This project will focus on unique roles of FUS (an ALS gene/protein) at the junction where neurons connect, called the synapse. Most of the work done on FUS focuses on its functions in the central region of the neuron called the cell body. When there is a mutation in the FUS gene, it causes ALS and it is important to consider all ways in which this altered FUS can cause motor neuron degeneration. By focusing on the synapse, Dr. Sephton will carve a niche in the field of ALS research that not only should reveal important information on its effects when the disease is occurring, but will also complement the work being done by others in the cell body. Undoubtedly, the discoveries that are made over the next three years in the Sephton lab will either reveal information that will lead to a better understanding of how ALS occurs or hopefully provide new targets for therapy in an effort to make ALS a treatable, not terminal disease.