Project Detail
Interagency Autism Coordinating Committee (IACC) logo
Office of Autism Research Coordination (OARC) logo

Role of TSC/mTOR signaling pathway in autism and autism spectrum disorders  

For years, autism has been noted in individuals with tuberous sclerosis, leading researchers to speculate that the two disorders may develop after troubles in the same biological pathway. Vijaya Ramesh and her colleagues at Massachusetts General Hospital are pursuing this lead by investigating whether genes linked to tuberous sclerosis are also associated with autism spectrum disorders. The TOR pathway, which is named after a key protein that receives information on the cell surface, controls the growth of many cells and regulates the connections neurons make with each other. Mutations that remove regulators of the TOR pathway are associated with tuberous sclerosis. Ramesh hypothesizes that disruptions in this pathway may also cause the neuronal abnormalities that lead to autism. Ramesh and her colleagues are examining the genes of several components of the TOR pathway, looking for rare variations that are associated with autism. By narrowing their focus, the researchers will be able to analyze more samples drawn from the Simons Simplex Collection, with a greater attention to detail in the candidate genes. Once one mutation is linked to autism, the researchers can try to find the mutation among more people with autism to make the correlation stronger. The team will also perform assays in cultured neurons to see how the mutations affect TOR pathway activity. The investigators have adopted a two-tier pooling strategy wherein 10 DNA pools each of 300 patients (30 samples per pool) and 600 control samples (60 samples per pool) have been assembled. After completing sequencing of the 300 patient samples and 600 controls, the researchers plan to identify rare variations that are specific to autism samples. In future studies, they aim to confirm the identified variants in additional samples and validate these variants in functional assays using cultured neurons. This work will potentially identify novel pathways and strategies for autism treatment. Project Status


Funder Simons Foundation
Fiscal Year Funding $83,403.00
Current Award Period 2008-2010
Project Number 95345
Principal Investigator Ramesh, Vijaya
Received ARRA Funding? No
Strategic Plan Question Question 3: What Caused This To Happen And Can This Be Prevented? (Causes)
Subcategory Genetic Risk Factors
Strategic Plan Objective Green dot: Objective has greater than or equal to the recommended funding. 3LB. Identify genetic risk factors in at least 50% of people with ASD by 2014. IACC Recommended Budget: $33,900,000 over 6 years.
Federal or Private? Private
Institution Massachusetts General Hospital
State/Country Massachusetts
Web Link 1 Role of TSC/mTOR signaling pathway in autism and autism spectrum disorders (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
History/Related Projects Role of TSC/mTOR signaling pathway in autism and autism spectrum disorders | $172,824.50 | 2009 | 95345
Role of TSC/mTOR signaling pathway in autism and autism spectrum disorders | $178,843.00 | 2008 | Project number unavailable