NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 (supported under this FOA), specialized U01 research projects (currently supported under PAR-13-184), and a Coordinating Center (supported under RFA-CA-15-015).

Integrating around a team of multi-disciplined investigators, the CSBC Research Centers are expected to utilize the tools of systems biology to develop a comprehensive research program in cancer biology. Employment of novel computational tools and mathematical models should result in new mechanistic insights and hypotheses that are beyond the scope of normal intuition. Equally important is the validation or testing of the models in an appropriate biological setting. The CSBC initiative is intended to further the field of cancer systems biology.

As part of the CSBC, the CSBC Research Centers are expected to play an active role within the cancer research community by providing intellectual leadership, scientific resources, and outreach activities. Investigators from both the U54 Research Centers and U01 Projects will be expected to collaborate and share resources and expertise across the Consortium and participate in Consortium activities and annual meetings. This intra-CSBC collaboration will be coordinated and managed by NCI staff and the U24 Coordinating Center. This Coordinating Center will also play a role in the integration of CSBC scientific findings with those of complementary programs, notably the Physical Sciences in Oncology Network (PS-ON). Therefore, this unit is referred to as "CSBC/PS-ON Coordinating Center".

The aim of the CSBC is to develop a systems approach to cancer research to complement and expand our current understanding of cancer across many physical- and time-scales, with the ultimate goal of improving cancer prevention, detection, diagnosis, prognosis, and therapy. 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. 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. However, these single parameter studies have also highlighted the need to understand cancers as integrated systems of genes, networks, and intercellular interactions.

Most cancers result from the dysregulation of multiple pathways that govern various aspects of cell biology. 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.

Cancer systems biology is uniquely poised to address fundamental questions in cancer research. Among the pressing questions in cancer that are particularly amenable to a systems approach are: interpreting the impact of multiple genetic changes on phenotype, tumor dynamics and evolution, tumor heterogeneity, tumor progression and metastasis; tumor-stroma or tumor-immune system interactions; understanding epigenetic and other non-mutational influences on cancer classification/diagnosis; predicting drug sensitivity and resistance to inform clinical trial design. Continued development and application of systems engineering and computational methodologies will be needed to address these questions, including the development of new mathematical and computational methodologies, multi-scale modeling approaches that are capable of integrating across scales from the molecular to the population and robust, publicly available, datasets (e.g. genomic, transcriptomic, proteomic, phosphoproteomic, epigenetic, and imaging). Finally, systems approaches need to be experimentally validated so they may be extended to translational and clinical applications.

Cancer systems biology will be essential to handle the influx of large and diverse data sets, including those generated in other NCI and NIH programs. Examples of NCI programs with large-scale data initiatives that are amenable to cancer systems biology approaches include the Cancer Target Discovery and Development (CTD2) program, the Clinical Proteomic Tumor Analysis Consortium (CPTAC), The Cancer Genome Atlas (TCGA) and the Physical Sciences-Oncology Network (PS-ON). Finally, at the national level, the President’s Science and Technology Priorities for the FY 2016 Budget calls for innovation in biomedical research through the specific development of systems biology initiatives.

CSBC Research Centers proposed in response to this FOA must demonstrate a systems biology approach to cancer research. This includes explicit integration of experimental biology and computational modeling to test and validate novel hypotheses or ideas. In addition to the major research component, each Research Center will also be required to develop and coordinate an outreach effort in cancer systems biology aligned with the research goals of the center and the CSBC.

