General Questions

1. What is the NIH Common Fund?
The NIH Common Fund, managed by the Office of Strategic Coordination in the Office of the Director, supports cross-cutting, trans-NIH programs that require participation by multiple Institutes and Centers. Common Fund programs are intended to be transformative, catalytic, synergistic, cross-cutting, and unique. This program is funded as a short-term, goal-driven strategic investment, with deliverables intended to catalyze research across multiple biomedical research disciplines. More information can be found at https://commonfund.nih.gov/about. 

2. What makes a good application for a Common Fund program? 
Common Fund programs are designed to support actively managed, milestone-driven projects that are different from mainstream studies such as R01 or P01. These projects are expected to work together to address key roadblocks in emerging fields that will transform the way biomedical research is conducted. Reviewers will evaluate whether the project proposes an incremental improvement or a significant advancement which will transform the field. 

3. Why was the NIH Common Fund Cellular Senescence Network (SenNet) program created?
Senescent cells (SC) accumulate with age and have both local and systemic effects.  Removal of SC in adult mice led to significant improvements in both healthspan and lifespan and has spurred interest in some biotech and the pharmaceutical sectors to develop senolytics, drugs that can preferentially eliminate SC. There are, however, several issues that need to be addressed before developing interventions to remove SC in humans. For example, while excessive accumulation of SC as a consequence of aging or in response to cytotoxic therapies is associated with deleterious late-life effects and increased susceptibility to multiple chronic diseases, SC also serve beneficial roles during tissue remodeling in embryogenesis, parturition, and wound healing. In addition, their role as a tumor protection mechanism is also well established.  Thus, understanding what differentiates beneficial from deleterious senescence is a critical knowledge gap. The Cellular Senescence Network (SenNet) program was created to catalyze the development of a framework for mapping cellular senescence and its associated secretory phenotype at high resolution using existing and new tools, to provide comprehensive atlases of cellular senescence in multiple tissues and under diverse conditions, including early development, health, and across the lifespan. In addition, it is expected that SenNet will provide comprehensive sets of biomarkers describing heterogeneous senescent cell states, as well as additional tools to facilitate the study of cellular senescence at the single cell level.

4. What is the goal of SenNet?
The overall goal of SenNet is to catalyze research across multiple biomedical research disciplines by:

• generating multimodal atlases that characterize the heterogeneity and spatial distribution of senescent cells across the lifespan in healthy humans at single cell resolution; 
• determining reliable individual biomarkers or biomarker panels to identify heterogeneous senescent cells as well as their secretory properties in vivo and/or ex vivo;
• establishing the next generation tools, and experimental and computational model systems amenable to perturbations, necessary to construct high resolution atlases of cellular senescence; 
• identifying optimal parameters for regulating senescence, both at the level of inducers and their removal through senolytics, immune therapy, or other interventions;
• dramatically improving imaging tools to identify and validate senescence at the cellular, tissue and whole-body levels. 

5. How is the program structured?
SenNet will scale-up the scope of tissues, technologies, data management, and community engagement that are being addressed during the five-year duration of the program. The program will have two stages: a setup phase in FY2022 and a scale-up phase in FY2023-26.

There are three research initiatives that comprise the program:

• Tissue Mapping Centers (TMCs)

The goal for this set of initiatives, to be issued in FY21, is to generate extensive data from high-content, high-throughput imaging, omics, and other technologies as appropriate, to build, benchmark, standardize, and validate senescent cell maps at high resolution. Tissue Mapping Centers will be expected to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation through data generation, integration, analysis, and interpretation.

• Technology Development and Application (TDA)

These projects will establish proof of principle and validation of the next generation of tools, techniques and methods that can be implemented by the consortium for studying cellular senescence and their Senescence Associated Secretory Phenotype (SASP). Strong priority will be given to technologies to label and visualize senescent cells for fate mapping/lineage tracing and response to perturbations in vivo, and immunotherapy or other senolytic and/or senostatic approaches to eliminate senescent cells. Announcements will be issued in FY21 and FY22

• The Consortium Organization and Data Coordinating Center (CODCC)

This initiative, starting in FY2021, will focus on enhancing, validating, and integrating data from the Tissue Mapping Centers in order to develop and publicize the final maps and atlases describing senescent cells in healthy humans and, at a later stage, mice. The CODCC will serve as an organizational hub for the consortium, and it will collect, store, curate, and disseminate all data, metadata, analyses and visualization tools, computational models, and completed tissue maps generated by the SenNet consortium. It will develop controlled access workspaces for consortium working groups, and an outfacing portal, the Senescence Atlas, to the scientific community for access to the tools, technologies, and tissue-level maps and atlases developed by the TMC and Technology Hubs.

