Research SummaryUnderstanding the mechanism of persistence of memory
The primary goal of my lab will be to understand how long term memory is maintained. Recently, DrosophilaOrb2, the homologue of translation regulator Cytoplasmic Polyadenylation Element Binding protein (CPEB), hasbeen shown to be crucial for this. It was hypothesized that due to the prion-like nature of Orb2, it regulatestranslation in a self-sustaining mechanism to perpetuate memory. Consistent with this, my work has shown thatinterfering with its prion-like activity specifically disrupts the persistence of memory without affecting its formation.
Using Orb2 as a molecular handle I plan to investigate the mechanism of memory maintenance. First, I aim to understand the regulation of Orb2. I will perform a genome wide RNAi based screen to identify candidates controlling the expression and prion-like activity of Orb2. Secondly, I aim to identify the targets of Orb2 using a tagged polyribosome pulldown method combined with next generation sequencing. I will further use behavioral assays to test the role of these candidates in maintaining memory. Finally I will investigate whether these molecules play a role in memory loss associated with neurodegenerative diseases.