Finding Down Syndrome Cell Adhesion Molecule (DSCAM) Protein Interactions in Pathways of Neuronal Development

Down Syndrome cell adhesion molecule (DSCAM) is a transmembrane protein that has a significant role in proper neurodevelopment by promoting self-avoidance in neurons. This project aims to identify proteins that interact with DSCAM in the mouse brain by using a library of plasmids. The plasmid library was tested for proteins that interact with the C-terminus end of DSCAM in Brewer’s yeast (S. cerevisiae). By using the bait and prey method from a yeast two-hybrid system, mouse brain proteins were tested for true interaction with DSCAM. Proteins that interact with DSCAM allow the yeast to produce their own leucine, which aids in the growth of the yeast on selective media. Proteins that have been identified as possible protein interactors include COX5B, NEFL, ELAV1, and SOD1, among others. By identifying interactions between unknown proteins and DSCAM, we will be better able to map out the protein interactions that lead to the proper development of the brain

Unravelling Genetic Determinants of Synaptic Formation in the Mammalian Visual System

Blinding diseases such as age-macular degeneration and glaucoma are common causes of vision loss and occur in 2-15% of the population. A detailed understanding of visual system organization is a limiting factor in developing treatments for such disorders. Genetic blinding diseases are studied to understand visual system organization and diseases. Stationary night blindness, is caused by mutation in the Dscaml1 gene. Dscaml1 encodes for the protein, Down Syndrome Cell Adhesion Molecule-like 1 (DSCAML1), which plays a role in organization of cells critical for night vision. In a previous study we used electron micrographs to visualize the cellular organization of rod bipolar cells (RBCs) in the synaptic pathway within the mouse retina, an accessible model for human diseases. We found an increased number of dendrite terminals that do not contact rod photoreceptors in the absence of DSCAML1. This project focuses on using immunohistochemical (IHC) techniques to compare the development of the synaptic pathway at multiple post-natal time points in three genotypes. It is predicted that the loss of DSCAML1 results in termination of the pathway between the RBCs and dendrites instead of a delay in formation. This study is intended to guide clinicians seeking interventions for people with similar disorders