This FOA invites a broad range of research that addresses important questions in cancer biology. Scientific questions should be of high importance and not readily addressable through other research mechanisms or initiatives due to their non-intuitive nature. Examples of such cancer-related issues that would require a systems biology effort might include, but are not limited to:

• Dynamic, predictive models that provide a robust and actionable understanding of the effect of multiple biological interactions and/or incorporate multi-scale, spatial analysis over varying resolution scales to describe cancer initiation, progression and metastasis.
• Models of networks and signal transduction pathways capable of predicting phenotypes in cancer, including but not limited to biochemical, statistical, graphical, logic, and relational modeling techniques. Phenotypes might be predicted at the molecular, cellular, tissue or organ level.
• Predicting and validating critical genetic and epigenetic changes in the initiation and progression of cancer.
• Modeling the molecular and cellular communication within and across cells of the tumor eco-system, including but not limited to the tumor micro-environment and the immune system.
• Integration of data obtained through new imaging modalities, such as super-resolution microscopy and cryo-electron microscopy (cryo-EM), into systems biology modeling frameworks to predict tumor phenotypes on multiple spatial scales.
• Prediction and validation of early disease indicators through systematic modeling of genetic factors and other high-risk disease phenotypes.
• Development of modeling techniques that span the scale between basic cellular mechanism and patient/population-level response or phenotype.
• In silico modeling to predict effective treatment. This includes predicting tumors most likely to benefit from a given treatment; converting transient responses into durable responses; and identifying rational combinations to address the emergence of resistance in future clinical trials.
• Systems analysis of cancer completed in endogenous settings (in vivo or ex vivo), with consideration of the tumor microenvironment, tumor heterogeneity, and tumor plasticity.

Each of the bullets above may require creation, incorporation, or utilization of novel experimental systems amenable to multivariate perturbation for the validation of cancer systems biology modeling efforts.

CSBC Research Center Expertise: This FOA requires that applicants assemble collaborating teams with expertise in cancer systems biology and cancer research. Due to the transdisciplinary nature inherent in systems biology projects and the focus on collaboration and expertise sharing, the CSBC Research Centers will require leadership having the ability to manage and understand the various approaches needed. Leadership and senior investigators of the team must have considerable expertise in the various aspects of cancer systems biology, especially cancer biology and mathematical/computational modeling.

Beyond the Research Center leadership, it is expected that the CSCB Research Centers will consist of an interdisciplinary research team of investigators with complementary expertise organized around a theme that addresses a fundamental question(s) in cancer research. The overall research theme should include one or more research areas, such as those described in the Research Objectives section above.

Each Center will consist of the following components:

• Administrative Core The CSBC Center Administrative Core will guide the organizing framework and connect the individual Center to the broader Consortium and the NCI. The members of the Administrative Core are expected to be the primary contacts for logistical and organization aspects of the Center (non-scientific activities) and for interaction with the CSBC and NCI program officials. Additionally, the Administrative Core will manage solicitation, review, and funding of Center pilot projects.
• Research Projects At the foundation of each CSBC Research Center will be high impact research projects that support the overall research theme. CSBC Research Centers will consist of a minimum of two to three Research Projects that integrate into the overall research theme and address complex and challenging questions in cancer research utilizing systems biology approaches.
• Shared Resource Core(s) While not required, Shared Resource Cores may be established to provide expertise and resources (e.g., imaging, technology, biological specimens, computational modeling, and mathematical theory development) that support multiple Research Projects.
• Outreach Core The required Outreach Core will coordinate scientific outreach activities that contribute to the overall research theme and expand the cancer systems biology community. The Outreach Core will operate both within the Center and across the Consortium primarily through the CSBC/PS-ON Coordinating Center (RFA-CA-15-015).

CSBC overall organization: The overall consortium will consist of funding initiatives solicited under three separate FOAs. All components will be governed by the CSBC Steering Committee with representatives from the funded CSBC Research Centers and U01 Projects, the CSBC Coordinating Center and NCI Program staff. Applicants are encouraged to read RFA-CA-15-015 for more information regarding the role of the U24 CSBC/PS-ON Coordinating Center. The CSBC will function as a collaborative network allowing Research Centers and Projects to cross-test ideas, integrate diverse data sets, and validate (or refute) theoretical, experimental, or clinical models.

Governance of the CSBC: The CSBC program, that includes CSBC U54 Research Centers, will be governed by the CSBC Steering Committee (see Section VI: Terms and Conditions of Cooperative Agreement.)