The goal is to accommodate increasing data volume and evolving data types; and it is expected that SenNet will leverage the resources of existing single-cell atlas programs such as HTAN, HCA and HuBMAP; and have the capability to support both human and murine datasets.

6. What is expected to happen during the first phase of the program?
During the first year of the program, the Consortium will establish working groups, policies, SOPs, joint activities, and the infrastructure to support these activities. Individual projects will be expected to recruit staff, carry out calibration and benchmarking experiments, and build collaborations with other Consortium members as well as other national and international tissue mapping initiatives.

During years 2-5 of the program, the Consortium will develop maps and eventually atlases of cellular senescence in multiple tissues obtained from healthy humans. As the projects mature, the CODCC will develop and populate a data matrix using data generated from validated assays, and both the TMC and CODCC will promote the development of joint projects such as cross-validation studies or integrated analysis. Individual projects will be expected to generate validation and pilot data by the end of the 5-year cycle.

During years 2-5, the Consortium will be expected to have regular data releases of publication-quality data, to work with the wider research community to establish data and resource sharing policies, as well as creating tools and engaging in activities that will accelerate awareness and re-use of Consortium data. Individual projects will validate and implement emerging technologies into their data generation pipelines, regularly contribute significant amounts of well annotated, high-quality data to the CODCC in standardized formats, and analyze the generated data for new insights into inter-individual variability.

7. Will there be a similar atlas of cellular senescence in mice? 
The current plan is to develop an atlas of cellular senescence in murine models too, but specific plans for this effort are still in the developing phase. The human atlas is expected to be more complex and thus take longer time to develop, and this is the reason this first effort is dedicated to the human atlases.  

8. Why are the human and mouse projects being released at different times?
The NIH expects that the murine effort might take a shorter time to reach its goal compared to the human atlas effort. 

9. What do you mean by Phase 1? What is Phase 2?
Phase 1 of all Common Fund projects typically last 5 years and that is the scope of effort in the current RFA and discussed here. If this 5-year phase is successful and worthwhile to continue, and depending on the availability of funds, the project might be extended for up to a maximum of additional 5 years, which would, if approved, constitute Phase 2. 

10. What is the relationship between SenNet and other similar programs?
The ultimate goal of the Cellular Senescence Network (SenNet) is to catalyze the development of a framework for mapping cellular senescence and its associated secretory phenotype at high resolution and to provide atlases of cellular senescence in multiple tissues, in response to multiple inducers and modifiers, and under diverse conditions, including early development, and across the lifespan. This effort builds upon and extends existing single cell tissue mapping programs including the Human Tumor Atlas Network, Human Biomolecular Atlas Program, and Human Cell Atlas. Together with the SenNet program, these efforts will continue to generate important resources for the scientific community that will inform future research and, ultimately, clinical decision-making.

11. What is the Common Fund Data Ecosystem (CFDE)?
The Common Fund Data Ecosystem (CFDE) is intended to provide the infrastructure needed to help solve key challenges facing Common Fund Data Coordinating Centers. CFDE will include a portal or central access point for Common Fund data sets, tools, and other digital objects, through which users can access and compute on data in a cloud environment. This CFDE portal is not designed as a data repository or platform but will instead link multiple data platforms that have been established through Common Fund programs and create cloud workspaces for users to access and compute on data across the different platforms. While users may continue to access an individual data set via the platform created for that data set, the CFDE will foster new discoveries and support different types of analyses by enabling queries of multiple data sets simultaneously. The CFDE will provide user support through automated help tools, online courses, webinars, and in-person training events. By providing infrastructure, advice, resources, best practices, common components, and services to fit the needs of Common Fund programs, the CFDE will increase the utility of Common Fund digital objects by making them more findable, accessible, interoperable, and reusable, also known as FAIR. The CFDE will require a collaborative effort, involving Common Fund Data Coordinating Centers who represent the data generators for each program, and a central coordinating component known as the CFDE Coordinating Center (CFDE-CC). The NIH Common Fund (CF) supported programs are intended to provide resources that accelerate discovery across many different biomedical research fields. These resources include large data sets and associated digital tools needed to mine and analyze the data. To maximize their impact, data sets and tools generated by the CF programs must be usable together. Towards achieving this goal, the CF created the Common Fund Data Ecosystem (CFDE), a data management infrastructure where the interconnected ecosystem facilitates scientific advances by making CF data and digital objects usable and useful both within a program and in combination with data from other programs.

