Exploring the Insides of the Insides of Our Insides

Currently, the largest number of FDA approved drugs work by manipulating the activity of ion channels  at the plasma membrane. But the plasma membrane comprises 2–3% of the total cellular membrane, the  remaining 98% is present in organelles, and the latter harbor hundreds of transmembrane proteins that  can potentially transport ions. Organelles perform specific biochemistries within their lumens. This  biochemistry is enabled by a specialized ionic microenvironment that is likely sculpted by organelle 

resident channels and transporters. However, the precise ion levels were unknown until we developed a  technology to measure organellar ions in live cells. We recently discovered that many organelles harbor  membrane potential, indicating that vigorous ion transport occurs across organelle membranes. This  means that many transmembrane organellar proteins that are risk genes for cardiovascular,  neurodegenerative and immune diseases, that could potentially transport ions are yet to be identified as  such and characterized. Their discovery and study in native organelles was intractable until we developed  our technology to measure ions in organelles. By creating the means to study organellar ion transporting  proteins in situ, a vast and unexplored landscape for biology and medicine is now accessible.