Evaluation of the Program: As the efficiency of the funded research is an important priority for NCI, CSBC Research Centers will be required to participate in an external evaluation process of the CSBC program coordinated by NCI Program Staff (see Section VI: Terms and Conditions of Cooperative Agreement.)

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.

Specific to this FOA:

Given the required expertise of the leadership in systems biology and in cancer biology research, this FOA encourages the use of the multi-PD/PI mechanism.

The CSBC Research Center PD/PI (contact PD/PI for applications with multiple PD(s)/PI(s)) must be a scientist with formal training and/or expertise in cancer systems biology, with contributions demonstrating substantial impact on the field.

The leadership team must also include an additional PD(s)/PI(s) or other senior investigator with appropriate primary expertise and substantial contributions in the field of cancer research.

(Additional PDs/PIs may be designated but are not required.)

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 can access 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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 and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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: Dan.Gallahan@nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
		Overall	12
Admin Core (use for Administrative Core)	6
Project (use for Research Projects)	12
Core (use for Shared Resources Core and Outreach Core)	6

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required, maximum of 1
• Research Projects: required, minimum of 2 and maximum 3
• Shared Resource Core(s): optional, maximum 2
• Outreach Core: required

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions. These additional instructions apply:

Project Summary /Abstract: Succinctly describe the overall research theme of the CSBC Research Center and how cancer systems biology approaches are paramount in accomplishing the research plan.

Project Narrative: State how the outcomes of the CSBC Research Center will further knowledge in the cancer research field and the potential impact they may have on public health.

Facilities & Other Resources: In addition to the information required in the standard instructions, highlight available facilities and/or services dedicated specifically to cancer systems biology approaches (e.g. high content screening, high-power computation, etc.). Indicate on what basis these resources will be available to the CSBC investigators (e.g., in-lab, freely available, fee-for-service, etc.).

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission applications (those that have previously submitted to this FOA), an Introduction to Application is required in the Overall component.

Specific Aims: State the overall vision and goals for the Center. The Specific Aims should be overarching, at a high level and distinct from the aims of the individual components.

Research Strategy: In this section, present a concise overall vision and plan for the proposed CSBC Research Center. The vision should focus on the plans for the funding period of the Research Center and may briefly highlight how the Research Center will lay the groundwork for longer-term plans. This section should describe the fundamental question(s) in cancer that will be addressed by the Research Center and how they integrate to form an overall research theme. Items to be addressed include:

• Research Theme. Define the overall research theme of the Research Center. Provide a brief background and rationale for this selection and outline the significance of research in the selected area.
• Research Center Organization. Provide a concise description of the structure of the Research Center and explain the following aspects: (1) how the skills of individual team members will translate into the collective capability of the center to accomplish the stated goals for transdisciplinary research and other activities; (2) your vision of the integration of the components into a Research Center as an entity that would be greater than the sum of its parts in terms of ability to advance fundamental question(s) in cancer research and, (3) how the elements of the Research Center, including key personnel, will interact to realize this vision.
• Research Projects. In a brief overview, outline the rationale for each project and the expected gains in terms of new knowledge advancing the research theme of the Center.
• Intra-center Pilot Projects. Briefly state how the intra-Center pilot projects will be incorporated into the efforts contributing to the overall Center research theme.
• Shared Resource Core(s) (If applicable). Briefly explain the need for any Shared Resource Core(s), indicating the specific Research Projects that will be supported by each Core. It is generally expected that a Shared Resources Core will support at least two research projects.
• Outreach Core. Briefly state the plans for Outreach programs that will advance the Research Center's program and cancer systems biology efforts.
• Research Center Scientific Integration. Explain how Center components (research projects and cores) will integrate and synergize. State how the Research Projects integrate to contribute directly to advancing the overall research theme of the Research Center. Applications should demonstrate that use of the U54 Center mechanism is essential to accomplishing goals that would not occur without the climate, facilities, and research resources that a Research Center can uniquely provide. Outline plans for intra-Center communication that will facilitate scientific integration.

