Guillermo Sapiro, in collaboration with Geraldine Dawson, seeks to develop and validate automatic, objective and quantitative measurements of social communicative and motor behaviors based on visual attention, affective facial expressions, vocalizations and head movements that can serve as feasible, reliable and sensitive outcome measures in autism clinical trials.
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.
To facilitate studies by laboratories with specialized expertise in neural development and brain function, Harold Burgess will create zebrafish lines with individual mutations in five high-confidence ASD risk genes and will provide them to the research community as an unrestricted resource.
Nael Nadif Kasri will assess differences in neuronal network activity and transcriptional profiles in neural cells derived from induced pluripotent stem cells from individuals with syndromic forms of ASD, building a phenotypic map based on network activity and cellular profiles. These phenotypic maps will aid in the dissection of the underlying cellular and molecular mechanisms involved in distinct forms of ASD.
Gordon Fishell and Jordane Dimidschstein will combine human genetic data with large-scale transcriptomic and epigenetic analyses to assess how alterations in autism risk genes affect biological processes occurring within GABAergic and cholinergic neuronal populations during the early stages of fate specification.
Ellen Hoffman and Ted Abel aim to compare findings from high-throughput behavior-based screens in zebrafish models of ASD risk genes to mouse behavioral phenotypes in order to elucidate the cellular and circuit-level effects of drug candidates that suppress ASD-relevant behaviors in both systems. The results are expected to identify novel pharmacological targets for further evaluation in ASDs.
Alterations in FOXP1 are associated with ASD and mouse models suggest that Foxp1 is important for striatal development and function. Genevieve Konopka and Jay Gibson will use a combination of molecular and electrophysiological methods to investigate how cell-type specific deletions of Foxp1 affect striatal cell fate, survival and function in mice.
A seven-laboratory consortium, headed by Kurt Haas, has established a platform to measure the impact of large numbers of ASD missense variants on protein function in multiple model systems, making best use of rapid high-throughput screening assays and slower high-sensitivity assays to examine the effects of these mutations on vertebrate neuronal development.
In this study, Carolyn Bridgemohan and colleagues assessed the feasibility of using platelet serotonin and urinary melatonin levels as biomarkers in children with ASD, including evaluating potential associations between these biochemical measures with physical, behavioral and cognitive profiles.
Jun Huh will examine human-derived bacteria that can colonize the guts of pregnant mice to identify bacteria that can promote anti-inflammatory responses. Such factors could help to prevent the development of brain pathologies and behavioral phenotypes relevant to autism in offspring that can be triggered by uncontrolled inflammatory activity during pregnancy.