Over the past several years, zebrafish have proven to be a valuable model to study motor neuron degeneration and search for new treatments. To date, several key mutations that cause ALS in humans (SOD1, TDP-43, FUS, etc.) have been introduced to zebrafish resulting in motor neuron dysfunction and and paralysis. These models not only provide an opportunity to study disease mechanisms with a goal of better understanding ALS, but they are also important tools for screening potential therapeutics to see if motor dysfunction can be slowed down using systems designed to robotically test thousands of substances in a single experiment. A substance is applied to the water they swim in and they are examined to see if impairment is slowed. In 2011, the most common ALS mutation was discovered as an abnormally long piece of DNA in a gene called C9ORF72. To date, some difficulty has arisen in the creation of C9ORF72 zebrafish models that resemble the actual genetic abnormality in humans. Through this Discovery Grant, Dr. Gary Armstrong will use an advanced gene editing technique called CRISPR/Cas9, including a novel modification he invented, to more accurately accomplish this goal. If successful, Dr. Armstrong’s zebrafish could represent a very valuable resource for the ALS research community and provide an important new tool for therapeutic screening.