Letters of Support: In addition to standard items, applicants must provide letters from the respective leadership official(s) in the institution(s) of the proposed center documenting specific institutional commitments to the proposed center.

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.
• The Data Sharing Plan should be provided only under the Overall component but it should cover all the activities of the Center.
• The plan should briefly describe the types of data, software, and models that are expected to be generated and shared, consistent with achieving the goals of the CSBC.
• Data, software, and models from this FOA are expected to be shared in an easily accessible format with the scientific community to increase the value of the significant public investment. Note that the NCI Program staff may negotiate modifications to these plans prior to funding. Specifically, applicants will be expected to abide by the data, software, and model sharing plan developed by the CSBC/PS-ON Coordinating Center and NCI program staff upon availability (see Section VI: Terms and Conditions of Cooperative Agreement).

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 preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• The CSBC Research Center PD/PI (contact PD/PI for applications with multiple PDs/PIs) must serve as the Administrative Core leader.
• If the multi-PD/PI model is not used, applicants must designate an appropriate senior investigator as an overall cancer research lead.
• The Administrative Core is expected to have a qualified Center Administrator to manage the day-to-day operations with responsibility for the administrative, budgetary, and operational aspects of the Center. For the Center Administrator, in the additional Senior/Key Profiles section, use Project Role of 'Other (Specify)' and provide the role under 'Other Project Role Category' as 'Center Administrator'.

Budget forms appropriate for the specific component will be included in the application package.

Leadership Effort Commitment: The CSBC Research Center contact PD/PI must commit and maintain through the life of the award a minimum of 2.4 person-month of effort. For other PDs/PIs, a minimum effort of 1.2 person-month per PD/PI is required. The required levels of effort may reflect an aggregate of the effort for the entire CSBC (listed here under Administrative Core) and the efforts for other CSBC components, as applicable.

Center Administrator. Based on the complexity of the CSBC Research Center, applicants are expected to propose and budget for a Center Administrator to manage day-to-day operations.

Funds for Intra-Center Pilot Projects: A minimum of $50,000 per year (direct costs) must be allocated to a fund for support of post-award pilot projects hosted within the Center.

Travel Funds: The budget should include funds to support travel for Center and Consortium activities, including but not limited to supporting the travel and participation of PD(s)/PI(s) and other CSBC Center members in the annual CSBC Investigators Meeting and annual site visits.

Other: Funds (including travel if appropriate) may be allocated for expenses related to the formation of an External Advisory Committee.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications (those that have previously submitted to this FOA), an Introduction to Application is allowed for each core.

Specific Aims: Outline Specific Aims for the Administrative Core.

Research Strategy: The Administrative Core is expected to have appropriate and effective administrative and organizational capabilities to: support cancer systems biology research and outreach; foster synergy and integration of the Research Center; and support planning and evaluation activities. Applications must describe the structure of the Administrative Core utilizing the following subsections (instead of the standard sub-sections):

Sub-section A. Center logistics and communication: Describe the strategies for communication across the Research Center leadership (multiple PD(s)/PI(s)) and key Research Center investigators, between project teams consisting of multidisciplinary investigators, and between the CSBC Research Center and the NCI. State who will be the lead for each level of communication. Provide a strategy for integration of new and early-stage investigators into the Research Center structure and environment.

Sub-section B. Intra-Center Pilot Projects: Describe how the Administrative Core will coordinate the solicitation, evaluation, and support of one-year intra-Center pilot projects. Indicate how pilot projects will be solicited and prioritized to ensure that they address and advance the overall research theme of the Research Center. Outline the evaluation process of the proposed pilot project, including specific details, e.g., what body/panel will review the application and who will be in charge of final project approval. Mention any anticipated follow up after a pilot project is selected for execution such as communicating details about funded pilot projects to NCI program staff, evaluation of project progress, options to terminate or change direction for non-performing projects, etc. Note: Do NOT propose any pilot projects in the application. However, the description may signal anticipated general directions and/or circumstances when pilot projects may be deemed particularly needed (e.g., the emergence of new knowledge or technology that creates a new opportunity to advance the theme of the Research Center but not covered by the full research projects).

