Autism Rat Models Consortium – Request for Applications

SFARI Mission

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

Background and Objectives

Grants awarded through this request for applications (RFA) are intended to capitalize on the rat as a model system to advance our understanding of the behavioral and circuit neuroscience mechanisms driving autism.

SFARI has supported the development of rats carrying mutations to high-confidence autism-related genes on the Long-Evans outbred genetic background (Charles River Laboratories). The genes include FMR1, ARID1B, CHD8, CNTNAP2, DYRK1A, NRXN1, SCN2A and GRIN2B. These same rat models are currently being evaluated through a comprehensive behavioral phenotyping pipeline established by the Simons Initiative for the Developing Brain (SIDB). Access to these models, as well their resulting data from the SIDB pipeline, are available to any qualified researcher.

To build upon these resources, SFARI recently convened a workshop to discuss strategies that might best exploit the advantages afforded by rat models and to specify recommendations for moving the field forward. Discussions at the workshop resulted in a number of insightful conclusions, as well as actionable recommendations for scientific and organizational priorities.

The current RFA is intended to begin implementing these workshop recommendations by supporting a consortium of investigators to collaboratively use SFARI autism rat models to examine the biological basis of complex behaviors and the underlying neural circuits relevant for autism.

Scientific Scope and Priorities

Proposals are expected to utilize SFARI rat models to conduct in-depth behavioral and/or circuit analyses to further understand mechanisms underlying autism. Competitive applications will utilize the rat’s advantages as both a highly trainable species and its innate capacity to express varied, complex behavior. We also encourage proposals that incorporate recent advances in computational ethology and high-resolution behavioral phenotyping.

SFARI recognizes the complementary insights gained from more constrained paradigms, for which the underlying neurobiology is relatively well understood, as well as more naturalistic paradigms, which facilitate the expression of the rat’s diverse behavioral repertoire. We welcome either type of experimental strategy, as long as the paradigms are species appropriate, address the proposed hypotheses and are interpreted within the biological constraints of the rat.

SFARI is interested in the diversity of relevant functional domains—from sensorimotor, to cognitive, to social/affective functioning. Regardless of the domain(s) of focus, the overarching framework should consider linking hypotheses from genes to behavior. For example, applications may broadly explore one or more of the following challenges in the autism field:

To better understand the circuit and behavioral consequences of known molecular/cellular disruptions caused by mutations in autism risk genes. A consensus picture has emerged that many autism risk genes cause early disruptions in the orderly timing and execution of neuronal differentiation^1,2,3,4,5. However, it remains unclear as to how these early cellular and molecular deviations result in changes in neural circuit function and behavior.

• We encourage proposals that are informed by molecular and cellular insights gleaned from other experimental model systems, such as the mouse, to examine the resulting impact on rat complex behaviors and circuit function. Proposals may include specific experiments to address whether reported cellular mechanisms/phenotypes in other model systems are conserved in the rat, in order to facilitate interpretation of observed phenotypes at the systems and behavioral levels. However, the majority of the grant application should focus on the analysis of behavior and/or systems-level circuit dynamics in SFARI rat models.

To better understand the role of development and compensation in driving the behavioral and circuit differences between mutant rat models and their controls. Despite its developmental origins, the role of behavioral and circuit development has been relatively understudied in model systems for autism.

• We encourage proposals that examine the developmental trajectory of behavioral and circuit phenotypes in autism rat models. These studies may include hypotheses about the role of biological compensation, ranging from cellular mechanisms to systems-level information processing.

Applicants are expected to use, but are not limited to using, SFARI rat models. They should consider the following criteria in selecting their models: (1) biological function of the gene, (2) reported biological phenotypes from other model systems with the same gene mutation and (3) phenotypic profiles of affected individuals with the same gene mutation. SFARI encourages applicants to utilize resources, such as SFARI Gene and Simons Searchlight as starting points for their literature review.

Organizational Framework

As recommended by the workshop, SFARI will facilitate coordination across funded projects through a research consortium. While the details are yet to be determined, these will include periodic meetings among funded investigators to discuss challenges and share research findings. We hope that these serve as organic collaborative opportunities, which could lead to parallel and overlapping approaches across several labs. Costs associated with attending any SFARI-initiated meetings will be covered separately by the Simons Foundation.