The SenNet Program will be structured to facilitate engagement in the CFDE. This will be achieved by designing the program components that: i) use the cloud platforms for data storage and management for easy access to data, ii) construct a data infrastructure which follows FAIR principles for usage of the data, and iii) adapt the appropriate data and metadata standards to enable interoperability of the generated data with other data sets, and iv) adapt visualization tools for accessing data with various end-users in mind.

For more information, please visit https://commonfund.nih.gov/dataecosystem/faqs

12. What is the Science and Technology Research Infrastructure for Discovery, Experimentation, and Sustainability (STRIDES) Initiative?
As the scale of data-related research grows, NIH continues to explore opportunities to support NIH researchers’ use of the cloud for data storage and compute. The STRIDES Initiative enables NIH and NIH-funded investigators to more easily take advantage of cloud services. The STRIDES Initiative has negotiated agreements with commercial cloud service providers (CSPs) for 1) discounted rates on cloud services, 2) access to professional services to provide support on how use the cloud effectively, 3) access to training to help learn more about the cloud and its capabilities, and 4) the potential for collaborative engagements to explore topics of special interest to NIH.

For more information, please visit, https://commonfund.nih.gov/dataecosystem/faqs

13. Where can I find more information about SenNet?
Announcements and regular updates will be posted on the program website: https://commonfund.nih.gov/senescence

14. Who should I contact with questions?
General inquiries can be sent to CS2@nih.gov. For questions about individual RFAs, Science/Research, as well as Grants Management, contacts are indicated in each announcement and these individuals should be your first contact for questions related to that RFA. In addition, the Common Fund SenNet program is administered via a team of NIH program experts.

Science-Related Questions

15. What do you mean by “tissue”, “organ”, and “organ system”?
Tissue is any aggregate of cells that have similar structure and function. An organ is typically a self-contained component of the body that has a specific vital function; an organ is composed of a collection of tissues. An organ system is a group of organs that act together to perform a bodily function.

16. What do you mean by “healthy” human tissue?
In this context, it is recognized that ‘absolute’ health is not well defined, and the focus is on analysis of tissues that are healthy for the life stage being analyzed. The focus is on human donors without major chronic conditions known to significantly impact the morphology, function or biomolecular profile of the tissue to be analyzed. 

17. Will SenNet fund projects that do not use “healthy” human tissue?
The focus of the program is on understanding the intrinsic intra-, inter-, and extra- cellular biomolecular distribution of senescent cells and their secretory molecules in healthy human tissue. The program will focus on producing maps and atlases from fresh, fixed, or frozen healthy human tissue using in situ and dissociative techniques that have high-spatial resolution. On the other hand, unhealthy mammalian tissues may be used to reduce experimental variability while establishing feasibility, or to establish protocols. However, the end product of each TMC and the Consortium as a whole must be on healthy human tissue.

18. What are major considerations for choosing which tissues to analyze?
Tissue Mapping Centers are strongly encouraged to choose tissues in which they have appropriate expertise and access to high quality materials. It should be noted that in making funding decisions, NIH staff will consider tissue coverage across the Consortium, with preference given to applications that cover tissues not covered by other applicants. Applicants should plan a prospective collection strategy, including collection of a full health history, as well as appropriate epidemiological, socioeconomic and anatomical data alongside data on specimen collection. Tissue Mapping Centers are strongly encouraged to identify robust biological and statistical rationales for sampling decisions from human donors, for example whether to focus on intra-individual sampling, inter-individual sampling or temporal sampling across the lifespan. The TMCs will implement accepted best practices for collection and preservation of tissues, adapting them as needed for Network-wide use. Tissue Mapping Centers are strongly encouraged to develop enrollment criteria that will minimize the risk of abnormal or degraded tissue and pursue broad donor consent for unrestricted sharing of data for research purposes to maximize the utility of biospecimens and data.