Sub-section C. External Advisory Committee: Each awarded CSBC Research Center will recruit external experts (from outside of the Center) who will serve as scientific advisors to the CSBC Research Center leadership. Describe the general composition of the external advisory panel, the range of expertise to be sought, and how the panel will be expected to contribute to the Center's activities. However, to facilitate the review process, DO NOT name specific individuals in the application and DO NOT contact any potential candidates.

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.
• Resource Sharing Plans should only be included in the Overall component.

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.

When preparing your application in ASSIST, use Component Type Project.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project starting with "Project 1:", "Project 2:", etc.
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Projects)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Summary/Abstract: Provide an abstract/summary for the proposed Research Project, including how it fits within the research theme of the CSBC Center.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Projects)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Projects)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For projects with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of Other (Specify) and designate the role under 'Other Project Role Category' as Project Co-Lead and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in the additional Senior/Key Profiles section, use Project Role of Other (Specify) and provide the role under 'Other Project Role Category' as Project Co-Lead and provide a valid eRA Commons ID in the Credential field.
• Please note that Projects Leads and Project Co-Leads may be computational biologists, mathematicians, engineers and/or cancer researchers.

Budget (Research Projects)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Projects)

Introduction to Application: For Resubmission applications (those that have previously submitted to this FOA), an Introduction to Application is allowed for each project.

Specific Aims: State the specific aims of the Research Project and provide a rationale and description of how it fits into the research theme of the Research Center.

Research Strategy: The Research Projects constitute the most important activities of the Research Center and should focus on innovative approaches that integrate systems biology and cancer research perspectives to address fundamental question(s) in cancer research.

Applicants should utilize the standard structure of the Research Strategy section (i.e., sub-sections Significance, Innovation, and Approach).

Within these sub-sections, address the following additional aspects of each project:

• Provide a concise description of how the Project is integrated within the Research Center and contributes to the Research Center's overall research theme.
• State the multidisciplinary aspects of the Research Project and how it benefits from the unique scientific expertise of Research Center personnel.
• Indicate how the project team will take advantage of the Research Center infrastructure to allow for alternative approaches or perspectives to be quickly employed.
• Highlight any innovative systems biology approaches utilized within the project.
• If the Research Project will utilize the Shared Resource Core(s), describe how the Core(s) capabilities impact the proposed project.

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.
• Resource Sharing Plans should only be included in the Overall component.

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.

Planned Enrollment Report (Research Projects)

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

PHS 398 Cumulative Inclusion Enrollment Report (Research Projects)

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

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Shared Resource Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Core(s) starting with: "Core 1:","Core 2:"
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Shared Resource Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Shared Resource Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Shared Resource Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Shared Resource Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For Cores with multiple leads, in the Project Director/Principal Investigator section of the form, use Project Role of Other (Specify) and designate the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field. For other co-leaders, in the additional Senior/Key Profiles section, use Project Role of 'Other (Specify) and designate the role under 'Other Project Role Category' as 'Core Co-Lead' and provide a valid eRA Commons ID in the Credential field.
• Please note that Core Leads and Core Co-Leads may be computational scientists, mathematicians, physical scientists/engineers and/or cancer researchers.

Budget (Shared Resource Core)

Budget forms appropriate for the specific component will be included in the application package.

• The Core Lead(s) must each commit and maintain through the life of the award a minimum of 0.6 person-months per year of effort. If there are multiple Core Leads, it is not necessary that each commit equal effort to the project.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Shared Resource Core)

Introduction to Application: For Resubmission applications (those that have previously submitted to this FOA), an Introduction to Application is allowed for each core.

Specific Aims: In addition to outlining the specific aims of the Shared Resource Core, list which projects will be supported by the Shared Resource Core.

