Project Detail
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Office of Autism Research Coordination (OARC) logo

Aberrant synaptic function caused by TSC mutation in autism  

Dr. Sulzer and his colleagues hypothesize that cortex overgrowth in early development, a possible cause of autism, can result from defects in the tuberous sclerosis pathway, which normally keeps neuronal growth under control. In a healthy individual, the tuberous sclerosis pathway promotes macroautophagy, a normal process by which cells break themselves down to restrict their growth. Sulzer and colleagues believe mutations in the tuberous sclerosis genes disrupt the macroautophagy pathway in neurons, allowing them to grow out of control in the brain. The researchers plan to study macroautophagy in experimental mice with inactivated tuberous sclerosis genes. From a biochemical perspective, they will ascertain whether dysregulation of mTOR — a protein that inhibits macroautophagy but is normally kept in check by the tuberous sclerosis proteins — results in overgrowth of neurons in the mice. The researchers also plan to assess whether the mutant mice have different levels of neuronal activity in the cortex than do healthy mice. Finally, the researchers plan to test whether the drug rapamycin, which inhibits the mTOR protein, can reestablish normal levels of macroautophagy in the mutant mice. Project Status


Funder Simons Foundation
Fiscal Year Funding $75,000.00
Current Award Period 2008-2011
Project Number 95505
Principal Investigator Sulzer, David
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Molecular Pathways
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 2SD. Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g. Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. IACC Recommended Budget: $9,000,000 over 5 years.
Federal or Private? Private
Institution Columbia University
State/Country New York
Web Link 1 No URL available.
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects Aberrant synaptic function caused by TSC mutation in autism | $173,726.00 | 2009 | 95505
Aberrant synaptic function caused by TSC mutation in autism | $0.00 | 2011 | 95505