Faculty Sponsor: Dr. Bryan Thurtle-Schmidt
The SLC6 protein family is essential for transporting amino acids, neurotransmitters, and osmolytes within the brain. Studies have shown that mutations within this family could cause obsessive compulsive disorder, autism, depression, alcoholism, Tourette’s syndrome, and schizophrenia. The purpose of this independent study was to help understand the mechanistic basis of the mutations. The investigation began by making homology models for all 19 proteins, mapping all mutations found via literature, modeling the mutations on the homology models, then analyzing the detrimental effects of the mutation. Our results identified mutational hot spots in transmembrane helix 7 and proximal to the ligand binding site. Additionally, the research cohesively organized all data concerning SLC6 mutations, which provides a framework for contextualizing their effects on transporter function. This work is important because it can be used as a roadmap to dissect the mechanistic basis of disease-causing mutations and thereby set the stage for the development of therapeutics.