Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The National Cancer Institute (NCI) will fund a new Cancer Systems Biology Consortium (CSBC) through multiple Funding Opportunity Announcements (FOAs) to promote systems biology approaches to cancer research. The CSBC network will consist of U54 CSBC Research Centers (RFA-CA-15-014), relevant, specialized U01 research projects (currently supported under PAR-13-184), and one Coordinating Center (to be supported by this FOA). Concurrently, NCI sponsors the Physical Sciences in Oncology Network (PS-ON), a collection of U54 Research Centers (PS-OC, PAR-14-169) and U01 specialized Research Projects (PS-OP, PAR-15-021) that focus on integrating physical science approaches with cancer biology and oncology to address important questions in cancer research.

CSBC and PS-ON investigators provide distinct and complementary skill sets for addressing basic and translational cancer research problems. Therefore, this FOA aims to create a common coordinating body to facilitate resource sharing, collaborations, and outreach activities across the two networks. The CSBC/PS-ON Coordinating Center will contribute to the research missions of the CSBC and PS-ON by establishing (1) the Resource Coordinating Hub, (2) the Collaboration and Pilot Project Hub, and (3) the Outreach Hub. In carrying out its roles, the CSBC/PS-ON Coordinating Center is expected to work collaboratively with CSBC and PS-ON investigators, other investigators collaborating with the CSBC and PS-ON, and NCI program staff.

Cancer is a complex disease system involving multiple molecular, genetic and cellular events.

From its early initiation through progression and metastasis, cancer can adapt and evolve as a result of both internal and external cues. The emergence of resistance to therapy and targeted drugs is a direct consequence of the adaptive and heterogeneous nature of a tumor. These properties make cancer difficult to predict, prevent and/or treat. There has been significant progress in characterizing the genetics of cancer, as well as the downstream effects on the molecular and cellular pathways that are critical for the initiation and progression of cancer. These single parameter studies have highlighted the need to understand cancers as integrated systems of genes, networks, and intercellular interactions.

Cancer systems biology attempts to develop predictive computational models that integrate the multivariate perturbations with the dynamic changes associated with cancer. High-throughput technologies, such as genomic sequencing, transcriptomics, metabolomics, proteomics and high-content imaging, have generated enormous amounts of descriptive data. Systems analyses and predictive modeling are necessary to integrate across these disparate datasets to derive an understanding of the cancer process. The resulting models and computational tools are diverse and not always easily available for dissemination and use, due in part to the lack of a unified repository or forum for the wider cancer systems biology community. Additionally, mathematical and computational biology modeling is often reduced to snapshot glimpses illustrating a narrow use of the technology to facilitate publication and proof-of-concept demonstration. Such limited usage of elegant techniques and tools represents a major roadblock to the field of cancer systems biology.

Similarly, systematic physical characterization of tumor cells and their microenvironment across temporal and spatial scales has and will continue to generate a significant amount of phenotypic data. For example, the PS-ON recently released a compendium of physical data describing commonly utilized cancer cell lines. Wide access to the datasets generated by PS-ON funded investigators is necessary for efficient mechanistic discovery and translation to clinically useful insight.

Centralized infrastructure that provides access to, and facilitates widespread usage of, the broad range of data sets, mathematical models, and computational tools developed by the CSBC and PS-ON is an urgent unmet need. With the establishment of the CSBC/PS-ON Coordinating Center, the CSBC and PS-ON are in a unique position to provide leadership by example through development of a Resource Coordinating Hub. Applicants are encouraged to read RFA-CA-15-014 , PAR-13-184, PAR-14-169 and PAR-15-021 for more information regarding the research performed by CSBC and PS-ON U54 Research Centers and U01 Research Projects. For information about data, software, and models generated by the former NCI-supported Integrative Cancer Biology Program (ICBP), applicants are encouraged to visit the ICBP Resource website. For information about current PS-ON data and models, applicants are encouraged to visit the PS-ON website.