Research Strategy: The Shared Resource Cores may be physical or virtual infrastructures (e.g. cloud-based computing or storage) providing a biological, computational or engineering resource that supports other Center components in their activities. Each Shared Resource Core is expected to support two or more Research Projects and the services and resources provided to other Research Center components should be clearly defined. Issues to be addressed include, but are not limited to: value of the Core services to the Research Center and Research Projects, integration between the Core and Research Projects, quality control, procedures for selecting Research Projects to use the Core and allocating resources, cost effectiveness, and increased efficiency.

These proposed new shared resources must not duplicate analogous resources already established in the applicant institutions (although supplemental funding to such existing resources may be requested).

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.
• Resource Sharing Plans should only be included in the Overall component.

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.

Planned Enrollment Report (Shared Resource Core)

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

PHS 398 Cumulative Inclusion Enrollment Report (Shared Resource Core)

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

When preparing your application in ASSIST, use Component Type Core.

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

SF424 (R&R) Cover (Outreach Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: "Outreach Core"
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Outreach Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Outreach Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Outreach Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Outreach Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Outreach Core)

Budget forms appropriate for the specific component will be included in the application package.

A minimum of $100,000 direct costs per year must be allocated to the Outreach Core.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Outreach Core)

Introduction to Application: For Resubmission applications (those that have previously submitted to this FOA), an Introduction to Application is allowed for each core.

Specific Aims: Outline Specific Aims for Outreach Core.

Research Strategy: The Outreach Core will serve to promote cancer systems biology at all career stages and to disseminate advances and capabilities of cancer systems biology to the cancer research and broader communities. Identify and describe the outreach activities that will be undertaken by the Research Center. Include a plan to evaluate the effectiveness of the proposed outreach activities. The proposed activities should relate to the research theme of the Research Center. Potential activities include but are not limited to:

• Seminar series. Hosting of speakers that compliment the capabilities and advances of the CSBC.
• Workshops. Small focused meetings that bring together critical researchers in areas of cancer systems biology.
• Personnel Exchanges. Exchange of graduate students, postdoctoral fellows, or investigators within a Research Center or across the Consortium to facilitate the exchange of knowledge and ideas.
• Cross-training. Opportunities for early stage and established investigators in the various areas of systems biology to cross train within the CSBC or at NCI-funded programs.
• Center Website. Establishing a CSBC Research Center website to communicate the Research Center s mission, describe the availability of Research Center funding opportunities, and interface with the CSBC website.
• Research Center Annual Meeting. Dissemination of CSBC Research Center advances to the public or wider cancer research community through an open meeting.
• Think Tanks. Small meetings of investigators at all stages of career development to identify gaps in knowledge that contribute directly to the research theme of the Research Center.
• Research Center Newsletter. Publication of a Research Center newsletter that highlights research advances and promotes cancer systems biology in an open access environment.

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.
• Resource Sharing Plans should only be included in the Overall component.

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.

Planned Enrollment Report (Outreach Core)

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

PHS 398 Cumulative Inclusion Enrollment Report (Outreach Core)

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) using ASSIST or other electronic submission systems. 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.

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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: https://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 (SAM). 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 our Post Submission Application Materials policy.

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 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:

Reviewers will provide an overall impact score for the entire CSBC Center (Overall component) and for individual components of the Center [i.e., Administrative Core, Research Projects, Shared Research Core(s), and Outreach Core]. In addition, assigned reviewers will provide individual "criterion scores" for the Overall criteria and for the Research Projects criteria, but not for the other components.

For the evaluation of the CSBC Research Center application, the Research Projects will be assessed as the scientific base of each Center and its most important components, with additional components enhancing and integrating the overall research/outreach program. The overall impact score will reflect the synergy provided by inclusion of each CSBC Center component.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CSBC Center 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 Center 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 CSBC Research Center that by its nature is not innovative may be essential to advance a field.

