Epigenetic control of memory neurons in Drosophila models for COMPASS related neurodevelopmental disorders.

Intellectual disability (ID) is a major health care challenge, effecting 2-3% of the population. Thanks to recent developments in DNA sequencing technology, we now have a vast knowledge of the genetic causes of ID. Many "ID genes" code for proteins involved in epigenetics. Epigenetics regulators control gene activation by manipulating the physical structure of the genome, called chromatin, a complex of DNA wrapped around histone proteins. My lab is investigating why epigenetics is so important in the brain and what goes wrong when chromatin regulators are disrupted. In this project we will study a specific group of epigenetic regulators involved in histone methylation, a common epigenetic modification that occurs on chromatin. As a model system, we study fruit fly memory neurons that form a well characterized brain structure called the mushroom body (MB). The MB shares evolutionary origins with the mammalian cortex, which controls cognition. The development and circuitry of the MB is very well characterized, and there are many genetic tools available for manipulation of gene expression in the MB. We will use these tools to understand how disrupting H3K4 regulators impacts the molecular biology of memory neurons, and how that translates into cognitive deficits. We have already shown that H3K4 regulators are required in the MB for normal memory. In this project we will figure out why. If we can understand what goes wrong in memory neurons when H3K4 regulators are disrupted, we can start to identify and test different ways to correct that. This could lead to drug development for ID. While this project focuses on one specific group of chromatin regulators involved in ID, the tools and methods that we develop and use here can be applied to other types of genes and disorders. Therefore, our long-term goal is to widely advance the development of Drosophila models that can be used to better understand and treat neurodevelopmental disorders.