Collaborations among biomedical scientists, bioengineers, mathematicians, and computational biologists are fundamental for the CSBC research goals focused on systems-level analyses. The Integrative Cancer Biology Program (ICBP), a former NCI-funded initiative linked with a currently active collaborative U01 Specialized Research Project component (PAR-13-184), developed a community of cancer systems biologists with disparate, but complementary, expertise. Similarly, the PS-ON includes a cohort of physical scientists, who in conjunction with cancer biologists/physician scientists, are employing physical science methods and theories to tackle cancer research questions. Previous trans-ICBP or trans-PS-ON research collaborations were initiated through scientific meetings, research exchanges, and pilot projects funded through the respective U54 Research Centers. As both programs contain aspects of physical, mathematical, and engineering approaches to cancer biology, there exist opportunities for cross-program collaboration.

Applicants for the CSBC/PS-ON Coordinating Center need to have sufficiently broad scientific expertise and capabilities in the field of cancer systems biology and relevant aspects of bioinformatics that would allow them to play a leadership role in ensuring that the consortium-wide scientific objectives will be met.

The CSBC/PS-ON Coordinating Center will provide leadership, infrastructure, and administration for three activities that are expected to enhance the integration of the CSBC and PS-ON:

The Resource Coordinating Hub

Note: In the context of this FOA the term "resources" relates to data, models, computational tools, etc. generated by CSBC and PS-ON research and, potentially, by other related NCI-supported programs.

The Resource Coordinating Hub will be an online source for CSBC and PS-ON researchers (and others) to locate and download digitally identifiable, curated data, models, and computational tools created by the CSBC and PS-ON. The type of resources deposited in the Resource Coordinating Hub will be dependent on the research goals and output of each CSBC and PS-ON U54 Research Center and U01 Research Project, requiring the CSBC/PS-ON Coordinating Center to be responsive and flexible in its ability to integrate, present, and share novel data and modeling techniques.

The Resource Coordinating Hub will serve as a central destination with online tools that users can employ to locate and access data, models, and computational tools with accompanying documentation describing the resource. Importantly, it is expected that the CSBC/PS-ON Coordinating Center will have the capability to curate data, models, and computational tools ensuring that resources deposited in the Hub are functional for the community. (Note: In the context of this FOA the term "curation" is defined as the verification of functionality of a resource and refers specifically to the application of mathematical models and/or computational tools given a specific data set (most likely the data utilized in publication with the resource).) Due to the wide range of data types, modeling and computational techniques employed by the CSBC and PS-ON, the Resource Coordinating Hub is not expected to be a one-size-fits-all infrastructure that facilitates data analysis, model construction, or tool execution spanning all methods utilized by each network.

Note: Because of the overlapping timing of the funding of various CSBC and PS-ON research parts (including the CSBC U54 Research Centers), the detailed scope of research that the Coordinating Center will have to handle remains to be determined. Therefore, the CSBC/PS-ON Coordinating Center needs to have broad expertise and flexible capabilities in a wide range of experimental and modelling approaches relevant to cancer research. For information about data, software, and models generated by the former NCI-supported Integrative Cancer Biology Program (ICBP), applicants are encouraged to visit the ICBP Resource website. For information about current PS-ON data and models, applicants are encouraged to visit the PS-ON website.

Collaboration and Pilot Project Hub

The primary goal of the Collaboration and Pilot Project Hub is to facilitate trans-consortium research collaborations (intra-CSBC or between CSBC and PS-ON or other NIH supported programs) through the initiation and organization of scientific interaction across experts in the fields of systems biology and cancer research. This goal covers organizing the CSBC and PS-ON annual Investigator meetings, as well as a broad (and open) range of options for other possible activities and formats to promote scientific interactions for investigators at all levels (e.g., periodic workshops, focus or working groups, in-person and internet-mediated interactions, , etc.)

A second major responsibility of the Collaboration and Pilot Project Hub will be the management of the restricted CSBC Pilot Project Fund. This responsibility includes solicitation of project proposals from CSBC investigators, organization of their review by CSBC investigators and the NCI program staff, and administration of funds after approval by the CSBC Steering Committee. Note: trans-PS-ON pilot projects are supported by an independent fund as detailed in PAR-14-169 and PAR-15-021. Responsibility for coordinating the trans-PS-ON projects is not included under this FOA.

