Functional investigation of the SWI/SNF chromatin remodeling complex in neuronal development and function.

Recent technical innovations in the field of genomics have lead to rapid discovery of many mutations associated with human disease. For neurodevelopmental disorders like Intellectual Disability (ID), there are now over 700 known causative genes. Stemming from this tsunami of new information is an increased need to understand the function of these genes in a relevant biological context. Among the 700+ known ID genes, there are several biological processes that are over-represented. This includes chromatin modifiers and epigenetic regualtors, which affect gene expression through biochemical modifications that do not directly alter the DNA sequence. My lab is focused on understanding the role of chromatin regulation in neurons. This project focuses on a specific chromatin remodeling complex, known as SWI/SNF, which is one of the most overrepresented complexes in ID. My lab has initiated a systematic analysis of SWI/SNF components in regulation of learning and memory in Drosophila. The high evolutionary conservation of this complex allows us to use flies to investigate the role of all 15 SWI/SNF subunits in neuron development and function. Our initial studies have identified a role for SWI/SNF subunits in development of specific brain regions that are required for memory. The main aims of this project are: (1) To investigate whether SWI/SNF complexes also play a role post-development, in adult-specific processes involved in learning and memory. (2) To identify SWI/SNF target genes that are important in the regulation of learning and memory. We use a multidisciplinary approach that combines spatiotemporal genetic manipulation, with high-throughput behaviour and cell-type specific genomics. These studies will begin to elucidate the role of the SWI/SNF complex in regulation of neuron development and function. This is a critical starting point toward understanding the human neurodevelopmental disorders associated with mutations in genes encoding SWI/SNF complex members.