Scientists make a discovery to boost drug development St Vincent's Institute of Medical Research has uncovered how a protein, called the C1C chloride channel, works at a molecular level. MELBOURNE scientists have made a world-first discovery that could lead to new and ­improved drugs to treat ­diseases ranging from epilepsy to mental illness. The channels, which let chloride flow in and out of cells, are involved in a range of vital bodily functions. St Vincent's structural ­biology head Michael Parker said the C1C chloride channels act like switches and pumps, allowing nerves and muscles to talk to each other using electrical signals. Mutations in these channels cause a variety of human diseases, ranging from ­epilepsy, myotonia, kidney stones, renal salt loss, deafness, osteopetrosis and lysosomal storage disease. The channels are also behind the fainting goat phenomenon, because of the role they play in making muscles contract and rest. This bizarre situation ­occurs when startled animals freeze and collapse on their sides. In the fainting goat, the mutant channel does not open and close correctly. It means the goat's muscles cannot relax, so they stay contracted and the goat falls over. Dr Brett Bennetts said the mutant channel they looked at failed to open, leading to the defect seen in the muscle of fainting goats. For the first time, in a paper published in the noted Nature Communications journal, Professor Parker and Dr Bennetts show the way in which the chloride channel's switches open and close at a molecular level. Dr Bennetts said the research could lead to new and more sophisticated treatments for rare diseases ranging from osteopetrosis, Bartter syndrome, Dent's disease and myotonia congenita. That the channels open and close under certain conditions was discovered about 25 years ago, but no one was able to figure out how it works. That's the crucial part of the work that we have done; figuring out the mechanism at a molecular level that opens and closes them. By understanding how the channels work when they malfunction, it can better understood how they should operate in a normal situation. It appears that the work could also be applicable to the eight other channel family members in humans, which could help with improved drug development for mental illness and epilepsy. There are nine different members of this family in humans that do everything from bone absorption and salt reabsorption to lysosomal storage in the central nervous system and they all appear to work using the same mechanism. The next step is to use this knowledge to design drugs that target these channel's functions, which will lead to new treatments for a number of diseases and may decrease the unwanted side effects of existing treatments. Their work builds on the Nobel Prize winning work of US researcher Roderick MacKinnon who won the top award for showing for the first time what ion channels look like.