SIDB will also regularly update and provide consortium members full access to data obtained from their behavior phenotyping pipeline on the SFARI rat models. Pending availability, there may also be future opportunities for short sabbaticals at SIDB for research trainees/specialists to gain research experience/conduct explorative behavioral experiments with the autism rat resources and expertise available at the University of Edinburgh.

Investigators funded through this RFA are expected to work collaboratively as a research consortium. This includes actively contributing to the intellectual pursuits of the consortium and adhering to an open-science ethos by sharing protocols, data and reagents with other consortium members and SFARI throughout the grant period.

Level and Duration of Funding

Each lab may request a maximum of $300,000, inclusive of 20 percent indirect costs, for each year of funding over a period of two (2) to three (3) years. We welcome applications from individual labs, as well as collaborative applications of up to three (3) principal investigators (PI). Allowable Indirect costs to the primary institution for subcontracts are not included in the total budget threshold (see grant policies). We encourage investigators to take advantage of the flexibility in budget and duration, tailoring the scope of the award as appropriate for their specific aims. As with all SFARI-funded projects, it is at Simons Foundation’s discretion to modify final budgets as needed.

Progress will be critically evaluated at the end of each annual funding period before support for the upcoming year will be approved. Adherence to the open-science ethos of the research consortium will be an important consideration in yearly assessments.

Review Process

Applications will be evaluated by the SFARI science team, with a subset selected for further evaluation by an external review panel. Competitive applications will be invited to present their proposal to the SFARI science team and invited scientists.

Eligibility

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.

SFARI recognizes the importance of diverse viewpoints for scientific advancement. As such, SFARI encourages the inclusion of researchers who span career stages and groups historically underrepresented in science.

Applications may be submitted by domestic and foreign nonprofit organizations; public and private institutions, such as colleges, universities, hospitals, laboratories and units of state and local government; and eligible agencies of the federal government. There are no citizenship or country requirements.

Instructions for Submission

Applications must be completed electronically and submitted using forms provided at proposalCENTRAL. Please log in as an applicant, go to the grant opportunities tab, scroll to “Simons Foundation,” and click “Apply Now” for the “Autism Rat Models Consortium – RFA.” For assistance, please call 800-875-2562 or email [email protected].

Details concerning application requirements and submission can be found in our instructions or on proposalCENTRAL. If you have other questions, please review our FAQ.

Informational Sessions for Potential Applicants

To answer questions about this RFA, SFARI will hold an informational Zoom meeting on July 26, 2021 at 11 am EDT. Interested applicants can register here.

Our Commitment to Diversity, Equity and Inclusion

Many of the greatest ideas and discoveries come from a diverse mix of minds, backgrounds and experiences. The Simons Foundation is committed to grantmaking that inspires and supports greater diversity and inclusiveness by cultivating a funding environment that ensures representation of all identities and differences and equitable access to information and resources for all applicants and grantees.

The Simons Foundation provides equal opportunities to all applicants for funding without regard to race, religion, color, age, sex, pregnancy, national origin, sexual orientation, gender identity, genetic disposition, neurodiversity, disability, veteran status or any other protected category under federal, state and local law. The foundation also funds programs directed at supporting scientists from disadvantaged backgrounds or underrepresented groups, often working closely with professional societies and other funding agencies.

References

1. Khalfallah O. et al. Stem Cells 35, 374-385 (2017) PubMed
2. Suetterlin P. et al. Cereb. Cortex 28, 2192-2206 (2018) PubMed
3. Moffat J.J. et al. Sci. Rep.11, 3856 (2021) PubMed
4. Levy J.A. et al. Biol. Psychiatry Epub ahead of print (2021) PubMed
5. Sceniak M.P. et al. J. Cell Sci. 132, jcs232892 (2019) PubMed

The submission deadline is Tuesday, September 7, 2021, 5:00 p.m. Eastern Time.

Accessing the Application in proposalCENTRAL:
Prospective applicants must submit an application via proposalCENTRAL (pC). To start an application in pC, users must first log in to their pC account.

