Tully is known for his research identifying genes that affect memory in the fruit fly species Drosophila melanogaster. In 1995, Tully and his CSHL colleague Jerry Yin made headlines when they genetically engineered a Drosophila fly that displayed the equivalent of a photographic memory. They did so by breeding flies with a mutated form of the CREB gene to produce many more activator proteins than it normally would, thereby allowing the flies to store more long-term memories. Through his company Helicon, Tully subsequently began working to develop a drug to raise levels of the CREB protein, in the hope that it would improve memory in humans. In 2004, Tully and his CSHL colleagues developed HT-0712, a drug that aims to improve memory in people with dementia. At the time, Tully suggested that it could also be used by healthy people to help them remember how to play a new musical instrument or speak a new language.