Outreach Hub

The goal of the Outreach Hub is to coordinate promulgation of research advances, concepts, and capabilities of the CSBC and PS-ON to cancer researchers as well as broader scientific communities. Each CSBC and PS-ON U54 Research Center is expected to build a vibrant and active Outreach Core. It is expected that the Outreach Hub, in collaboration with NCI program staff, will help to integrate and expand the outreach activities of the U54 Research Centers to promote the CSBC and PS-ON as resources for the broader research community and the public.

The CSBC program, that includes the Coordinating Center, will be governed by CSBC Steering Committee (see Section VI.2. Administrative Agreement Terms and Conditions of the Award. )

As the efficiency of the funded research is an important priority for NCI, CSBC awardees will be required to participate in an external evaluation process of the CSBC program coordinated by NCI Program Staff.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

The CSBC/PS-ON Coordinating Center PD/PI (contact PD/PI for applications with multiple PD(s)/PI(s)) must be a scientist with strong expertise in cancer systems biology, computational biology, or mathematical modeling techniques.

If so desired, PD(s)/PI(s) on applications for CSBC or PS-ON Research Centers or Projects (under RFA-CA-15-014, PAR-14-169, PAR-15-021) may also serve as PDs/PIs on applications for the CSBC/PS-ON Coordinating Center award under this FOA.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Dan Gallahan, Ph.D.
Division of Cancer Biology (DCB)
National Cancer Institute (NCI)
Telephone: 240-276-6180
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Under Budget Justification, provide the budget break down to indicate the direct costs expected for the Resource Coordinating Hub, Collaboration and Pilot Project Hub, and Outreach Hub. The maximum total direct costs per year is $750,000. In planning the costs, the applicants are expected to follow the scheme of sub-limits over individual years of the project period as indicated below:

• Resource Coordinating Hub:
  • Year 1: at least $500,000
  • Year 2: at least $400,000
  • Years 3-5: up to $300,000
• Collaboration and Pilot Project Hub
  • Funds should be allocated to support collaboration-promoting activities proposed in Sub-section C: Collaboration and Pilot Project Hub. Applicants must budget for organization of the CSBC/PS-ON Annual Investigator Meeting, including such costs as meeting venue, meeting materials, and travel for the U24 PD(s)/PI(s). Note: do NOT include any travel costs for other CSBC or PS-ON investigators (Travel costs of these investigators to Annual Investigator Meeting will be covered by their respective awards)..
  • Some funds will be restricted via the Terms and Conditions of the award to support post-award trans-network pilot projects involving CSBC awardees as recommended by the CSBC Steering Committee and approved by NCI. The awarded CSBC/PS-ON Coordinating Center will manage this restricted fund as described in this FOA. These funds should be presented in the Other Direct Costs category under the heading "CSBC Pilot Project Fund" in the following amounts: Year 1: $0M, Year 2: $100,000, Years 3-5: at least $300,000.
• Outreach Hub: $150,000 each year

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: Specific Aims should address the development of the three required functional units referred to as "hubs" (Resource Coordinating Hub, Collaboration and Pilot Project Hub, and Outreach Hub) as described in Section I of the FOA under the Scope and Objectives.

Research Strategy: In lieu of the Standard sub-sections listed in the SF424 (R&R) Application Guide, the Research Strategy must consist of the following modified sub-sections.

Sub-section A: Overview and Significance

Provide an overview of the Coordinating Center vision by stating how the Coordinating Center hub structure will enhance and facilitate CSBC and PS-ON research. Specific aspects of the hub that lead to potential synergy among members with respect to advances in cancer systems biology and physical oncology should be especially highlighted. Applicants are encouraged to describe how their organizational structure and concepts will utilize the experience of individual team members, especially with regards to breadth of knowledge of cancer systems biology and physical science techniques. State how, if applicable, existing or novel support from organizations outside the scope of this FOA (i.e. industry, foundations) might contribute to build each hub. Applicants are encouraged to propose and justify any other coordination activity that would be useful to the CSBC and PS-ON, but is not listed explicitly elsewhere in the FOA.

Sub-section B: Resource Coordinating Hub

Note: In the context of this FOA the term "resource" relates to data, models, computational tools, etc. generated by CSBC and PS-ON research and, potentially, by other related NCI-supported programs.

