Neurological disorders such as Alzheimer?s disease, autism spectrum disorders (ASD), and schizophrenia impact important cognitive processes and behavior. While the symptoms of these severe diseases vary, they share disruptions in synapse development or spine formation4. Dendritic spines are small, dynamic, post- synaptic protrusions on neurons that respond to changes in presynaptic activity1. Although spine dynamics have been well studied, very little is known about the genes involved in spine formation and maintenance. Recently, my laboratory discovered spiny projections on a group of GABAergic neurons in Caenorhabditis elegans. Using C. elegans as a model system, the goal of this project is to dissect cellular and molecular components important for dendritic spine formation and maintenance. Specifically, in the first aim, I will define the structural dynamics, and cellular components that drive development and maintenance of these spine-like protrusions. In my second aim, I will utilize findings from a genome-wide genetic screen to investigate the role of unc-14, a cargo adaptor protein in these spine-like structures, and elucidate the molecular identity and functions of 2 additional spine mutants, 21-6-1K and 31-6-1G2. Given the strong homology between C. elegans and mammalian genes, I expect that my approach will identify conserved mechanisms underlying dendritic spine formation. These studies will address fundamental questions about dendritic spine biology and offer valuable training in microscopy, genetics, and molecular approaches that will advance my scientific development and provide a foundation for my future scientific endeavors.
Disruptions in post-synaptic dendritic spines have been implicated in a variety of neurological diseases such as Alzheimer?s disease, autism spectrum disorders, and schizophrenia. My proposed work will unveil cellular and molecular underpinnings of spine-like protrusion formation and maintenance, using the model system Caenorhabditis elegans. This research will help shape the treatment of diseases and disorders with abnormal dendritic spines.