19. What is the difference between a tissue map and an atlas?
For SenNet, a tissue map is a high-resolution representation of the quantitative distribution of intrinsic biomolecules found in senescent cells present in human tissue. These biomolecules fall into many classes including but not limited to DNA, RNA, proteins, lipids, and metabolites. A biomolecular atlas is a collection of related biomolecular maps. Applicants are strongly encouraged to propose assays that can be easily multiplexed to produce comprehensive maps of the distribution of multiple classes of biomolecules associated with cellular senescence across a tissue, including both intracellular and extracellular compartments. For this, development of high-quality validated biomarkers will be crucial.

Tissue Mapping Centers are responsible for generating the individual maps for the tissues under study. The CODCC is responsible for integrating these maps together, and providing a framework for generating atlases of functional, structural, and biomolecular data on cellular senescence that enable studies of inter-individual variability, changes across the lifespan, and across the health-disease continuum.

20. What tissue or organs are within the scope of the program? 
There are no preferences or limitations to the tissues that will be analyzed as part of SenNet, beyond each project being expected to work with non-diseased human tissue. Given (1) technology limitations, (2) availability of high-quality tissue, and (3) tools, data, and analysis available from similar programs, applicants are strongly encouraged to consider: (1) how their choice of tissues provides a unique and synergistic opportunity for SenNet, (2) the rationale and synergy between the technologies, tissues and analysis of tissues and organs proposed, and (3) the significance of the biological insights that will be gained from the data generated and analyzed. Additional details can be found in each RFA. Projects that propose studying non-human, diseased or dysfunctional tissues are not within the scope of the program. Motile human cells in the context of a tissue, such as tissue resident macrophages, are within the scope of the program.

21. What tools and technologies are within the scope of the program?
The Technology Development and Application (TDA) FOA seeks to establish the next generation of tools, techniques and methods that will be foundational for mapping senescent cells in the human body at single cell resolution. Successful projects will develop, demonstrate and validate technologies that can generate extensive biomolecular data about senescent cells and their context in multiple human tissues to comprehensively identify them. Applications are expected to be high impact with a milestone-driven engineering approach that considers design, testing and evaluation, and to bring together multi-disciplinary teams that will result in technologies that can be easily disseminated to other laboratories. SenNet supports the development and application of high-content, high-throughput, cost-effective assays that generate high-quality quantitative and reproducible data for characterizing cells and the extracellular structures at high-resolution. Technologies that only assay a small number of biomolecules, have low sensitivity or specificity, are not generally applicable to most tissues or require significant optimization for each tissue, do not provide a reproducible quantitative readout, are not capable of high-throughput analysis, do not have high-resolution, do not identify specific biomolecules, or are not cost-effective will be considered as low priority. Tools and technologies which require significant pre-processing of the tissue that results in significant biomolecular degradation will also be considered low priority.

FOAs encourages technologies that can address, but are not limited to, the following challenges:

• Modification of existing microfluidic methods (e.g., Drop-seq) to capture rare and large senescent cells, which are often discarded in these assays
• Mapping RNA and protein expression of more than one hundred biomolecules of interest, that will be determined by the consortium, across whole organs at a single cell resolution for the purpose of functionally identifying senescent cells
• Developing robust, comprehensive and unbiased descriptors of senescent cell types and states present in a tissue, including different cell types such as tissue-resident immune cells and pluripotent cells
• Studying both intracellular and extracellular biomolecular features (e.g., Senescence Associated Secretory Phenotype, SASP) within tissues to help understand cellular communication and contextual function
• Advancing methods for understanding the degree of organizational variability in senescent cells in the same tissue between different individuals and multiple tissues from the same individual
• Developing methodologies to affect and deliver an intervention to specific senescent cell types or tissue types; Optimizing techniques that can robustly identify cell lineage, differential allelic expression, niche environments, viral infection or other microenvironment-defining biomolecular patterns in tissues