Describe a plan for creation and maintenance of the Resource Coordinating Hub that addresses, at a minimum, all the aspects, attributes, and functions of the Hub:

• A readily accessible website for CSBC and PS-ON members and the public that provides information about the CSBC and PS-ON initiatives and serves as an interface for the Resource Coordinating Hub.
• Hosting requirements of the Resource Coordinating Hub, including estimates for data storage and a plan for the infrastructure required to host large multi-scale datasets. Data deposited to the Resource Coordinating Hub should be hosted on the NCI-supported web resource NCIP Hub. It is not a requirement of this FOA to host mathematical models or computational tools on NCIP Hub.
  • Applicants are encouraged to read RFA-CA-15-014 , PAR-13-184, PAR-14-169 and PAR-15-021 for more information regarding the research performed by CSBC and PS-ON U54 Research Centers and U01 Research Projects. For information about data, software, and models generated by the former NCI-supported Integrative Cancer Biology Program (ICBP), applicants are encouraged to visit the ICBP Resource website. For information about current PS-ON data and models, applicants are encouraged to visit the PS-ON website.
  • Include a plan for handling secure data. User registration may be required for tracking purposes and to access restricted data.
• Documentation, submission, and resource storage practices for the Resource Coordinating Hub should be detailed with a plan for timely implementation of a system that integrates viewpoints from CSBC and PS-ON members.
• Resource tracking through the use of digital identifiers.
• Data and model curation that provides the community with confidence that resources deposited in the Resource Coordinating Hub are employable by members of the CSBC and PS-ON. Note: In the context of this FOA the term "curation" is defined as the verification of functionality of a deposited resource and refers specifically to the application of mathematical models and/or computational tools given a specific data set (most likely the data utilized in publication with the resource). The applicants should present plans to curate resources submitted to the Resource Coordinating Hub and subsequent delineation of these resources as such.
• Resource migration from existing and legacy repositories specifically serving the PS-ON and the former ICBP (see the PS-ON website and the ICBP Resource website for examples of currently hosted resources).
• The hub should contain an easy-to-query, extensive information resource about the different systems biology and physical oncology research approaches and data utilized by the CSBC and PS-ON.
• End user support for the Hub, including online user documentation, and support for the CSBC and PS-ON communities in their data deposit, curation, and usage activities.

In addition, applicants should address the following specific items:

• Highlight any innovative aspects that the applicant believes will strengthen the elements of the Resource Coordinating Hub and enhance its flexibility and ease-of-use by the CSBC, PS-ON, and the scientific community.
• Provide an example workflow that would illustrate how CSBC and PS-ON resources (e.g., raw and processed data and data sets, bioinformatics tools, mathematical models etc.) will be entered into the Resource Coordinating Hub and displayed to the end user. This includes identification, procurement, and deposition of data from CSBC and PS-ON investigators.
• Describe how ideas and concerns of CSBC and PS-ON awardees regarding Hub employment will be addressed, including how those ideas and concerns might be integrated into the current application.
• Provide a framework for evaluating performance of the Resource Coordinating Hub, including benchmarks and a timeline for achieving full functionality.

Sub-section C: Collaboration and Pilot Project Hub

Note: It is expected that collaboration-related activities will involve the CSBC, PS-ON and, potentially, other NCI- or NIH-supported programs. However, funds from the CSBC Pilot Project Fund will be awarded only to CSBC investigator-led projects. Information about PS-ON trans-network pilot project funding can be found in PAR-14-169 and their coordination will not be the responsibility of the CSBC/PS-ON Coordinating Center.

• Collaboration-related Activities. Describe specific plans for activities that may lead to and/or facilitate collaborations among CSBC investigators (e.g., between those at CSBC Research Centers and those conducting U01 Projects), between the CSBC and PS-ON, or between the CSBC/PS-ON and other organizations. State any innovative aspects and how they go beyond normal team-building activities.