Does the proposed CSBC Research Center address an important problem or a critical barrier to progress in the field? If the aims of the proposed CSBC Research Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: How well does the research theme of the proposed Research Center provide a systems biology and computational/mathematical modeling perspective of cancer that has the potential to address fundamental question(s) in cancer research? Do the overall research theme and the proposed activities (Cores, Research Projects) require a Center-based research structure for success? How well integrated are the individual components to form a CSBC Research Center that is greater than the sum of its parts?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the CSBC Research Center? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: Do the PD(s)/PI(s) (contact PD/PI for applications with multiple PD(s)/PI(s)) have adequate formal training or expertise in cancer biology and/or systems analysis/modeling? Does the CSBC Research Center leadership team have the appropriate breadth and balance of expertise? Do the Research Center PD(s)/PI(s) and other key personnel have the necessary specialized research expertise? How well does the expertise of the key personnel complement each other? How well do the proposed interactions and collaborations between the CSBC Research Center PD(s)/PI(s), Project Leads, and other key personnel unite the components and advance the science of the Research Center? How well does the proposed CSBC Research Center support and nurture a team science environment that can lead to important advances in cancer research?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA: How innovative is the proposed application of systems biology to questions in cancer research?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the proposed CSBC Research Center? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: How well does the overall research theme of the Research Center integrate perspectives and approaches from systems biology and cancer research to address fundamental question(s) in cancer research?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA: How well does the Research Center environment promote collaborations and transdisciplinary research?

Integration

Will the proposed Center be a truly integrated entity, rather than a collection of unrelated research projects and support services? How well does the CSBC Research Center organization promote scientific and administrative integration, synergy and a cohesive research program? Do the applicants state their willingness to collaborate and share models, software, and other resources within the CSBC Research Center and across the Consortium?

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

Significance

Does the Project address fundamental question(s) in cancer research from a systems biology and mathematical modeling perspective? Will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? How well does the Project advance the systems biology-based overall research theme of the Research Center?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise? Does the Project optimally utilize the combined multi-disciplined research expertise? How does the Project benefit from the unique scientific expertise of the Research Center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by applying systems biology and mathematical modeling based approaches and perspectives to cancer research? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? How well does the Project integrate perspectives and approaches from systems biology and mathematical modeling to address fundamental question(s) in cancer research? Does the Project approach integrate into the research theme of the Research Center?

If the Project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

How well does the Project environment promote collaborations and transdisciplinary research? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment of the Center, subject populations, or collaborative arrangements?

Reviewers will provide only one overall impact score for the Administrative Core (criterion scoring is not used for this component). Reviewers will consider the following criteria to determine an impact score:

• Does the CSBC Research Center Administrative Core team have the appropriate expertise to manage logistics and communication within the Research Center?
• Is the plan for intra-Center pilot project solicitation, review, and funding fair and sensible?
• Are the anticipated scope of expertise and modus operandi of an External Advisory Committee to be formed appropriate for the needs of the proposed Research Center?

Reviewers will provide only one overall impact score for the Outreach Core (criterion scoring is not used for this component). Reviewers will consider the following criteria to determine an impact score:

• Are there sufficient and appropriate technical and scientific expertise, mentoring experience, and available faculty and staff to conduct the proposed outreach activities?
• How well will the proposed outreach activities prepare investigators at all career levels for working at the interface of computational science and cancer research?
• How well will the proposed outreach activities promote the broader dissemination of cancer systems biology research?
• How well do the proposed outreach activities relate to and integrate with the research theme of the Research Center?
• Are the plans for evaluating the proposed outreach activities suitable?

Reviewers will provide only one overall impact score for the Shared Resource Cores (criterion scoring is not used for this component). Reviewers will consider the following criteria to determine an impact score:

• How well matched is the proposed Shared Resource Core to the needs of the overall Research Center? Are the services of the Shared Resource Core essential to the goals of more than one Research Project?
• Are the qualifications, experience, and effort commitment of the Shared Resources Core Director(s) and other key personnel adequate and appropriate for providing the proposed facilities or services?
• Will the proposed Shared Resource Core provide cost effective services to the Research Center, prevent duplication, and/or increase efficiency?
• What is the overall quality level of the proposed Core services and technologies and the rigor of processes for quality control/quality assurance?

