Q: Why was this program established?

A: Single cell analysis has recently emerged as an important field of research because technologies have improved in sensitivity and throughput sufficiently to begin measuring and understanding heterogeneity in complex biological systems and correlating it with changes in biological function and disease processes. By profiling individual cells it is possible to resolve rare cells, transient cell states, and the influence of organization and environment on such cells and states, which cannot be described by ensemble measurements. The long-term goal of the SCAP is to accelerate this move towards personalizing health to the cellular level by understanding the link between cell heterogeneity, tissue function and emergence of disease through the discovery, development and translation of innovative approaches which will dramatically change the way cells are characterized.
The SCAP will focus on supporting work which will systematically measure, analyze and model cell-to-cell variation, and identify crucial differences and rare biological states, which may have important functional consequences. To robustly and systematically describe cell level heterogeneity, projects are expected to take a multiplexed approach with minimal perturbation, which can be applied reproducibly to any complex tissue. Technologies and methods must also be capable of capturing spatiotemporal information to understand the organization, evolution and response of cell states as part of a functional population. In addition, the SCAP emphasizes the application of these technologies to in situ populations of cells from multicellular organisms to link cell state measurements with complex, functional tissues which can inform our understanding of disease processes.

Q: What distinguishes this Common Fund Program from other Funding Opportunities?

A: This Program is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. Common Fund initiatives address key roadblocks in biomedical research that impede basic scientific discovery and its translation into improved human health. In addition, these programs capitalize on emerging opportunities to catalyze the rate of progress across multiple biomedical fields.

Q: Which Funding Opportunities (FOAs) are part of this Program?

A: The SCAP has been designed as a five-year program with several components: (1) the collection, analysis and sharing of comprehensive expression datasets to understand the role of heterogeneity in tissues and systemically and identify critical parameters and states; (2) the discovery of new, innovative tools for spatiotemporal imaging, manipulation, analysis and modeling of a biologically relevant population of cells with minimal perturbation; (3) milestone-driven validation and translation of technologies for characterizing single cells in situ meeting the needs of end-users; and (4) development and coordination of a multidisciplinary research community through workshops and other collective endeavors. Further details can be found on the Program’s website (http://commonfund.nih.gov/singlecell/).

Currently there are three FOAs:

• Studies to evaluate cellular heterogeneity using transcriptional profiling of single cells (U01)
• Exceptionally Innovative Tools and Technologies for Single Cell Analysis (R21)
• Accelerating the Integration and Translation of Technologies to Characterize Biological Processes at the Single Cell Level (R01)

Additional initiatives will be announced contingent upon NIH appropriations.

Q: In two sentences, what distinguishes the RFAs?

• RFA-RM-11-013 – Studies to evaluate cellular heterogeneity using transcriptional profiling of single cells (U01) - Applicants must propose the transcriptomic analysis of human cells in order to improve our understanding of “noise” and the functional significance of heterogeneity. The awards will be in the form of cooperative agreements which will involve substantial NIH staff involvement to build synergy between the funded projects
• RFA-RM-11-014 – Exceptionally Innovative Tools and Technologies for Single Cell Analysis (R21) - The focus is on establishing proof of concept tools which will potentially transform the field of single cell research by verifying their feasibility in situ. These cross-cutting, high-impact projects do not need preliminary data but must clearly be capable of overcoming key roadblocks in our understanding of heterogeneity.
• RFA-RM-11-015 – Accelerating the Integration and Translation of Technologies to Characterize Biological Processes at the Single Cell Level (R01) - The focus is on accelerating the translation of technologies which have been demonstrated in principle with preliminary data to offer significant advantages to clinical and biomedical researchers. Validation of the technology must be established using animal or human cells and be part of a set of milestones towards establishing the technology as a robust well-characterized tool.

Q: Can someone at NIH let me know whether my idea is a good fit for this Program? Should I submit a Letter of Intent?

A: Investigators are strongly encouraged to email the Scientific Contact listed in individual FOAs to check whether their ideas are responsive to the goals of the initiative. Investigators are also strongly encouraged to submit Letters of Intent as detailed in the FOAs to assist with programmatic and review planning. General questions related to the program should be directed to the co-coordinators of this program via email to: [email protected]

Q: How is the Program administered?

A: Awards will be administered by NIH Institute and Center staff on behalf of the NIH Office of the Director.

Q: What is meant by “cross-cutting”?

A: For these RFAs, cross-cutting means that an approach or technology can be applied in multiple scenarios to improve understanding of multiple diseases or conditions. The SCAP is designed to cut across the missions of multiple NIH Institutes of Centers and to support projects which will have trans-NIH impact and unlikely to be funded by any single entity.

Q: What does “in situ analysis” mean?

A: For these RFAs, in situ analysis means the analysis of individual cells in the context of a complex, multicellular environment that preserves the original structural and functional characteristics of the native environment. This includes in vivo analysis in whole organisms or a defined tissue of interest, ex vivo analysis of intact tissues or of bodily fluids, or highly specialized preparations that replicate the three-dimensional architecture of a complex tissues. For studies supported by these RFAs “in situ analysis” excludes studies of clonal cell lines, single cell organisms and dispersed cell culture preparations. Analytical methods employed should minimize perturbation of cells prior to measurement as well as strive to maintain overall tissue function before and during measurement.