In addition to the required Annual Investigator Meetings, for a range of other collaboration-related activities might be appropriate. Examples of potential appropriate activities include, but are not limited to:

• Specialized in-person meetings that focus on a particular research area of interest across the CSBC, PS-ON and the wider cancer research community.
• Monthly video conferences that highlight newly published research from PS-ON or CSBC-associated scientists at all levels.
• Workshops or working groups that focus on trans-consortium model building or tool sharing with the goal of developing PS-ON or CSBC-funded pilot projects.
• Specialized meetings that highlight collaboration opportunities within the CSBC, PS-ON or across NIH Institutes and sponsored programs.
• Think tanks that assess the evolving needs of physical scientists, cancer systems biology experimentalists, mathematicians, computer scientists and computational biologists, with the goal of developing trans-consortium collaborations or pilot projects to address recommendations.
• Specialized scientific retreats to facilitate early-stage multidisciplinary investigator interaction and data presentation/discussion (including both the CSBC and the PS-ON investigators).
• Mechanisms to enrich research experiences of graduate students and/or post-doctoral fellows, e.g., through research-based exchanges (trans-CSBC or CSBC-PS-ON).
• Trans-Consortium/Network Pilot Project-related Activities. Describe plans for the Hub to facilitate and logistically support pilot projects utilizing the restricted CSBC Pilot Project Fund. These projects should be initiated and directed by CSBC members but may involve non-CSBC collaborators. Provide a plan for pilot project solicitation and scientific review (which could be by other CSBC Investigators with the involvement of NCI Program Staff members and/or external experts, if appropriate). Include details of how solicitation topics will be decided and how priorities will be set. It is expected that final selection of projects will be made by the CSBC Steering Committee (with approval for funds release by NCI program staff).

Sub-section D: Outreach Hub

Describe how the Outreach Hub will promote the advances of cancer systems biology and physical oncology research to the scientific and wider communities. At a minimum the Outreach Hub will publish a periodic newsletter to inform the scientific community about scientific advances in the CSBC and PS-ON. Applicants should propose other activities that might be appropriate for the Outreach Hub. Examples include, but are not limited to:

• Development of a summer program to expose scientists, engineers and mathematicians at all levels to cancer systems biology and physical oncology-based research.
• Community or crowd-sourced systems biology competitions or challenges that engage members of the CSBC, PS-ON and the public.
• Dissemination of CSBC and PS-ON activities and accomplishments through social media outlets. This aspect might include construction of a website targeting non-scientists to educate the public about the contribution of systems biology and physical oncology to cancer research.

Letters of Support:

In addition to standard items, the following specific letters of support are required.

• Letter(s) of support from senior administration officials or other institutional officials from the PD(s)/PI(s) institution(s) must be provided demonstrating a commitment to the proposed center's stability during the lifetime of the award.
• A letter(s) stating the ability of the PD(s)/PI(s) institution(s) to provide administrative support (through its Office of Sponsored Research or equivalent) for multiple sub-contractual agreements expected for the authorized uses of the Collaboration and Pilot Project fund.
• Additional letters of support from any resources outside the scope of this FOA (e.g., industrial or foundational partners) utilized in the application, if applicable.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• This terms and details of this plan are expected to be consistent with the proposed activities of the Resource Coordinating Hub.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Important Update: See NOT-OD-16-006 for updated review language for applications for due dates on or after January 25, 2016.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this FOA, note the following:

Because of the overlapping timing of the funding of various CSBC and PS-ON research parts (including the CSBC U54 Research Centers), the Coordinating Center must be able to accommodate a variable and broad scope of research and related needs. Therefore, the CSBC/PS-ON Coordinating Center needs to have relatively broad and flexible expertise and capabilities in a wide range of experimental and modelling approaches relevant to cancer systems biology and physical oncology.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the proposed Center address the needs of the research [consortium] that it will [serve]? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research [consortium]?

Specific to this FOA: Will the CSBC/PS-ON Coordinating Center activities facilitate or expedite CSBC and PS-ON research that would otherwise be delayed or infeasible?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing [systems biology and/or physical oncology] research? Do the investigators demonstrate significant experience with coordinating collaborative [basic] research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their [organizational plans] appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this FOA: Does the CSBC/PS-ON Coordinating Center leadership team have the appropriate breadth and balance of expertise in systems biology and related areas? How strong are the investigators' background and leadership experience in building/maintaining online resources for the scientific community? Are the PD(s)/PI(s) and key investigators likely to be able to accomplish their objectives in a highly collaborative, fair, and flexible manner?

