Declan Murphy and Will Spooren will lead the Autism Innovative Medicine Studies-2-Trials (AIMS-2-Trials), a large-scale collaborative research project that involves 48 partners across 14 countries. The study aims to develop a better understanding of the biological bases of ASD, develop biomarkers and testing potential drug treatments of the disorder.
Caroline Robertson plans to assess alterations in binocular rivalry in two distinct genetic subgroups of autism: fragile X syndrome and 16p11.2 deletion syndrome. Findings from these studies will lead to a better understanding of how sensory-perception deficits relate to specific subtypes of autism and will help to stratify individuals based on therapies they might be likely to respond to.
The rat is a more sociable species than the mouse, and a larger spectrum of behavioral assessments are available to researchers. Using outbred rat 16p11.2 deletion and duplication models recently developed in his laboratory, Yann Herault will assess whether these animal models recapitulate the mouse phenotypes. Additional communication and sociability phenotypes will also be investigated.
Matthew Goodwin will further develop and evaluate software tools for the automated analysis of ambulatory electrodermal activity — a measure of sympathetic nervous system arousal — to accelerate the effective use of such measures in clinical trials research involving individuals with autism and related neurodevelopmental disorders.
Many genes implicated in autism encode proteins at synapses, the connections between neurons. These proteins include the neuroligin-neurexin complex and the PSD95-SAPAP-SHANK complex at synapses that release the neurotransmitter glutamate[ref]Ting J.T. et al. Ann. Rev. Neurosci. 35, 49-71 (2012) PubMed[/ref].
Ellis and Martinez-Trujillo will explore the effects of SHANK2 mutations on protein translation and network connectivity in iPSC derived neurons.
Ginty will define the mechanisms of aberrant touch sensitivity in mouse models of ASD and in individuals with ASD, and will translate these findings into possible therapeutics.
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.
Bateup will use genetic mouse models of ASD to investigate the idea that synaptic alterations in the striatum are central to the inflexible behaviors observed in ASD.
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.