Q: What does multi-parameter / multiplexed analysis mean?

A: The goal for these RFAs is to support the development of tools and approaches which will transform how cells are characterized. To uniquely and reproducibly characterize cell states within a heterogeneous population, a sufficiently large parameter space needs to be used covering more than one type of quantitative measurement. The endpoints may include physical characteristics, biochemical concentrations, molecular analysis and subcellular organization, however to be cross-cutting and transformative, it would be of interest to capture multiple readouts of cell state from single cells in tissue. In addition, the novel measures should offer significant improvement in sensitivity and/or specificity over current capabilities. For example a study looking at mechanical perturbation of single cells using two or three optical probes or a patch clamp study of the electrophysiology of single cells would not be responsive to these RFAs.

Q: What is meant by “first-in-class” tools? If something is truly first-in-class, how can it be compared against existing technologies?

A: For these RFAs, first-in-class approaches or tools are those that are a fundamental departure in concept or design from those currently employed, particularly those that resolve a previously intractable barrier to single cell analysis. While it is understood that these are intrinsically difficult to compare against existing technologies, a “nearest neighbor” technology can be chosen for comparative purposes.

Q: Are milestones the same as specific aims?

A: No. While specific aims are usually focused on a particular scientific question or even a proposal to make a tool or database, milestones are very concrete indicators of progress at critical junctures of the study. Thus, an aim can contain several milestones, or a late milestone can integrate and encompass more than one aim. In the context of tool development, they can be important steps in assembling or feasibility testing of components, up to and including a final proof-of-principle or validation test. In the context of data acquisition, they can be critical steps in the optimization of equipment, staff placement, collaborative logistics, or thresholds of data acquired, analyzed or banked. While the aims describe the expectation of an outcome, the milestones describe how you will know whether progress has been achieved.

Q: What is a resource sharing plan?

A: A resource sharing plan is required for all FOAs in this program and it is expected that this plan will describe in sufficient detail how research resources created by the project will be managed, consistent with NIH policies and guidance, please see: http://grants.nih.gov/grants/sharing.htm. This plan should include information on the management of intellectual property, clinical, raw and processed data, model organisms, details of an repositories being used, and software. More detailed and specific information is in given Section IV 2 of each FOA.

Q: Are Investigators required to dedicate a minimum number of calendar months?

A: Yes. Given the technical requirements and coordination that will be required, Principal Investigators are expected to dedicate at least 2.4 calendar months of effort for projects submitted in response to RFA-RM-11-013 and 3 calendar months for projects submitted in response to RFA-RM-11-015.

Q: Are individuals at all stages of their careers eligible?

A: Yes, individuals at all career stages are eligible to apply. However, applicants must be able to show evidence for their claim of innovativeness and potential to conduct ground-breaking independent research and have authorization from their institution to apply. Women, members of groups underrepresented in biomedical or behavioral research and multidisciplinary teams are especially encouraged to apply.

Q: Are foreign scientists and institutions eligible?

A: Yes. However, applications from foreign institutions must comply with all NIH policies concerning grants to foreign (non-U.S.) organizations. Please see: http://grants.nih.gov/grants/policy/nihgps_2013/nihgps_ch16.htm#_Toc271265275

Q: Are individuals employed by government agencies, non-academic, or for-profit organizations eligible?

A: Individuals from all organizations that can otherwise apply to the NIH for funding and that are willing to abide by the terms and conditions that NIH requires are eligible for this program. Please see the specific Funding Opportunity Announcements for further details.

Q: How do applications differ from investigator-initiated applications?

A: Investigators are encouraged to carefully read the Funding Opportunity Announcement for each initiative, in particular Section IV which describes application and submission information. For all applications, investigators are expected to clearly articulate the public health relevance of their work and the size and nature of the communities which will be impacted. In addition, to build synergy amongst funded projects and accelerate the field in general, investigators are expected to describe a detailed resource sharing plan. The review criteria noted in the FOAs are also tailored to each initiative.

Q: What post-award requirements must I fulfill?

A: All projects funded by this program are expected to set-aside travel funds for investigators to travel to the annual workshop. You will be required to submit an annual report as per standard NIH reporting requirements (Non-Competing Continuation Grant Progress Report (PHS 2590)) and financial statements as required in the NIH Grants Policy Statement. In addition, specific FOAs may require details such as a minimum percentage effort from the PD/PI, as described in the FOA. Furthermore, to help the NIH evaluate this program, you may be contacted periodically to report on your latest research efforts.

Q: What makes a good application for a Common Fund Program?

