Molecular Mechanisms of Membrane Sorting and Biogenesis in health and disease

Our goal is to identify and characterize new molecular players and pathways operating in sorting and transport events under pathological and normal conditions. In recent years, it has become clear that several genetic disorders are caused by mutations that disrupt the ability of gene products to reach the specific targets, where they would be expected to execute their functions. Among these genes, ATP7A and ATP7B encode their corresponding proteins, also known as copper (Cu) ATPases, proteins with an important role in regulating copper levels in the body. Mutations do not allow aberrant Cu ATPases to move properly through the secretory pathway to the specific sites in which Cu transport is needed, resulting in either ATP7A-dependent Cu deficiency (Menkes disease) or ATP7B-dependent Cu toxicosis (Wilson disease), which are fatal if the appropriate treatment is not executed in time. The aim of our studies is to identify regulatory mechanisms that are involved in Cu ATPase localization and trafficking and to understand their importance for the maintenance of Cu homeostasis and for the development of Menkes and Wilson disease. Therefore, we intend not only to provide answers for the above questions, but also to detect molecules that can be used for the correction of Cu ATPase transport, and therefore, for the development of novel strategies to cure Menkes and Wilson diseases. The "Total Award" amount indicated for this project represents the share of the funding of the Telethon Foundation for research by the Tigem institute from July 2016 until last budget year, calculated based on the size of the research group.