Analysis of Simons VIP Biospecimens Request for Applications

SFARI mission

The mission of the Simons Foundation Autism Research Initiative (SFARI) is to improve the diagnosis and treatment of autism spectrum disorders by funding innovative research of the highest quality and relevance.

Objective of this award

The Simons Variation in Individuals Project (Simons VIP) comprises a large cohort of individuals with a deletion or duplication of chromosomal segment 16p11.2 (approximately 100 deletion and 100 duplication carriers) ¹. A wealth of phenotypic (behavioral, neurological and neuroimaging) data has been collected from these individuals and their families. The data collected so far emphasize significant phenotypic variability: About 20 percent of deletion and duplication carriers meet strict criteria for an autism diagnosis; many other carriers have other neuropsychiatric diagnoses, including a high rate of language difficulties².

We anticipate that further analysis of biospecimens collected from the individuals in the Simons VIP will help explain some of the heterogeneity in phenotype.

This RFA seeks proposals that take advantage of the unique combination of biospecimens and rich phenotypic information collected by the Simons VIP. Although SFARI is open to many different approaches, we will likely give priority to those that aim to accomplish a comprehensive characterization of RNA expression differences and correlate such expression patterns with phenotypes. Furthering the ability to include genomic analysis would be an additional strength. The data produced in this effort will be made available to the research community with minimum delay and thus will be a valuable resource for all researchers.

Simons VIP biospecimens

In addition to an extensive battery of psychological tests, neurological exams, growth and dysmorphology measures, structural and functional brain MRI and MEG, blood was collected from each study participant. Cultured fibroblasts are also available for roughly 30 percent of the participants. Lymphoblastoid cell lines exist or could be produced as needed. Additionally, we have the option of creating iPS cell lines for each participant, should the demand exist. For more information regarding available biospecimens, please visit the Simons VIP Overview Statistics page. If you do not currently have a SFARI ID, you will be directed to request one; you will need it to access the statistics.

Experimental plan

We anticipate that proposals may differ among applications because of the varying expertise and resources of the investigative teams. We will give priority to proposals that include:

1. RNA sequencing and quantification
2. A detailed plan for the correlation of RNA expression patterns and phenotypes
3. A rationale for the use of specific cell types (fibroblasts, lymphoblastoids, iPS-cell-derived neurons, etc.)
4. A detailed rationale for how to prioritize sample selection (e.g., initial focus on phenotypic subgroups, deletion/duplication carriers and family member controls. Please review the available information on medical history and phenotyping data at SFARI Base. If you do not currently have a SFARI ID, you will be directed to request one upon logging in.)

Also desirable but not required is the capacity to integrate exome sequencing data, which may be available from other sources, into the correlation analysis.

Eligibility and collaboration

All applicants and key collaborators must hold a Ph.D., M.D. or equivalent degree and have a faculty position or the equivalent at a college, university, medical school or other research facility. Applications may be submitted by domestic and foreign nonprofit organizations; public and private institutions, such as colleges, universities, hospitals, laboratories, units of state and local government; and eligible agencies of the federal government. There are no citizenship or country requirements.

If data collection will be performed at more than one site, investigators should have demonstrated prior success in reproducing results across sites.

Application requirements

1. Narrative, not exceeding six (6) pages (excluding references and figures). Proposals should include specific aims, background relevant to the application, significance of the proposed studies, preliminary results, experimental design, pitfalls and alternative strategies, relevance to autism, and a timeline with milestones.
2. Biosketches for Principal Investigator(s) and Key Collaborators.
3. Current and pending support for Principal Investigator(s) and Key Collaborators.
4. Budget. There is no budget cap, although indirect costs are limited to 20 percent of the modified total direct costs (see SFARI policies). Budget will strongly factor into the competitiveness of an application. Therefore, proposals should include a realistic budget sufficiently detailed for evaluation of needed resources. SFARI will work closely with investigators with competitive applications to arrive at a suitable budget. In addition to the award amount, SFARI will cover the cost of currently available biospecimens. SFARI also may cover the creation of biospecimens that are currently unavailable (e.g., iPS cells), under the condition that this resource will be made available for distribution to other researchers.

Applications with multiple Principal Investigators (PIs) from different institutions that would like to be paid separately must include a signed budget template and budget justification for each PI institution. Applications with subcontracts must include a budget and budget justification. The budget template and budget justification are available for download in the proposal attachments section of proposalCENTRAL’s full application.

1. Research environment and resources. Investigators should demonstrate access to appropriate resources for high-capacity data collection and analysis. SFARI will work with awarded investigative teams to provide additional informatics support as needed.
2. Renewable reagents and data-sharing plan. The plan should detail how renewable resources will be stored and distributed to other researchers. It should also include sharing of raw and analyzed data. SFARI will work closely with investigators to devise a sharing plan.

Application deadline

The deadline for full proposal submission is 21 June 2013. Competitive applications will receive external peer review. SFARI will make final funding decisions; notification of award is expected in early October 2013 at the latest, with funding expected to begin no later than 1 November 2013.

Instructions for submission

Applications must be completed electronically and submitted using forms provided at proposalCENTRAL. Please log in as an applicant, scroll to “Simons Foundation” and click on the program.

Contacts

Scientific inquiries:
sciencerfa@simonsfoundation.org
646-654-0066

Administrative inquiries:
grants@simonsfoundation.org
646-654-0066

proposalCENTRAL:
pcsupport@altum.com
800-875-2562

References

1: Simons VIP Consortium Neuron 73, 1063-1067 (2012) PubMed

2: Zufferey F. et al. J. Med. Genet. 49, 660-668 (2012) PubMed