22. What is meant by “high-resolution”, “high-content”, and “high-throughput”?
For SenNet, a high-resolution assay is one that can reliably and reproducibly assign detected biomolecules to individual cells or extracellular compartments of a tissue. This dimension is typically understood to be at a length scale of around one micron, though projects may propose techniques within an order of magnitude depending on the biomolecules and tissues being studied. A high-content approach is one that maximizes identification of tissue features through a combination of biomolecular depth, spatial resolution, and multiplexing of complementary, multi-parameter assays. A high-throughput pipeline is one that maximizes the bandwidth of data production to result in any or all of the following: 1) accelerated speed of analysis, so that hundreds or thousands of samples can be analyzed at once, 2) greater depth of analysis, so that hundreds or thousands of molecules can be analyzed in a single sample, or 3) enhanced capacity for volume, so that a given set of molecules can be analyzed in all the cells within a larger tissue sample. Approaches that minimize the volume of tissue that will be analyzed while maintaining cellular resolution and high-biomolecular content are strongly encouraged.

23. What will be considered unresponsive?
The focus of SenNet is on characterizing cellular senescence in healthy human tissues. As such, the following types of applications will be considered as non-responsive and will not be reviewed:

• Projects exclusively focused on mechanistic studies aimed at understanding biological processes, but that will not result in the generation of a comprehensive map and atlas
• Projects proposing maps and atlases constructed using solely non-human samples or human biospecimens with diseased or dysfunctional characteristics
• Projects proposing maps and atlases based upon a single experimental assay (i.e., a map or atlas constructed from a single data type)

24. Will SenNet fund projects using dissociative techniques?
Yes, projects addressing cellular senescence within the context of their tissue, and cells isolated from defined tissues will be considered as responsive. Usage of either (or both) approaches should be well-justified for the technologies to be used and the outcomes sought (e.g., dissociated cells might be more appropriate for biomarker development, while undisturbed tissue might be more appropriate for studies of tissue distribution within an organ.) In addition, projects can use dissociative techniques in combination with complementary imaging approaches or propose dissociation assays where the spatial organization of the tissue can be inferred, and the conditions varied to analyze intracellular and extracellular regions. In all cases, however, investigators are strongly encouraged to use multiple assays that can be cross validated, to minimize perturbation and degradation of tissue during pre-analytical process, and to optimize and standardize their assays.

Funding and Review Related Questions

25. Does SenNet use the NIH grant mechanism?
SenNet will use cooperative agreements for all 3 initiatives. A Cooperative Agreement is a support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific and program staff will assist, guide, coordinate, or participate in project activities. A cooperative agreement funding mechanism supports discrete, specified, circumscribed projects to be performed by investigators in an area representing their specific interest and competencies. Cooperative Agreement projects are typically driven and directed through clearly defined, quantitative milestones that are negotiated between NIH and the applicants at the time of award. In addition to a Program Officer from the administering institute, each award will be assigned to a Project Scientist(s) from NIH who will participate with the Principal Investigators on a Steering Committee. NIH staff will not direct the research but will assist in aligning progress with the goals of the program and promote interaction with other members of the Consortium. There are several key expectations described in each RFA such as:

• Attendance at Consortium meetings, workshops, and conference calls
• All investigators are under a confidential disclosure agreement regarding all private information within the Consortium
• Participation in cross-validation of their own and others’ tools/technologies

26. Is funding based on a payline? 
No. In addition to the scores provided by reviewers based on scientific merit, funding decisions will also consider programmatic needs, as defined in the funding announcement, and the availability of funds.

27. Who is eligible to apply for funding?
Academic organizations, small businesses, large businesses, non-profit organizations, eligible agencies of the Federal Government (e.g., NIH intramural program), and Foreign institutions are eligible to apply as described in the “Eligible Applicants” or “Eligibility” section of each announcement.

28. My organization is an XYZ or I am an ABC investigator. Does that mean I have any special preference or disadvantage?
All applications will be assessed solely based on the evaluation criteria described in the funding announcements. We encourage applications from nearly any organization (domestic or foreign), to see the “Eligible Applicants” or “Eligibility” section of the relevant announcement. NIH policies such as Continuous Submission or New Investigator status do not apply to RFAs. There is no preference or disadvantage for organizations beyond the review criteria listed in the relevant announcement.

29. Can work be performed outside the United States?
Applications from foreign entities as PI are only acceptable for RFA-RM-21-009 (TDA). However, foreign applicants can be included as collaborators in RFA-RM-21-008 (TMC) and RFA-RM-21-010 (CODCC). 

