Regulating Small GTPase Prenylome by SmgGDS During Neuronal Development

Advancing understanding of how abnormal events in the brain during embryogenesis contribute to Autism Spectrum Disorder

Full Project Name:Regulation of the Small GTPase Prenylome by SngGDS During Neuronal DevelopmentPrincipal Investigator:Carol Williams, PhD, Pharmacology and ToxicologyCo-Investigator(s):Allison Ebert, PhD, Cell Biology, Neurobiology, and Anatomy
Cecilia J. Hillard, PhD, Pharmacology and Toxicology
Mark Distefano, PhD, University of MinnesotaAward Amount:$250,000

Award Date

July2021

Project Duration:36 months

Project Summary:

An increasing number of children are being diagnosed with autism spectrum disorder (ASD), a developmental disorder that results in a wide range of behavioral, intellectual, and social disabilities. ASD is caused by a group of neurodevelopmental disorders that arise from abnormal development of the brain during embryogenesis. Understanding the factors that promote normal neurodevelopment and identifying new approaches to prevent or correct neurodevelopmental abnormalities may provide new therapeutic strategies for ASD.

Through this award, investigators will aim to advance understanding of how abnormal events that occur during brain development contribute to ASD by testing whether a new group of compounds can be used to decrease the occurrence of abnormal events in the brain.

Outcomes & Lessons Learned:

Detected that the study protein, SmgGDS, undergoes changes as neurons develop
Confirmed that SmgGDS can be altered in developing neurons using experimental agents, which will be valuable tools for examining how manipulation of SmgGDS alters neuronal maturation
Designed and synthesized a new form of prenyl probe and tested the new probes for their efficiency in measuring the prenylome
Published a manuscript focused on the design, synthesis, and testing of the new prenyl probes developed through the project