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This RFA sought proposals that aimed to comprehensively analyze the behavior of mouse models that have been generated with targeted genetic mutations based on strong human genetic evidence implicating them in autism spectrum disorders. The program prioritized a small number of mouse models including 16p11.2 chromosomal segment deletion, Cntnap2-/- and Shank3b-/-. To maximize the ability to make direct comparisons among mouse models, this request sought applications for systematic, rigorous and scalable analyses of behavioral phenotypes across multiple mouse models. Investigators were expected to test at least three genetic models in the same background strain (C57BL/6). In addition, investigators needed to analyze the behavior of one of the selected autism mouse models in a different genetic background, such as a hybrid background from two inbred strains. The data produced in this effort was made available to the research community.

This request for applications (RFA) was intended to advance understanding of the circuit basis for behavioral and cognitive alterations relevant to autism spectrum disorders (ASD). The goal was to determine the downstream consequences of autism-associated genetic perturbations on neural circuitry, with an emphasis on how collections of neurons operate in concert during autism-relevant behaviors. The program sought applications for investigations of neural circuits in awake, behaving rodent models of autism. SFARI worked closely with awarded investigative teams on all major aspects of the project, including selection of rodent models, data coordination and dissemination. Priority was given to projects focused on behaviors for which the underlying circuits are reasonably well established, with experiments including electrical or optical multi-neuronal recordings within microcircuits or macrocircuits. Studies needed to be centered on brain activity in awake, behaving animals. Recordings needed to be carried out in two or more rodent models of autism to find commonalities and distinctions between models. Competitive applications were expected from labs proposing to apply their established technical capabilities to the study of autism rodent models.

Grants awarded through this RFA were intended to advance our understanding of the genetic basis of autism, and in particular, to begin to assess genetic variants conferring risk in non-coding regions and in coding regions of the genome that may be less accessible to whole-exome sequencing. The program partnered with the New York Genome Center to sequence whole-genomes from 500 Simons Simplex Collection quartet families (2,000 genomes at 30X sequence coverage). Investigators were encouraged to develop innovative and efficient ways to analyze whole-genome sequencing data to identify de novo and inherited mutations, CNVs not identified by WES, non-coding variants associated with autism risk, and mitochondrial DNA variants. The program particularly sought multidisciplinary approaches and collaborations between investigators with complementary expertise in analyzing large genomic datasets.

The Explorer Awards Request for Applications (RFA) was designed to enhance SFARI's existing support of autism research by providing timely resources to enable high-risk/high-impact, exploratory experiments relevant to their mission. The program supports exploratory experiments that will strengthen hypotheses and lead to the formulation of competitive applications for subsequent larger-scale funding by SFARI or other organizations. A deeper understanding of the mechanisms underlying autism spectrum disorders or potential therapeutic approaches requires investigation at multiple levels, including but not limited to studies focused on gene discovery, molecular mechanisms, circuits, anatomy, and cognition and behavior. The program especially encouraged applications from investigators who are new to the field of autism, but who have expertise that could be brought to bear on this complex disorder. Applications were considered on a rolling basis, with a response time as early as 30 days.

The goal of the Pilot Progression Award is to provide continuing support for projects initiated during SFARI Pilot awards that have advanced significantly and produced insights that justify an extension. This mechanism is intended for projects that generated promising preliminary data during their initial Pilot funding and remain relevant to autism spectrum disorders research but may not yet be suited for funding from other sources like NIH. The Pilot Progression Award is not meant to provide additional time and budget to support the completion of original Pilot aims, but instead to support extensions or expansions of these projects, such as expanding the number of genetic models studied, moving to the next logical level of mechanistic understanding, or broadening experiments to include additional behaviors or brain regions. Applicants are encouraged to provide evidence of attempts to obtain funding for proposed work from other sources. Applications will be reviewed first by the SFARI science team, and then a subset will be peer-reviewed by an external review panel.