30. Is there a recommended period of performance and budget level?
Period of performance and budget should be driven by scope and scientific need. Budgets and timelines are expected to vary from project to project. In the case of RFA-RM-21-008 (TMC) and RFA-RM-21-010 (CODCC), a maximum time of 5 years can be requested, while for RFA-RM-21-009 (TDA), total duration of the projects is 4 years, with an expected 50/50 distribution between the UG3 and UH3 phases.

31. Can an institution/research team submit more than one application to any one RFA or submit related applications to different RFAs? 
For each specific RFA there is no limit on the number of applications an institution or team may submit, provided the applications are scientifically distinct.  However, an investigator designated as the Contact PD/PI or MPI of an application under any of the Sen Net FOAs must not be the designated Contact PD/PI or MPI of another application under a companion SenNet FOA.   

32. Can research teams span institutions? 
Yes. Team members may span multiple institutions, as it is possible that the full range of expertise needed for a proposal may not exist at one institution. Teams are expected to assemble the expertise across labs, disciplines, and institutions as needed to achieve the goals of the project and the SenNet.

33. How will SenNet applications be reviewed? 
Applications will be reviewed by a Special Emphasis Panel (SEP) or panels assembled by Center of Scientific Review (CSR). Standard and FOA-specific review criteria as described in each FOA will be considered in the review process.

SenNet Consortium Questions

34. What is the SenNet Consortium?
The SenNet Consortium will be made up of SenNet awardees, NIH staff, External Program Consultants, and other scientists and groups that the Steering Committee agrees to include within the Consortium (as associate or affiliate members). 

The goal of the SenNet consortium is to identify and functionally characterize the heterogeneity of senescent cells across multiple tissues in human health, and lifespan at single-cell resolution. Through collaborative efforts, the consortium will generate a multimodal, multidimensional Atlas of senescent cells in various human tissues; develop innovative tools and technologies to identify and characterize senescent cells; and aggregate data across the Network into a searchable Atlas of Cellular Senescence. The Consortium will also ensure the utility of the database and promote collaboration through Network engagement with the research community.

35. What is the SenNet Steering Committee?
The  SenNet Steering Committee (SC) is the self-governing body for the  SenNet Consortium. The roles of the SC are to recommend direction for the SenNet Consortium that are consistent with the program goals, develop Consortium policies and projects to build synergy and improve communication and collaboration between the projects, and to provide a forum for discussing progress, challenges and opportunities for the Consortium. 

The Steering Committee will be composed of one representative (contact PD/PI or other senior level investigator) from each SenNet grant (Tissue Mapping Centers, Technology Development Projects, and the SenNet CODCC) for the duration of the respective project, who will have one vote each.

NIH program staff members will participate in SenNet Steering Committee meetings as non-voting members, but Steering Committee decisions will be subject to final review and approval by the NIH. 

If needed, other government staff members may also participate in SenNet Steering Committee meetings as non-voting members. 

At the first meeting of the Steering Committee following award issuance, 2-3PD(s)/PI(s), representing different SenNet awards, will be selected to serve as chairpersons of the Steering Committee. All SenNet Steering Committee decisions and recommendations that require voting will be based on a majority vote. 

The SenNet Steering Committee will meet monthly by videoconference and in-person at the SenNet semi-annual Steering Committee Meeting, or as needed.

The SenNet Steering Committee will:

• Identify scientific and policy issues that need to be, or can benefit by being, addressed at the Network level and develop recommendations to NIH Program Officials for addressing such issues. 
• Review progress of the SenNet toward meeting the overall Network goals. Ensure that all SenNet members utilize the resources developed by the SenNet CODCC, TMCs and Technology Development Projects. 
• Coordinate dissemination of Network output to the broader senescence research community.
• Ensure that the Network takes advantage of existing NIH resources and programs.
• Establish, as necessary, subcommittees to ensure progress of the individual Centers and the Network.

