Date of Award
Director of Thesis
Dr. Deanna Smith
Dr. Fabienne Poulain
LIS1 is a protein, particularly concentrated in the brain, that is important in regulating the movement and transport capabilities of dynein. Dynein is protein that can move along pathways in the cell, carrying various cellular components and also helping brain cells migrate. These two proteins are crucial during the development of the nervous system, and mutations in them can lead to lissencephaly, a disorder in which the brain does not form properly. This disease causes patients to develop cognitive-motor defects and seizures that can lead to early death. While all previously identified mutations in LIS1 are known to cause lissencephaly, we have identified a patient with a LIS1 mutation, called K351R, that instead presents with Autism Spectrum Disorder (ASD). ASD is a disorder of varying severity that comes with social and communicative difficulties.
In this thesis, I created the K351R mutation in a LIS1 model and inserted it into cells to see if the mutation changed the functionality of LIS1 and its regulation of dynein and to determine if this mutation has the potential to affect developmental processes that may lead to ASD. The experiment found that the K351R mutation of LIS1 stimulates the movement of dynein along cell pathways when compared to the WT LIS1. These results support pursuit of more research to further discover the connection between this mutation and improper development of the brain and nervous system.
Slovensky, John A., "The Effects of a New Mutation in LIS1 and Its Potential Role in Autism Spectrum Disorder" (2020). Senior Theses. 348.