As applicable for the 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 CSBC Research Center 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 CSBC Research Center 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 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.

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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 Part 75.

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:

• Overseeing the scientific research in the Research Center, analyzing and interpreting research data, reporting results to the scientific community, and disseminating approaches, methods, models, software, and tools broadly.
• Committing and maintaining throughout the life of the CSBC Research Center a minimum of 2.4 person-months of effort per year for each 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.
• Agreeing to be an active participant in the CSBC, including attending the Annual Investigators Meeting, participating in other consortium sponsored meetings and workshops, and participating in collaborative activities.
• Promoting trans-CSBC and external collaborations to advance cancer systems biology research.
• Serving on the CSBC Steering Committee. The CSCB Research Center PD(s)/PI(s) (contact PD/PI for applications with multiple PD(s)/PI(s)) are required to serve as members of the Steering Committee.
• Abiding by the governance of the CSBC and all program policies agreed upon by the CSBC Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations.
• Reporting progress to the NCI Program Officials on all CSBC Research 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 members on a semi-annual basis.
• Being prepared for the annual site visits of NCI Program staff members and participation in the NCI-coordinated evaluation of the CSBC program. The Administrative Core should coordinate participation in Research Center program evaluation activities, including progress reports, site visits, and formation of an external advisory committee.
• Ensuring that data are deposited in a timely manner in appropriate publicly available locations, and that models, software, and other tools and resources developed as part of this Research Center are made publicly available according to CSBC policies. Additionally, all CSBC Research Centers will be required to utilize the Resource Coordinating Hub, a resource to be developed by the CSBC/PS-ON Coordinating Center that will be funded under the companion FOA RFA-CA-15-015.
• Ensuring that results of the Research Projects are published in a timely manner.
• Organizing scientific working groups to facilitate collaborative projects and cross-testing of experimental and theoretical concepts.
• Notifying NCI Program staff members about intra-Research Center pilot projects (those funded through restricted funds in the Administrative Core) selected for execution (with information on the scope of these projects and how they can contribute to the overall research theme of the Center).

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. Participating CSBC Research Center members are also encouraged to organize and participate in other Consortium meetings and workshops, organize collaborative activities, and promote Trans-Consortium collaborations, and organize and participate in scientific and programmatic working groups.

NIH staff will 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 of the CSBC Steering Committee.
• Assisting the Steering Committee, the CSBC/PS-ON Coordinating Center, and individual U54 and U01 awardees in avoiding unwarranted duplications of effort across the CSBC.
• Facilitating collaborative research efforts that involve multiple CSBC Research Centers and would be suitable for consideration by the Collaboration and Pilot Project Hub to be managed by the U24 Coordinating Center.
• 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 take advantage of existing NIH/NCI resources and infrastructures. This will specifically include acting as a liaison between the CSBC and PS-ON.
• 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.
• Monitoring the operations of the CSBC awardees and making recommendations on overall project directions and allocations of CSBC Center funds.
• Reviewing the progress of the CSBC awardees (including CSBC/PS-ON Coordinating Center), conducting periodic site visits, and taking other actions as needed.
• Participating in organizing annual CSBC meetings, specialized workshops, and webinars of the consortium.
• 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:

The CSBC will have a Steering Committee as a governing body. The CSBC Steering Committee will consist of:

• 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 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 Steering Committee may have additional non-voting members. The contact PD/PI of the awarded CSBC/PS-ON Coordinating Center (U24) will be a permanent non-voting member.

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.
• 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.

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.

In addition to standard information, the annual report must include (under Administrative Core component, Section B "Accomplishments") the following information:

• Details pertaining to the outcomes of each intra-Center pilot project; and
• A summary of the outcomes associated with each trans-Network pilot project, in which a given Research Center is involved.

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: https://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 Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Dan Gallahan, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6180
Email: Dan.Gallahan@nih.gov

NCI Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: hines@mail.nih.gov

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.