36. Who are the External Program Consultants?
As part of the SenNet program, NIH staff will engage approximately 5-8 external program consultants (EPCs) not funded as part of the program but with relevant scientific and consortium experience to provide input and advice to the NIH WG. This guidance could include reviewing and evaluating the progress of the entire SenNet Program or individual awardees as well as recommending changes in priorities for the SenNet Program based on scientific advances within and outside of the Consortium. The EPCs are senior, scientific experts and end users who are not directly involved in the activities of the SenNet Program, engaged on an as-needed basis to advise on specific issues and who agree to a confidentiality policy.  NIH is solely responsible for appointing EPCs for variable durations of service. EPCs are invited to participate in the semi-annual consortium-wide grantees meeting as well as SC and WG meetings as needed. A subset of EPCs may also meet by phone or web at other times of the year, as needed. Annually, the EPCs will provide individual assessments to the NIH on the progress of the Consortium and will present individual expert recommendations regarding any changes in the SenNet Program as necessary. The assessments and recommendations will be provided through the NIH WG to the Director of the Office of Strategic Coordination.

37. What role does the NIH have in the SenNet Consortium?
NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in grants, providing technical assistance, advice and coordination. NIH staff will participate as non-voting members in the Steering and other committees and will be responsible to select External Program Consultants. The roles of NIH are described in further detail in each Funding Opportunity Announcement.

38. What are the expectations for investigators participating in the Consortium?
In addition to carry out the specific research proposed in their individual applications, investigators funded as part of the program will be expected to participate in a variety of Consortium activities, agree to its policies and implement agreements. The Consortium will have a range of regular teleconferences, including Steering Committee and Working Group calls. In addition, investigators will be expected to attend the Annual Investigator Meeting in-person and other appropriate face-to-face meetings and workshops organized by the Consortium and should budget accordingly. Funded projects will be expected to participate in Consortium projects, that may include development of SOPs and metadata standards, cross-site validation studies using the same tissue specimens, joint analysis projects, multi-site training programs, or coordinated outreach initiatives.  Applicants are strongly encouraged to propose and budget for these activities as part of their applications. In addition, the Consortium will establish a range of policies and expectations, including the use of pre-print servers for rapid dissemination of results, regular data submissions, and publication of experimental protocols. A more complete list of Consortium policies are in development at this time.

Award-Related Questions

39. What are the plans for data and resource sharing for this program?
NIH intends that the products of the SenNet be broadly available to the research community to establish the foundations for a map of cellular senescence abundance and characteristics in the healthy human body that other programs and the international community can build upon, including methods, tools, reagents, biospecimens, datasets, and software. 

A primary goal of the SenNet is to lay the foundation for a widely accessible atlas of cellular senescence and this will require data and resources to be shared quickly and openly once validated. Restrictive licensing and sharing practices for SenNet-generated data, tools, and resources could substantially diminish their value and public benefit. All funded investigators must facilitate the public release and dissemination of results, data, reagents, technologies, and other products generated through their SenNet awards in a timely manner and abide by Consortium and NIH policies. 

Accordingly, awardees should manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would prevent or block access to or use of SenNet data, tools, and resources for research purposes will be considered as hindering the goals of the SenNet.

The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees, through the CODCC, will develop such policies, methods, and standards in concert with the NIH.  These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing. Applicants should provide a detailed resource and data sharing plan with milestones and timeline in the application. Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

40. Will there be potential collaborations within the program?
Yes - it is expected that the SenNet investigators will form partnerships and collaborations both within and outside the Consortium. However, these collaborative projects are expected to form in year 2 and beyond. 

41. Can NIH provide additional guidance on including milestones in the application?
All projects will be milestone-driven with clear go/no-go criteria that are quantifiable and milestones must be included in the application. Prior to funding an application, the Program Official will contact the applicant to discuss the proposed milestones and any changes suggested by NIH staff or the NIH review panel. The Program Official and the applicant will negotiate and agree on a final set of approved milestones which will be specified in the Notice of Award. These milestones will be the basis for judging successful completion of the work and will be reviewed annually.

Milestones are not specific aims or broadly aspirational statements of what a project is expected to achieve. Instead, milestones are intermediate steps towards the completion of concrete goals and must include clear and quantitative criteria for success. A milestone can be a defined event, achievement, or important stage that is used to indicate the progress of a project.  