If You Need to Create a New Account in pC
To create a new account, go to proposalCENTRAL and click “Need an account?” to start the registration process. Fill in the required fields, check the boxes to agree to pC’s Terms of Service and Acceptable Use Policy and then click “Submit.” For the next steps, see the “If You Have an Existing Account in pC” section below.

If You Have an Existing Account in pC
For all users with a pC account, log in under “Application Login” at proposalCENTRAL and select “Create New Proposal” or click on the “Grant Opportunities” tab. Scroll down to “Simons Foundation” and then click “Apply Now” for the Simons Foundation Autism Research Initiative-Autism Rat Models Consortium in order to start the proposal and access the templates. After all sections are completed, you will be able to click on the “Submit” button.

Application Requirements and Submission Instructions
To submit an application, the following proposalCENTRAL sections must be completed:

1. Title Page: Please provide the following information:
   1. Project title
   2. Indicate the use of Simons Collections biospecimens, data or patient recruitment.
2. Download Templates & Instructions: The following templates are available for download:
   1. 2021 Autism Rat Models Consortium RFA Application Instructions
   2. Simons Foundation Policies and Procedures
   3. 2021 Autism Rat Models Consortium RFA Announcement
   4. Methodological and Statistical Considerations for SFARI Grant Proposals
   5. Induced pluripotent Stem Cell Models of Autism: Experimental Design Considerations
   6. Autism Rat Models RFA Specific Aims Page Template
   7. Autism Rat Models RFA Proposal Narrative Template
   8. Human Participants Study Information Sheet
   9. Chemical and Compound Information Sheet
   10. Biosketch Template
   11. Budget Justification Template
   12. Current and Pending Support Template
   13. Resources and Research Environment Template
   14. Renewable Reagents and Data Sharing Plan Template
   15. Detailed Budget Template for Subcontract
3. Enable Other Users to Access This Proposal: Complete this section to give administrators or collaborators access and to allow other users to submit the application on your behalf.
4. Applicant/PI: The principal investigator (PI) should be listed here. For grants with multiple PIs, the contact PI should be listed here.
5. Organization/Institution: Enter the lead institution. Contact information for the signing official and financial/fiscal officer from your institution is required; select the correct person or enter new names in this section
6. Key Personnel: Indicate key personnel, including but not limited to: principal investigators (not including the contact PI), co-investigators, consultants, postdoctoral research associates and others. In rare circumstances, the applicant organization may designate multiple individuals as PIs who share the authority and responsibility for leading and directing the project, intellectually and logistically. For more information on the responsibilities of PIs, please refer to the relevant questions in the FAQ section.
7. Abstract: Enter the abstract as text in this section.
8. Budget Period Detail: The following information is required for the “Budget Period Detail” section.
   1. Award start date: Proposals selected for funding will be announced in February 2022, and funding will begin on April 1, 2022; May 1, 2022; or June 1, 2022. Please note that grants may not activate without current ethical approval documentation for human participants and/or animal research, unless given prior approval by SFARI staff.
   2. Personnel: Please provide the name, role, appointment type, percent effort, institutional base salary, requested salary, fringe rate and requested fringe for all personnel.
      1. Other considerations: Please note there is no salary cap for PIs or other faculty on a Simons Foundation grant; however, the compensation is prorated according to the individual’s percent effort on the grant. There is no minimum percent effort required for PIs or other personnel on any SFARI award type, but it is expected that the PI will commit sufficient effort to this project to provide a leading intellectual and guiding role on the project. PIs committing less than 15 percent effort to their project should justify their effort level in detail. SFARI funds may be used only for personnel considered employees of the grantee institution who are eligible for benefits. Funds may not be used for stipend or benefit supplementation unless specifically authorized under the terms of the program from which funds are derived. The Simons Foundation reserves the right to modify budgets when an application has been selected for an award (see Simons Foundation policies).
   3. Indirect Costs (IDC): Indirect costs to the primary institution are limited to 20 percent of direct costs with the following exceptions: equipment, tuition and any portion of each subcontract in excess of $25,000. The primary institution may take indirect costs on the first $25,000 modified total direct costs of each subcontract. Indirect costs paid to a subcontractor may not exceed 20 percent of the modified total direct costs paid to the subcontractor.
   4. Equipment: The Simons Foundation will own equipment purchased with foundation grant funds with a unit cost of $50,000 or more. At the end of the grant-funding period or in case of grant termination for any reason, the foundation reserves the right to retain ownership or cede ownership to the PI’s institution. Equipment with a unit cost of $50,000 or less shall be the property of the institution.
   5. Biospecimens: If the proposal includes the use of Simons Collection biospecimens [i.e., from the Simons Simplex Collection (SSC) or Simons Searchlight], the Simons Foundation will review the estimated cost based on the price list on our website. Biospecimen costs will be considered separately from other project costs. Enter the projected figure in the field marked “Simons Collections Biospecimens (No IDC)” in the “Budget Period Detail” section, under “Other Expenses.” A description of use, including the number and type of biospecimens, should be included in the proposal narrative and budget justification (see the “Proposal Attachments” section below). Biospecimen costs must be excluded from the IDC cost calculation.
      1. Please do not use the field marked “For Internal Use Only-Estimated Cost for Simons Collections Biospecimens” below the “Indirect Costs” section in the “Budget Period Detail.”
      2. Investigators interested in recruiting human participants, including those from a Simons Collection must complete and submit a Human Participants Study Information Sheet.
   6. Multiple PIs:
      1. Please note that the applicant PI will be the designated contact PI for the project. The contact PI will be responsible for directing the project and will act as the main point of contact for the foundation by coordinating all administrative deliverables.
      2. Applications with multiple PIs from different institutions who would like to be paid separately must upload in the “Proposal Attachments” section:
         1. Signed signature page for each PI (available for download in the “Proposal Attachments” and “Download Templates & Instructions” sections).
         2. Budget template for each non-applicant PI (available for download in the “Proposal Attachments” and “Download Templates & Instructions” sections).
         3. Direct costs for all non-applicant PIs, which must be given in section 8 (“Budget Period Detail”) in the “Consortium & Contractual Direct” section. Indirect costs for all non-applicant PIs should be included in the “Indirect Costs” section. Please add a separate line for both direct costs and indirect costs for each non-applicant PI.
      3. Applications with multiple PIs from different institutions who will be paid directly by the contact PI’s institution are considered subcontractors. Please refer to the instructions in the “Subcontracts” section below.
      4. Applications with multiple PIs from the same institution do not need to submit additional materials. Additional non-applicant PIs should be listed as key personnel in section 6 (“Key Personnel”) and in section 8 (“Budget Period Detail”), and only one signature page is needed.
      5. Please see the chart below for a detailed breakdown of multiple PI requirements.