A: Common Fund Programs are meant to support projects that are different from mainstream studies by addressing key roadblocks in emerging fields that will transform the way biomedical research is conducted. Applicants must explicitly address how the proposed research will have an impact which cuts across the interests of individual NIH Institutes and Centers and the reviewers will evaluate whether the project proposes an incremental improvement or a significant advancement which will transform the field. Applicants must also provide compelling justification for Common Fund support rather than from an individual NIH Institute or Center.

Q: Can I submit a similar project to two funding opportunities at the same time?

A: The general policy of the Public Health Service, which includes the NIH, does not allow multiple submissions of essentially the same proposal to any of its components. 

Q: What must be done before I submit an application to Grants.gov? 

A: It is important that you check immediately with your sponsored research office to determine whether your institution is registered with Grants.gov. Please note that the registration process could take up to two weeks. The institution’s Authorized Organizational Representative (AOR) is responsible for completing the registration process. If your institution is not already registered, it must first register with the Central Contractor Registry (the Credential Provider) and then with Grants.gov at http://www.grants.gov/web/grants/register.html. Both the institution and the applicant must also complete a one-time registration in the NIH eRA Commons in order to submit applications to NIH. Institutional officials are responsible for registering investigators in the eRA Commons. You should work with your AOR (also known as Signing Official in the eRA Commons) to determine your own institution’s process for registration.

Q: Where can I find help registering for Grants.gov? 

A: For help with the Grants.gov registration process, contact Grants.gov customer support at 1-800-518-4726 (Toll Free), Monday–Friday, 7:00 a.m. to 9:00 p.m. (Eastern Standard Time), or at [email protected].

Q: Where can I find help in submitting my application to Grants.gov? 

A: For help with the technical aspects of submitting an application to Grants.gov, check the resources available at Grants.gov. If you need assistance, contract Grants.gov customer support at 1-800-518-4726 (Toll Free), Monday through Friday, 7:00 a.m.–9:00 p.m. (Eastern Standard Time), or at [email protected].

Q: Where can I find help in registering for the eRA Commons? 

A: Step-by-step directions for registering with eRA Commons are available at http://commons.era.nih.gov/commons/registration/registrationInstruction….
For questions regarding the Commons registration process, contact the NIH eRA Commons help desk at phone: 301-402-7469 or 866-504-9552 (Toll Free); 301- 451-5939 (TTY) business hours Monday–Friday, 7:00 a.m.–8:00 p.m. (Eastern Standard Time).

Q: How will applications be reviewed?

A: Applications will be reviewed by NIH staff for completeness and then by a multi-disciplinary group of scientific experts convened by the Center for Scientific Review (CSR) in accordance with NIH peer review procedures and using review criteria outlined in the FOA. Significance, innovation and potential to transform the field of single cell analysis will be the primary determinants of scientific merit. The review panels will also be looking for convincing evidence that the project can address the key roadblocks identified and can be catalytic for further research though NIH Institute or Center-funded mechanisms. It is extremely important to keep this review process in mind when describing your project plan; minimize jargon and use language that scientists in other fields can understand and read the specific review criteria listed in the Funding Opportunity Announcement.

Q: When will my application be reviewed, and by whom?

A: Questions about review should be directed to the Scientific Review Officer (SRO) assigned to the application.

Q: Will I have an opportunity to submit an update before my application is reviewed?

A: Limited materials can be submitted post submission as described in NOT-OD-10-115: http://grants.nih.gov/grants/guide/url_redirect.htm?id=11148

Q: How will awards be selected for funding?

A: The NIH Director will make the final selection of awards based on review recommendations and programmatic considerations.

Q: If my application is not funded, will I have an opportunity to revise and resubmit? 

A: No. However, there may be an opportunity to submit a new application to a future Single Cell Analysis initiative, or you may be able to incorporate some elements of your proposal into an application through a different FOA.

Q: Can the decision of the review panel be appealed?

A: No. There is no appeal process.

MANAGEMENT OF COOPERATIVE AGREEMENTS FOR RFA-RM-11-013

Q: Are there specific requirements for Cooperative Agreements?

A: Yes. Cooperative Agreements are grants where NIH Project Scientists play a collaborative role with the funded research teams. Applicants are strongly encouraged to read the full FOA, especially Section VI, Award Administration Information for details on the roles and responsibilities of the PI and the NIH.

Q: Will the funded groups be expected to meet and collaborate?

A: Yes. The U01 awardees will meet regularly via teleconference and in person to provide regular updates and discuss technical challenges. In addition, groups will be expected to share resources and analytical tools to promote validation. Applicants should budget for travel to one annual in-person meeting that will likely coincide with the Single Cell Analysis Program annual workshop.

Q: Given that this Funding Opportunity uses the U01 mechanism, will technical assistance be available for interested applicants?

A: Yes. A technical assistance phone conference will be held for potential applicants on December 7, 2011 from 11:30-12:30 EST. NIH staff will be available to answer questions related to this FOA. Please contact Andrea Beckel-Mitchener ([email protected]) for information on how to access to this conference. For applicants not available at this time, notes from the teleconference will be available on the Common Fund Single Cell Program website (Single Cell Analysis​) within a few days following the call.