Grant: Project Grant

Proteins are string-like molecules that play many vital roles in the human body. They are made up of about 20 different building blocks called amino acids, which are in a particular sequence that enables the string to fold up into its correct 3 dimensional structure. When the sequence is changed due to a genetic mutation, the protein may not fold up correctly and cause disease. Misfolded proteins are often mislocalized and degraded, but if they can reach their normal cellular location they are still functional. This is what happens in cystic fibrosis, in which the misfolded protein is called CFTR. Drugs that correct the localization and function of CFTR have been developed, but they provide only a small benefit for most patients and better drugs are needed. We have identified new compounds that bind directly to CFTR and correct it's trafficking, but to improve them we need to answer questions such as "Where do they bind? Do different drugs bind at different sites? How do they work to trigger correction? Which combination of these correctors gives the most therapeutic benefit? These questions will be addressed in this grant proposal with a view to developing better therapies for protein trafficking diseases.