   7. Subcontracts:
      1. Applications with subcontracts (including PIs who will be paid directly by the contact PI’s institution) must submit:
         1. Subcontract Detailed Budget (available for download in the “Proposal Attachments” and “Download Templates & Instructions” sections) for each subcontract.
         2. Direct costs for all subcontract PIs, which must be given in section 8 (“Budget Period Detail”) in the “Consortium & Contractual Direct” section. Indirect costs for all subcontract PIs should be included in the “Indirect Costs” section. Please add a separate line for both direct costs and indirect costs for each subcontract PI.
      2. Please see the chart below for a detailed breakdown of subcontract requirements.

Requirements	Multiple PIs (at different institutions that want to be paid separately)	Subcontracts (including subcontract PI)
Signed signature page	Yes	No
Detailed budget template for additional PIs at different institutions	Yes	No
Detailed budget template for subcontracts	No	Yes
Direct costs entered into the “Consortium & Contractual Direct” section of the “Budget Period Detail”	Yes	Yes
Indirect costs entered into the “Indirect” section of the “Budget Period Detail”	Yes	Yes
Key personnel biosketches	Yes	Yes
Key personnel current and pending support	Yes	Yes
Renewable reagents and data-sharing plan	No (contact PI to submit one overall document)	No
Resources research and environment	No (contact PI to submit one overall document)	No
Budget justification	No (a justification should be included in the budget template)	No (a justification should be included in the budget template)

