SFARI | Topic: Molecular Mechanisms

Network activity and translational regulation in SHANK2 ASD neurons

Ellis and Martinez-Trujillo will explore the effects of SHANK2 mutations on protein translation and network connectivity in iPSC derived neurons.

Restoration of a splicing regulatory network commonly disrupted in autism

Blencowe will identify and characterize small molecules to rescue activity-dependent neuronal microexon splicing, providing a potential therapeutic strategy for autism.

Uncovering Trio’s role in autism spectrum disorder

Dysregulation of glutamatergic neurotransmission is believed to contribute to the development of autism spectrum disorder (ASD). Bruce Herring’s laboratory recently identified a hotspot of ASD-related de novo mutations in the glutamatergic synapse regulatory protein Trio. Herring’s team now aims to precisely characterize the impact these ASD-related Trio mutations have on glutamatergic synapse function and behavior.

Mechanistic studies of the interaction between Shank3 and CaMKIIα

Zhang aims to provide an atomic resolution structure of the Shank3:CaMKIIα complex and to understand the functional effects of activity and Shank3 ASD mutations on this complex.

Exploring calcium signaling defects in a mouse model of 16p11.2 deletion

Panagiotakos and her lab will use the 16p11.2 mouse model to explore how alternations in calcium signaling influence the function of neural stem cells and contribute to disease phenotypes.

The neuronal reprogramming factor and autism-associated gene Myt1l

The goal of this research project is to better understand the functions of Myt1l during normal embryonic brain development. As part of their genetic approach, Marius Wernig and Thomas Südhof will primarily focus on heterozygous mutant cells since the heterozygote condition is more similar to what is found in individuals with autism.

Molecular mechanisms of sensory transduction in the gut

Individuals with autism frequently experience visceral pain, constipation and diarrhea, but the mechanisms underlying such gastrointestinal symptoms are poorly understood. In the current project, David Julius’ laboratory is focused on delineating the properties of enterochromaffin cells, the serotonin-producing epithelial cells of the gut that detect noxious agents, communicate with sensory nerve fibers and contribute to visceral pain

Elucidating the signaling pathways involved in autism spectrum disorder

By integrating in vitro, ex vivo and in vivo techniques, Ori-McKenney will provide insight into how MNB/DYRK1a contributes to autism.

Brain protein networks perturbed by autism risk genes

This project aims to develop computational technologies to model human protein-protein interaction networks that are perturbed in autism.

Mouse Cntnap2 and human CNTNAP2 ASD alleles cell autonomously regulate PV+ cortical interneurons.