Innate Immune System Impact Request for Applications (closed)
The Simons Foundation Autism Research Initiative (SFARI) seeks to improve the diagnosis and treatment of autism spectrum disorders by funding innovative research of the highest quality and relevance.
Objective of the Innate Immune System Impact Award
Grants awarded through this Request for Applications (RFA) are intended to advance our understanding of the impact of activation of the innate immune system on behavioral, circuit, synaptic and neuronal functions in order to understand the consequences of infection and immune activation on autism-related behaviors.
To this end, we seek applications for investigations of the impact of physiologically relevant activation of the innate immune system on behavioral, circuit, synaptic and neuronal functions in animal models of autism. SFARI especially encourages applications that address either of the following two issues:
(1) Effects of activation of the maternal innate immune system on embryonic central nervous system development in genetic models of autism and controls. How do fetal genetics and maternal innate immune activation interact to affect postnatal autism-related phenotypes, and what are the mechanisms through which they interact?
(2) Effects of activation of the innate immune system in genetic autism models and adult controls. How does innate immune activation affect behavioral, circuit, synaptic and cellular function in these genetic models and in controls? What are the roles of cytokine signaling, fever, immune cell activation and other effectors on these functions?
Characterization of innate immune system effects on neural function and behavior
Studies have suggested that maternal viral infections are risk factors for autism during prenatal development1-4. Other studies have suggested that acute activation of the innate immune system and/or fever have beneficial effects in affected individuals5, 6. Research to address the molecular and cellular changes within the brains of genetic models of autism that alter synaptic, circuit and behavioral functions is needed to deepen our understanding of the interactions between genetics and innate immune system activation.
To address limitations in current knowledge, we request proposals that strive to understand the links between the innate immune system, brain function and autism-related behaviors in genetic models of autism and controls. Priority should be given to behaviors for which circuits are reasonably well established. Experiments should include physiologically relevant activation/inhibition of the innate immune system in animal models of autism and should focus on neuronal, synaptic and circuit function. Inclusion of behavioral assessments of clear relevance to human autism spectrum disorders will strengthen proposals. The use of culture or other reduced preparations must be convincingly justified for relevance.
In order to find commonalities and distinctions between models, experiments should be carried out in two or more rodent models of autism, with a view to future inclusion of additional models. Relevance of experiments to human autism disorders should be justified. We expect that competitive applications will primarily rely on a laboratory’s established technical capabilities and expertise.
We encourage proposals for collaborative projects between neuroscientists and immunologists.
Potential applicants are strongly advised to familiarize themselves with the projects in this area that SFARI currently supports and to think about how their proposals might complement existing grants.
Which autism models?
SFARI prioritizes animal models with strong construct validity based on human genetic studies of autism. To this end, SFARI is currently funding systematic behavioral testing on select mouse models and increasing their availability to the broader scientific community through The Jackson Laboratory in Bar Harbor, Maine. Investigators are strongly encouraged to consider using this resource when developing their experimental plans. Given the breadth of knowledge about the genetics of autism, SFARI expects and encourages most applicants to focus on genetic autism and/or innate immunity mouse models, but other models may be proposed if the application contains a compelling rationale based on strong evidence from human studies.
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 national residence requirements.
If the proposal includes investigators at more than one site, all investigators should have demonstrated prior success in similar collaborations.
Funding period and budget
The grant period is for three (3) years. Continued funding is possible, when justified by scientific progress. During this initial three-year period, SFARI plans to commit up to $1 million annually to support projects funded as a result of this RFA.
Applications should include the following:
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. The investigative team should include members with strong expertise in the physiological recordings and behaviors they propose in their application.
3. Current and pending support for Principal Investigator(s) and Key Collaborators.
4. Budget. While there are no budget caps on the individual applications, budgets will strongly factor into the competitiveness of an application. Budgets of more than $250,000 annually will need convincing justification. It is unlikely that SFARI will make an award larger than this amount. Proposals should include a realistic budget sufficiently detailed for evaluation of needed resources. SFARI will work closely with investigative teams with competitive applications to arrive at a suitable budget. Indirect costs are limited to 20 percent of the modified total direct costs (see SFARI policies).
Applications with multiple Principal Investigators from different institutions that would like to be paid separately must include a signed budget template and budget justification for each Principal Investigator’s 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.
5. Research environment and resources. Investigators should demonstrate access to appropriate resources for high-capacity data collection and analysis, although SFARI will work with awarded investigative teams to provide additional informatics support as needed.
6. Data-sharing plan. The plan should include sharing of raw and analyzed data. SFARI will work closely with awarded investigative teams to ensure that the final plan includes timely dissemination of data with reasonable embargo provisions.
For more details, see the Instructions document, which is available for download in the proposal attachments section of proposalCENTRAL.
The deadline for full proposal submission is 3 March 2014, 5 p.m. Eastern. No extensions will be given. If you have any difficulties, please contact [email protected].
Competitive applications will receive external peer review. SFARI will make final funding decisions; notification of award is expected by 1 July 2014, with funding expected to begin 1 August 2014.
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.
1. Patterson P.H. Behav. Brain Res. 204, 313-321 (2009) PubMed
2. Atladóttir H.Ó. et al. Pediatrics 130, e1447-1454 (2012) PubMed
3. Garay P.A. et al. Brain Behav. Immun. 31, 54-68 (2013) PubMed
4. Hsiao E.Y. et al. Proc. Natl. Acad. Sci. USA 109, 12776-12781 (2012) PubMed
5. Mehler M.F. and D.P. Purpura Brain Res. Rev. 59, 388-392 (2009) PubMed
6. Curran L.K. et al. Pediatrics 120, e1386-1392 (2007) PubMed