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: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:24 months

Project Description Narrative:

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.

Project Updates:

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
Working to improve the techniques needed to analyze the prenylome in the brain
Designed and synthesized a new form of prenyl probe and currently testing these new probes for their efficiency in measuring the prenylome
Observed that findings support hypothesis that the SmgGDS 607:558 ratio plays a role in neuronal development