Metabolic Reprogramming to Improve Immunotherapy (R01)

Metabolic Reprogramming to Improve Immunotherapy (R01) is sponsored by National Cancer Institute (NCI). This funding opportunity aims to generate a mechanistic understanding of metabolic processes supporting anti-tumor immune responses in vivo, determine how the metabolic landscape of the tumor microenvironment affects immune effector functions, and use this information to manipul…

Expired PAR-16-228: Metabolic Reprogramming to Improve Immunotherapy (R01) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Cancer Institute ( NCI ) Funding Opportunity Title Metabolic Reprogramming to Improve R01 Research Project Grant Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research.

See Notice Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128 . November 26, 2018 - NIH & AHRQ Announce Upcoming Updates to Application Instructions and Review Criteria for Research Grant Applications.

See Notice NOT-OD-18-228 . Reminder: FORMS-E Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2018. - Updates to Active Funding Opportunity Announcements to Prepare for Policy Changes Impacting Due Dates On or After January 25, 2018.

May 10, 2017 - New NIH "FORMS-E" Grant Application Forms and Instructions Coming for Due Dates On or After January 25, 2018. See NOT-OD-17-062 . Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity PAR-16-229 , R21 Exploratory/Developmental Grant Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose The overall goal of this funding opportunity announcement (FOA) is to encourage R01 grant applications to (a) generate a mechanistic understanding of the metabolic processes that support robust anti-tumor immune responses in vivo, (b) determine how the metabolic landscape of the tumor microenvironment affects immune effector functions, and (c) then use this information to manipulate (reprogram) the metabolic pathways used by the tumor, the immune response, or both to improve cancer immunotherapy.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) dates , by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

The first standard application due date for this FOA is Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date. AIDS Application Due Date(s) AIDS dates apply, by 5:00 PM local time of applicant organization.

All types of AIDS and AIDS-related applications allowed for this funding opportunity announcement are due on these dates. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in (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 I.

Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Full Text of Announcement Section I.

Funding Opportunity Description The overall goal of this FOA is to encourage research grant applications to (a) generate a mechanistic understanding of the metabolic processes that support robust anti-tumor immune responses in vivo, (b) determine how the metabolic landscape of the tumor microenvironment affects immune effector functions, and (c) then use this information to manipulate (reprogram) the metabolic pathways used by the tumor, the immune response, or both to improve cancer immunotherapy.

This FOA utilizes the Research Project Grant (R01) mechanism. , which supports research applications that propose to investigate novel scientific ideas, model systems, tools, agents, targets, and technologies that have the potential to substantially move the field forward.

This FOA runs in parallel with an FOA of similar scientific scope, PAR-16-229 , which utilizes the Exploratory/Developmental Grant (R21) mechanism One the critical pathways that enables growth and survival of cancer cells is the ability to reprogram metabolism from primarily oxidative phosphorylation (OxPhos) observed in normal resting cells to aerobic glycolysis (Warburg metabolism).

This reprogramming is associated with an increase in glucose receptor expression, glucose uptake, diversion of glycolytic intermediates to various biosynthetic pathways required for tumor cell growth, and the export of lactate and other metabolites that alters the metabolic landscape of the tumor microenvironment. Similarly, reprogramming of lipid metabolism in tumor cells can contribute to cell survival and clonal expansion.

Metabolic changes in the tumor can also deprive tumor-infiltrating immune cells of essential nutrients and metabolites required for effective responses to the tumor, contributing to immunosuppression in the tumor microenvironment. Recent advances in immunology have demonstrated that lymphocytes undergo a similar reprogramming to Warburg metabolism to meet the demands of clonal expansion following antigen stimulation.

Whereas na ve T cells generate ATP through OxPhos to maintain basic cellular functions (ion transport, membrane maintenance, and protein turnover), following exposure to antigen they switch to Warburg metabolism. Altered regulation of lipid metabolism in lymphocytes upon activation can also have critical and pleiotropic effects on cell fate and function.

Such inter-connected metabolic shifts are thought to play critical roles in lymphocyte activation, clonal expansion, lineage differentiation and acquisition of effector functions, and generation of long-lived memory T cells capable of self-renewal.

The presence of memory cytotoxic T cells in tumors is associated with an optimum anti-tumor immune response, suggesting that manipulating metabolic pathways to generate more memory CTL could dramatically enhance anti-tumor immune responses.

However, in order to capitalize on these advances to improve cancer immunotherapy we need to understand more fully how metabolic pathway choice affects lymphocyte differentiation into specific effector subsets and how the immune system is affected by the altered metabolic landscape of the tumor microenvironment in which the nutrient/metabolite pools and environmental conditions (such as hypoxia and acidosis) have been dramatically altered by the metabolic state of the tumor.

