Recorded: 01 Aug 2003
I was at Brandeis before I came to Cold Spring Harbor Lab. When I arrived here in 1991, I came with four new mutants that we had identified in a behavioral screen at Brandeis. It took about five people most of the 1990’s to identify the molecular lesion associated with those four new mutants.
In 2000, when we had sixty new mutants from our screen here, it took us roughly one year to identify the molecular lesions of all sixty mutants. What’s the difference? The difference is the availability of the drosophila genome sequence. In 2000 with that sequence available it was easy to identify the molecular lesions of these mutations. In 1991 without that information, it was a much more difficult process to find those genes. So we anticipated this in 1995, 1996, and it’s why we started the mutagenesis then, and used the transposon mutators to make the mutations then. Since we know the transposon sequence, we could pull that piece of genomic DNA out of the mutant fly and there would be a piece of flanking DNA attached to it next to the site where it was inserted. Then with one sequencing run of a hundred base pairs, we would know the DNA sequence of that flanking piece of DNA. If the entire sequence of the fly is available, then you can immediately match that to a unique spot in the fly genome and you know where your mutation is.
So we knew that the fly genome sequence was going to be available around the year 2000, and we knew it would take about four years to generate 6,700 mutant lines and screen them behaviorally and do the behavioral characterizations that would tell us that we have a new memory mutant. With that as anticipation, that was the approach that we took knowing that it would be easier to clone these genes when we finally found the mutant, and that was true.
Tim Tully is a molecular geneticist, interested in finding the genetic and biological basis of memory in order to better identify pharmacological and behavioral treatments for memory loss. In 1981, he received his Ph.D. from the University of Illinois. Tully joined the Cold Spring Harbor Laboratory staff in 1991 to work on discovering genes involved with memory. He became the St. Giles Foundation Professor of Neuroscience and led the Drosophila learning and memory program. In 1998 he founded Helicon Therapeutics, Inc., a development-stage biotechnology firm that works on new therapies for memory loss and other cognition disorders. In June, 2007, Tully left Cold Spring Harbor Laboratory to become Helicon's Acting Chief Scientific Officer, and assume a key role in the Michigan-based Dart Foundation as it expands its interest in funding neuroscience research.
His work on the transcriptional factor CREB gave way to the first experimental demonstration of enhanced memory formation in genetically engineered animals. Tully works to identify genes involved with long-term memory formation. Tully has determined that by the regulation of gene expression, new, long-term memories can be formed due to the growth of new synapses.