrane and the apical membrane.
The interplay of individual transport proteins in transport processes cells is what ultimately leads to the net transport events, but a solid molecular understanding of these biochemical processes is lacking. Solute transport across epithelia is a molecular process, but leading edge studies until now mainly revolve around bulk measurements, where all transporters are considered but not their unique interplay. This implies that mathematical models based on such measurements have limited predictive value when it comes to the single transport proteins. Changes in single proteins can however easily lead to disruptions in function and to diseases.
QuantiCl aims to bridge this knowledge gap by studying transcellular transport using quantitative biochemistry in epithelial cells and organoids, with specifically Chloride as the target. Chloride is an important anion in the function of many organds, for example, it is exchanged for bicabonate throughout the pancreatic duct, which is then used to neutralize stomach acid, but it is also believed to play a role in lumen formation.
Using a combination of fluorescent chloride sensors in organoids, microscopy and an image and analysis pipeline QuantiCl aims to provide quantitative insights into transcellular chloride transport, within the full complexity of the native cellular environment. These insights will provide key fundamental knowledge on how (membrane) proteins work together and take part in forming complex biological systems.