At present we don t fully understand the similarities, differences, and functional consequences of the metabolic pathways utilized by activated immune cells and cancer cells that would guide the development of novel metabolic interventions to improve immunotherapy.

Specific Research Objectives Critical needs for future studies include developing (a) approaches to reprogram the metabolic qualities of anti-tumor immune cells (either ex vivo or in vivo) to improve immunotherapy (homing, persistence and/or effector function), and/or (b) approaches that target cancer cell metabolic pathways to impair cancer cell survival without compromising endogenous Applicable research directions could include, but not be limited to, the following: Challenges and Opportunities: Assess the crosstalk between the different metabolic platforms that may be operating in any given cell and integrate those assessments to generate a more complete metabolic profile at the single cell level.

Generate a better understanding of metabolites as signaling molecules in transcription that effect cellular differentiation. Determine the relationship between metabolism and self-renewal Clarify how specific metabolites affect various immune states such as activation, anergy, development of long-lived memory cells versus short-lived effector cells, and homing to their proper niche.

Elucidate how the metabolic environment (or nutrient repertoire) in normal tissues, immune tissues, and in the setting of pathology (in tumors) affects immune cell development and/or effector function. Delineate the consequences of metabolic interventions on immune cell growth and effector functions. New instrumentation and novel approaches are needed to parse the metabolic heterogeneity of tissues in situ.

Improved methods and approaches need to be developed to assess characteristics of the tumor microenvironment affect the anti-tumor immune response. Computational models to better understand which metabolic pathways are hard-wired and when perturbed lead to cell death and which are flexible and can be experimentally manipulated need to generated.

Development of small molecule inhibitors of glycolysis, FAO, and other metabolic pathways for therapeutic intervention is needed. The ability to perform comprehensive analysis of the metabolic heterogeneity (metabolic flux/metabolomics) of different immune subsets and a full description of the functional consequences of differential utilization of metabolic pathways in supporting immune cell differentiation is needed. See Section VIII.

Other Information for award authorities Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Clinical Trials Not Allowed for due dates on or after January 25, 2018: Only accepting applications that do not propose clinical trials Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project. The maximum project period is 5 years.

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: o Hispanic-serving Institutions o Historically Black Colleges and Universities (HBCUs) o Tribally Controlled Colleges and Universities (TCCUs) o Alaska Native and Native Hawaiian Serving Institutions o Asian American Native American Pacific Islander Serving Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Institutions) Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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 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 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. Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

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 must have an active DUNS number and SAM registration in order to complete the 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.

Eligible Individuals (Program Director/Principal 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 This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3.

Additional Information on Eligibility 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 A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 ). Section IV. Application and Submission Information Applicants must obtain 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 . 2. Content and Form of Application Submission It is critical that applicants follow the instructions in (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 For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant All page limitations described in the SF424 Application Page Limits must be followed.

Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an All instructions in the SF424 (R&R) Application Guide SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Do not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) Application PHS Inclusion Enrollment Report When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 PHS Human Subjects and Clinical Trials Information Form only available in FORMS-E application packages for use with due dates on or after January 25, 2018.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions: If you answered "Yes" to the question "Are Human Subjects Involved?"

on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed. PHS Assignment Request Form All instructions in the SF424 (R&R) Application Guide Foreign (non-U.S.) institutions must follow policies Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide. 3.

Unique Entity Identifier and System for Award Management (SAM) See Part 1. Section III. 1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Part I.

Overview Information contains information about Key Dates and times. 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. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next 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 and time.

If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application 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. 5. Intergovernmental Review This initiative is not subject to intergovernmental 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 . 7. Other Submission Requirements 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 Electronically . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must for Applicants Experiencing System Issues .

For assistance with application submission, contact the Application Submission Contacts in Section VII . 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, NIH.

Applications that are incomplete or non-compliant will Requests of $500,000 or more for direct costs in any year Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 Post Submission Materials Applicants are required to follow our Post Submission Application Materials policy.

Section V. Application Review Information Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019. 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 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 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. Does the project address an important problem or a critical barrier to progress in the field?

Is there a strong scientific premise for the project? If the aims of the project 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?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators those 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? 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? Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?

Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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?

Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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?

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?

Additional Review Criteria 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.

Protections for Human Subjects 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 Inclusion of Women, Minorities, 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 The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals.

Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. 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 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 For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project.

If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations 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.

Applications from Foreign Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 (GDS) .

Authentication of Key Biological and/or Chemical Resources: For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources. Budget and Period of Support 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 Center for Scientific Review, 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 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 Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board.

The following will be considered in making funding decisions: Scientific and technical merit of the proposed project as determined by scientific peer review. Relevance of the proposed project to program priorities. 3.

Anticipated Announcement and Award Dates After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) Commons . Refer to Part 1 for dates for peer review, advisory council review, and earliest start date. Information regarding the disposition of applications is available Grants Policy Statement .

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