This project will focus on comprehensively studying impaired transmission of signals (from the brain) at the location where neurons and muscles meet, called the neuromuscular junction. Recent evidence from a number of labs has indicated that errors in neurotransmission of signals might be one of the first pathological effects in ALS. Using electrophysiology in zebrafish creates a novel way to study these defects and to gain an understanding in a way that might reveal new targets for therapy. In addition, Dr. Armstrong aims to revolutionize the use of zebrafish as a model for studying ALS. Using a new method called ‘clustered regularly interspaced short palindromic repeats/cas9 (CRISPR/cas9)’, which allows for efficient editing of genetic material in living organisms, he will create numerous zebrafish models that have unique alterations in ALS genes, like those encoding TDP-43 and FUS, to get a better understanding of how they cause motor neuron degeneration. Such experiments previously were not feasible on this scale in an animal model of the disease and should spark many new discoveries. In combination, these two lines of research put Dr. Armstrong in a tremendous position to take the next step in his career and to establish his own laboratory.