SFARI

Viral infection during pregnancy raises the risk of autism in the offspring, suggesting a connection between the maternal immune system and fetal brain development. Paul Patterson of the California Institute of Technology and his colleagues have successfully modeled this scenario in mice. In collaboration with David Amaral’s group at the University of California, Davis, they plan to extend these studies to non-human primates, which are socially and physiologically more similar to humans.

Genetic studies have linked several new genes to increased risk of autism. The challenge, however, is in understanding how mutations in these genes disrupt neural development and cause the disorder. Ted Dawson and his colleagues at Johns Hopkins University plan to undertake this task for the signaling protein known as the MET receptor.

Many children with autism have enlarged brains, often caused by an abnormally high density of neurons in the forebrain. Steven McKnight at The University of Texas Southwestern Medical Center and his colleagues hypothesize that defects in the NPAS1 gene, which acts as a brake on the creation of neurons in the developing brain, predispose individuals to autism.

Four independent studies have uncovered different autism-associated variants in the gene contactin­associated protein-like 2 (CNTNAP2), making this gene the first to have multiple variants associated with autism. The striking pervasiveness and diversity of the variants suggest that CNTNAP2 plays a crucial role in autism, leading Aravinda Chakravarti and his colleagues to embark on a detailed study of the gene.

Ventola will investigate oxytocin effects on behavioral intervention measures in individuals with autism, assessing neuroimaging, eye tracking and behavioral outcomes.

Portera-Cailliau and O’Donnell will study neural responses to tactile stimuli in fragile X syndrome mice to test whether sensory representations are varying and unstable over time.

Mitra will develop a novel methodology to analyze the transcriptional networks of genes involved in ASD and assign these genes into shared molecular pathways.

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.

Polimanti will use genetic- and brain-imaging approaches to understand the relationship between positive selection for common ASD risk alleles and cognitive abilities in affected and unaffected individuals.

Stessman aims to use human cell lines engineered to express patient mutations to determine how these genes contribute to disease etiology, particularly during early development of the human brain. These cell lines will also be a useful tool for therapeutic development in the future.