Project Detail
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Office of Autism Research Coordination (OARC) logo

Using zebrafish and chemical screening to define function of autism genes  

Roughly one percent of cases of autism are associated with deletions within a single region of chromosome 16, which contains nearly 30 genes. It is unclear which, and how many, of these genes are crucial in this association. Hazel Sive and her colleagues plan to determine which of these genes regulate brain development in zebrafish, in order to identify the genes that may contribute to the development of autistic spectrum disorders. Zebrafish are extremely valuable for many reasons: fish embryos develop rapidly, allowing rapid assays; they develop outside the mother, making observation of early stages simple; they are transparent, allowing analysis of brain development at a single-cell resolution in the living embryo; and both genetic and molecular screens can be readily performed to identify important genes. Of the 30 genes in the autism-associated region of chromosome 16, at least 25 have clear homologs in zebrafish. Many of these genes are expressed in the brain, including those that may regulate intracellular signaling pathways, brain activity and gene expression. In collaboration with Mark Daly of the Broad Institute, Sive plans to reduce the function of these genes using antisense oligonucleotides, which inhibit maturation of the messenger RNA (mRNA) corresponding to each gene. The researchers then plan to identify genes required for the formation of normal brain structure or neurons, and assess interactions between genes in this interval by simultaneously inhibiting the function of two or more genes. Sive then plans to work with collaborator Steven Haggarty of the Broad Institute to look for small molecules that can reverse brain phenotypes. Project Status
ONGOING

2009

Funder Simons Foundation
Fiscal Year Funding $395,496.50
Project Number 95091
Principal Investigator Sive, Hazel
Received ARRA Funding? No
Strategic Plan Question Question 4: Which Treatments And Interventions Will Help? (Interventions)
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 4SB. Standardize and validate at least 20 model systems (e.g., cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012. IACC Recommended Budget: $75,000,000 over 5 years.
Federal or Private? Private
Institution Whitehead Institute for Biomedical Research
State/Country Massachusetts
Web Link 1 Using zebrafish and chemical screening to define function of autism genes (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Using zebrafish and chemical screening to define function of autism genes | $399,999.00 | 2010 | 95091
Using zebrafish and chemical screening to define function of autism genes | $390,993.00 | 2008 | Project number unavailable