9. Budget Summary: The “Budget Summary” will populate from the saved “Budget Period Detail” section.
10. Organization Assurances: Indicate use of human participants or vertebrate animals in this section and status of approval from the Institutional Review Board or Institutional Animal Care and Use Committee. Grants cannot activate without current human participant and/or animal research ethical approval.
11. Proposal Attachments: The following documents are to be uploaded in the “Proposal Attachments” section, where they are also available for download.
    1. Specific Aims Page: The Specific Aims Page should not exceed one (1) page and should be a summary of the proposed project focused on the research aims of the project, including a concise rationale for the hypothesis, description of preliminary data and experimental approach, and impact on autism research.
    2. Proposal Narrative: The Proposal Narrative should not exceed four (4) pages of single-spaced, size 11 text, 0.5 margins. In the case of multi-PI proposals, applicants may include two (2) additional pages for their Proposal Narratives. For example, an application with two PIs would be allowed six (6) pages single-spaced, size 11 text, 0.5 margins. For an application with three PIs, eight (8) pages single-spaced, size 11 text, 0.5 margins would be allowed for the Proposal Narrative.

       The Proposal Narrative should be considered an expanded version of the Specific Aims Page and used to provide more detail on the following:

       1. Relevant scientific background
       2. Preliminary results when applicable
       3. Specific aims
       4. Experimental design
       5. Pitfalls and alternative strategies
       6. Project significance and relevance to autism
       7. Timeline and milestones

       Figures, figure legends and references should follow the narrative text and will NOT count towards the page limit. References should be in Journal of Neuroscience format, including full author list, title and a link to PubMed. Figures are limited to 10, each fitting on a single page. Please attach them at the end of the three-page narrative in the same PDF file.

    3. Human Participants Study Information Sheet: Required only for investigators proposing to conduct human participant research/clinical studies.
    4. Investigational Compound Information Sheet: Required only for investigators proposing to use chemicals or pharmaceutical compounds in animal research.
    5. Biographical Sketches of Key Personnel
    6. Budget Justification
    7. Budget Templates:
       1. Multiple PIs: Applications with multiple PIs from different institutions that would like to be paid separately must submit a signed budget template for each PI institution.
       2. Subcontract: Applications with subcontracts must submit a budget template.
    8. Progress Report: Investigators currently receiving SFARI funding on science relevant for the current proposal should include a progress report in two (2) pages or less.
    9. Research Environment and Resources
    10. Renewable Reagents and Data-Sharing Plan
    11. Current and Pending Support: Please upload current and pending support for all PIs and key personnel.
    12. 501(c)(3) determination or equivalency letter (foreign institutions only): Please upload, if available, a copy of your U.S. IRS 501(c)(3) determination or equivalency letter as part of the application. (See Simons Foundation policies.)
    13. Signed Signature Page: Applications with multiple PIs from different institutions that would like to be paid separately must submit a signed signature page from each PI institution.
12. PI Data Sheet: Your professional profile will populate this section of the application. If revisions are required, please select “Edit Professional Profile” and go to section 4 (“Personal Data for Applications”). Please note that the contact PI’s ORCID identifier is required. Once the PI’s ORCID iD is provided, you will be able to sync a limited amount of data from your ORCID account with your pC account.
13. Validate: You must click the “Validate” button below to check for any missing required information or files. All missing required information will be listed on the screen. Please correct any missing information before proceeding to the next step.
14. Signature Page(s): The signed signature page is available for download in this section and must be signed by the signing official, then re-uploaded in the “Proposal Attachments” section. Applications with multiple PIs from different institutions that would like to be paid separately must submit a signed signature page for each PI institution.
15. Submit: You will be unable to submit if you have not provided all the required information. Any missing information will be listed on the screen. If your submission is successful, you will receive a confirmation message on the screen and a confirmation email will be sent to the applicant.

Please note that narratives exceeding the appropriate page limit will not be reviewed. Figures (up to 10, fitting on one page each), figure legends and references (formatted in the Journal of Neuroscience style) are not included in the page limit.