Innovation

Does the application propose novel [organizational concepts] in coordinating the research [consortium] the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of [organizational concepts] proposed?

Specific to this FOA: Does the applicant propose innovative approaches to resource sharing and collaboration that are likely to be adopted as an overall philosophy of the CSBC and PS-ON U54 Research Centers and U01 projects involved? How likely is it that the innovative solutions proposed by the applicant will endure beyond the funding period?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research [consortium] the Center will serve? Are potential problems, alternative strategies, and benchmarks for success presented? If the Center is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the [consortium]? Are an appropriate plan for work-flow and a well-established timeline proposed?

Specific to this FOA: Are the three main research objectives for the Coordinating Center (resource sharing, collaboration, and outreach) sufficiently addressed and properly balanced? Is the approach of the Resource Coordinating Hub comprehensive and likely to succeed given the disparate approaches and research output of the CSBC and PS-ON? How sufficient are the approaches to promote trans-consortium cooperation and collaboration and plans for logistic support of these activities? Are the plans for the Outreach Hub well-conceived and realistic in terms of the potential to raise community-wide awareness of cancer systems biology and physical oncology research and outcomes?

Environment

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research [consortium] it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Specific to this FOA: Is the computational infrastructure adequate to meet the needs of the project? How well does the environment promote collaborations and transdisciplinary approaches to solving the technical and scientific goals of the CSBC/PS-ON Coordinating Center? If applicable, do the optional resources proposed by the applicant that are outside the scope of this FOA (eg., foundation or industry partners) result in value-added capability for the CSBC and PS-ON?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Cancer Institute, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The PD(s)/PI(s) assume responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research and administration supported by the U24 award. Specific responsibilities include:

• Inclusion, as appropriate, of all resources and investigators from CSBC and PS-ON U54 Research Centers (RFA-CA-15-014 and PAR-14-169) and U01 specialized research projects (FOA to be released in 2016, PAR-13-184 and PAR-15-021) in activities coordinated by the U24 Coordinating Center.
• Ensuring that the tools developed within the Resource Coordinating Hub under this FOA are freely available to all CSBC and PS-ON members.
• Committing and maintaining throughout the life of the award a minimum of 2.4 person-months of effort per year to the Coordinating Center investigator designated as the PD/PI. For applications with multiple PD(s)/PI(s), a minimum of 1.2 person-months of effort per year is required.
• Implementing procedures to solicit input and feedback from the CSBC and PS-ON community and integrating those ideas into the three coordinating center hubs.
• Seeking opportunities for collaboration with NCI and NIH networks, consortia, and research resources. For example, the NCI Center for Biomedical Informatics & Information Technology. These activities may be facilitated by NCI program staff.
• Agreeing to be an active participant in the CSBC and PS-ON, including attending the Annual Investigators Meetings, participating in other consortium sponsored meetings and workshops, and participating in collaborative activities.
• The CSBC/PS-ON Coordinating Center PD/PI (contact PD/PI for applications with multiple PD(s)/PI(s)) will be required to serve as an ex officio member of the both the CSBC and PS-ON Steering Committees. In this non-voting role, the CSBC/PS-ON Coordinating Center PD/PI will be required to attend meetings, but is not under obligation to abide by Steering Committee decisions.
• Solicitation of applications from CSBC investigators for pilot projects to be supported by the CSBC Pilot Project Fund and organization of the scientific review of these applications.
• Overseeing the distribution and administration of Collaboration and Pilot Project Hub funds through appropriate sub-contractual arrangements with awarded institutions.
• Reporting progress to the NCI Program Officials on all CSBC/PS-ON Coordinating Center research and outreach activities annually. The PD(s)/PI(s) may be expected to provide additional information, outside the scope of the standard reporting requirement, as needed and requested by program staff on a semi-annual basis.
• Participating in monthly teleconferences with NCI Program Staff to coordinate efforts and provide updates on Coordinating Center activities.
• Maintaining a transparent and fair organizational structure for CSBC and PS-ON participants.
• Awardee will retain custody of and have primary rights to the data and software developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

One or more designated NCI Program staff members will have substantial involvement as Project Scientists in the awards under this FOA. The specific roles of the substantially involved NCI staff members include the following activities:

• Serving as voting members on the CSBC Steering Committee and the PS-ON Steering Committee.
• Assisting both Steering Committees, the CSBC/PS-ON Coordinating Center awardees, and individual U54 and U01 awardees of both CSBC and PS-ON programs in identifying potential areas of interaction and collaboration.
• Facilitating collaborative research efforts that involve multiple CSBC Research Centers and/or CSBC Research Projects and would be suitable for consideration by the Collaboration and Pilot Project Hub of the U24 Coordinating Center award.
• Assisting the awardees as a resource in facilitating their broader interactions with other NCI and NIH programs to disseminate results, tools, and models from the CSBC and PS-ON and take advantage of existing NIH/NCI resources and infrastructures.
• Monitoring the operations of the CSBC/PS-ON Coordinating Center and making recommendations on overall project directions and allocations of CSBC Center funds.
• Ensuring that the Resource Coordinating Hub, to be developed by CSBC/PS-ON Coordinating Center, is provided to CSBC and PS-ON members in a reasonable and expeditious way.
• Evaluating the effectiveness and facilitating consortium-wide adoption of Resource Coordinating Hub practices.
• Reviewing the progress of the CSBC/PS-ON Coordinating Center, conducting periodic site visits, and taking other actions as needed.
• Participating in organizing annual meetings, specialized workshops, and webinars of the CSBC and PS-ON consortia.
• Additionally, an agency program official or IC program director will be responsible for the standard scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

A. The Steering Committee for CSBC. This Steering Committee will be a governing body for CSBC and will include as voting members representatives of the CSBC awardees and NCI Program staff members as follows:

• The contact PD/PI (for CSBC Research Centers with multiple PD(s)/PI(s)) from each awarded CSBC Research Center.
• A maximum of six PD(s)/PI(s) (for U01 Projects with multiple PD(s)/PI(s)) from the awarded CSBC U01 projects. Representatives from U01 projects will be rotated every 18-24 months to allow all U01 contact PD(s)/PI(s) to serve on the Steering Committee. A PD/PI can vote only once if they have contact PD/PI status on two CSBC grants.
• NCI Project Scientist(s), maximum 2

All voting members of the Steering Committee will have one vote. Additional NIH/NCI program staff and other government staff may participate in CSBC Steering Committee meetings as non-voting members. The structure is designed to allow awarded investigators and NCI staff to work together to facilitate trans-CSBC activities based on synergistic expertise and projects.

Two PD(s)/PI(s), representing two different CSBC awards, will be selected to serve as chairs of the Steering Committee starting at the first meeting of the Steering Committee following award issuance. All CSBC Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The contact PD/PI of the awarded CSBC/PS-ON Coordinating Center (U24) will be a permanent non-voting member.

The Steering Committee may have additional non-voting members.

The CSBC Steering Committee will meet annually at the CSBC Annual Investigator Meeting and as needed.

The CSBC Steering Committee will:

• Identify scientific and policy issues that need to be, or can benefit by being, addressed at the Consortium level and develop recommendations to NIH/NCI Program Officials for addressing such issues.
• Review progress of the CSBC toward meeting the overall Consortium goals.
• Ensure that all CSBC members utilize the CSB Hub developed by the U24 CSBC/PS-ON Coordinating Center.
• Approve and prioritize the funding of the collaborative pilot projects administered by the U24 CSBC/PS-ON Coordinating Center utilizing the restricted Pilot Project Fund.
• Coordinate dissemination of Consortium output to the broader cancer research community.
• Review the potential of Shared Resource Core(s) at individual Research Centers to serve the needs of other Research Centers or Research Projects and develop appropriate policies for such activities as appropriate and consistent with achieving the goals of the program.
• Ensure that the Consortium takes advantage of existing NCI and NIH resources and programs.
• Establish, as necessary, subcommittees to ensure progress of the individual Centers, Projects, and the Consortium.

B. PS-ON Steering Committee. This already formed Steering Committee is a governing body for PS-ON and includes as voting members representatives of the PS-ON awardees and NCI Program staff members.

The contact PD/PI of the CSBC and PS-ON Coordinating Center (U24) will be added as a permanent non-voting member of this Steering Committee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Dan Gallahan, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6180
Email: [email protected]

NCI Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.