42. Can changes be made to the Research Plan during the project period?
Since this is an actively managed program, investigators should expect that their goals and budgets will be modified during the project period. Changes to the Research Plan of any given project must be discussed and pre-approved by the Steering Committee, and should be in line with, and serve the overall goal of the SenNet. If Research Plans are modified, NIH might withhold funds in any given year and release the funds only when the modified Consortium activities have been approved. To promote synergy and collaboration between projects in the Consortium, NIH staff may also work with awardees to amend and refine goals and milestones. As tools and techniques are developed within the Consortium and other programs, investigators may also be asked to cross-validate these approaches. Investigators can also propose minor changes to the research approach as needed during the course of the project.

43. Can SenNet select only certain portions of an application to fund?
Yes. NIH staff may choose to fund a portion of an application based on reviewer feedback. This option may result in a reduction in project budget and/or project period. Projects may also be funded as pilot projects with a reduced budget and duration, with funds being restored for later years if the work is of high programmatic priority and milestones have been met or exceeded.

RFA Specific Questions

RFA RM-21-008 (Tissue Mapping Centers, TMC): 

44. Are there preferred tissues or approaches?
NIH expects to fund at least one Center focused in each of the following areas: 1) analysis of multiple discrete, complex organs from the same individual or a region of the body composed of multiple tissues, 2) analysis of a complete organ or system and 3) analysis of dynamic changes in senescent cells as a function of age, developmental stage or other relevant variables. 

Higher programmatic priority will be given to: 1) applications that propose to study complete human organs not being proposed by other TMCs, 2) that propose a synergistic and well-validated set of assays for multiscale and multi-modal analysis and 3) that have existing informed consent from a diverse range of donors or their families for explicit sharing of clinical and genomic data.

TMC applicants are strongly encouraged to: 1) optimize or adapt appropriate existing tissue collection protocols, assays, and analytical methods, 2) plan a prospective tissue collection strategy, including collecting appropriate clinical data, 3) develop enrollment criteria and acquisition strategies that will minimize the risk of abnormal or degraded tissue as part of a quality management strategy, 4) pursue explicit consent from the donor or their family for unrestricted sharing of data for research purposes, 5) incorporate, optimize and validate emerging assays that will generate complementary quantitative, high-content, high-throughput biomolecular data, 6) to reuse and adapt existing and widely-used data and metadata standards, ontologies, schemas, and formats, and to use common data elements, machine readable formats, structured reports and to minimize manual data entry where possible, 8) use existing software packages and analysis methods, such as R-based or Python-based solutions, and 9) contact NIH Staff to discuss the alignment of their proposed work with the goals of this FOA and the SenNet Program.

RFA RM-21-009 (Technology Development and Application (TDA):

45. What tissues can projects propose as part of a TDA application?
The goal of the TDA initiative is to accelerate the development of the next generation of tissue analysis tools. While the SenNet program is interested in the whole body, TDA projects are encouraged to: 1) choose a practical mammalian tissue during the UG3 phase that best exemplifies the capabilities of their technology, and 2) to propose a range of human tissues that shows the generalized nature of the technology and its potential for scale-up and future incorporation into the Tissue Mapping Centers during the UH3 phase. Projects may choose to acquire their own tissue or may consider working with one of the Tissue Mapping Centers to access human tissue biospecimens. For projects funded during the UH3 phase, there will be an expectation that grantees from this FOA will participate in cross-validation studies with other Consortium projects and to submit significant high-quality data on human tissues to the CODCC. TDA applicants are encouraged to use existing data and metadata standards where possible and to develop a plan and roadmap for data handling, including a timeline with milestones for generating different tiers of data including feasibility, validation and publication quality data, and how they will work with the CODCC to successfully submit publication-quality data to the CODCC during the UH3 phase.

46. What technologies are appropriate for a TDA application?
Projects that develop the next generation of tools, techniques and methods to allow analysis of cellular senescence or the SASP at single cell resolution, or that significantly improve existing technologies in this domain are given priority. In contrast, applications that propose technologies that cannot be scaled for comprehensive analysis of multiple human tissues or that cannot be multiplexed with other assays will not be given priority.

RFA RM-21-010 (Consortium Organization and Data Coordination Center (CODCC):

47. Who is responsible for building the final Cellular Senescence Atlas? 
The TMCs are responsible for, among other things, generating individual multidimensional maps into tissue-level atlases proposed by that TMC. The CODCC is responsible for, among other things, integrating these individual tumor atlases together into a searchable Atlas resource of functional, structural and biomolecular data that will enable comparative studies across tissues.