NIDDK (Re)Building a Kidney Consortium (UH2/UH3)

NIDDK (Re)Building a Kidney Consortium (UH2/UH3) is sponsored by National Institutes of Health (NIH) / National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This FOA invites new research project applications to participate in the NIDDK (Re)Building a Kidney Consortium, a research network focused on expanding tools, resources, and knowledge to guide studies on in vivo regeneration of functional nephrons or in vitro generation of neph…

Expired RFA-DK-14-010: (Re)Building a Kidney: Cells to Organ (UH2/UH3) 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 Institute of Diabetes and Digestive and Kidney Funding Opportunity Title (Re)Building a Kidney: Cells to Organ (UH2/UH3) UH2 / UH3 Phase Innovation Awards Cooperative Agreement July 22, 2019 - This RFA has been reissued as RFA-DK-19-007 . November 26, 2014 - See Notice NOT-DK-15-004 .

Notice of Pre-application Webinar for RFA-DK-14-009 "(Re)Building a Kidney Coordinating Center (U01)" and RFA-DK-14-010 "(Re)Building a Kidney: Cells to Organ (UH2/UH3)" September 25, 2014 - See Notice NOT-DK-14-026 .

Notice of Change to the Award Budget for RFA-DK-14-010 "(Re) Building a Kidney: Cells to Organ (UH2/UH3)" Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity RFA-DK-14-009 ; U01 Cooperative Agreements Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose This Funding Opportunity Announcement (FOA) invites new research project applications to participate in the NIDDK (Re)Building a Kidney Consortium.

The projects will be part of a research network focused on the expansion of tools, resources, and knowledge that will guide studies on the in vivo regeneration of functional nephrons or in vitro generation of nephrons for kidney transplant. Funds will be made available through the UH2/UH3 cooperative agreement award mechanism.

The initial UH2 phase will support milestone-driven projects that will inform strategies for the enhancement of endogenous regenerative repair processes and generation of cell types important for the development of functional nephrons. UH2 projects that have met their scientific milestones will be eligible for transition to the second UH3 phase after NIH administrative review.

The UH3 award is to provide a second phase for the support for innovative exploratory and development research activities initiated under the UH2 mechanism. UH3 phase will support milestone-driven projects. It is anticipated that relevant projects will be integrated as appropriate to further synergistic interactions and collaborations.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) January 14, 2015, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date. 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) 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 Section 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 This Funding Opportunity Announcement (FOA) invites new research project applications to participate in the NIDDK (Re)Building a Kidney Consortium.

The goals of this initiative are to establish a network of investigators and research projects focused on the expansion of tools, resources, and knowledge that will guide studies on the in vivo regeneration of functional nephrons or in vitro generation of nephrons for kidney transplant.

To maximize scientific exchange and accelerate this area of research, the (Re)Building a Kidney Consortium will include a Coordinating Center that will facilitate activities of the consortium and oversee communication of data, and sharing of resources and tools within the consortium and the research community. The Coordinating Center is being considered under RFA-DK-14-009 "(Re)Building a Kidney Consortium Coordinating Center (U01)".

Chronic Kidney Disease (CKD) and Acute Kidney Injury (AKI) are interconnected syndromes which pose a substantial public health burden. Even with the best available medical therapy, the progressive loss of kidney function can lead to need for renal replacement therapy (dialysis, kidney transplantation), both of which have substantial morbidity and mortality.

While living donor kidney transplantation is preferred, the selection process is complex and lengthy, not all patients are candidates, organs are in short supply, and two surgeries are required (donor and recipient).

Unlike dialysis, kidney transplantation cannot be offered Currently few efforts have been successful in ameliorating the acute injury in AKI, and chronic progressive pathologic processes in CKD, although the use of agents which interrupt the renin-angiotensin-aldosterone system have improved the care of patients with CKD.

Progressive kidney disease involves failure to effectively repair injury, ineffective regeneration of critical tissues, and unchecked continuation of pathophysiologic processes. Hence, the development of potential alternative therapies is of great importance.

The development and employment of strategies to enhance renal repair and promote the generation of new nephrons in the postnatal organ could have a significant impact on the prevalence and progression of kidney disease. The de novo repair of nephrons, the re-generation of nephrons, and the in vitro engineering of a biological kidney all require diverse scientific approaches drawn from several disciplines and lines of study.

This includes, but is not limited to, studies in developmental and cellular biology, productive and maladaptive repair, stem and progenitor cell biology, and tissue engineering. However, the cross-talk between these disciplines is limited.

Although our understanding of the establishment, maintenance, and differentiation of the renal progenitors is extensive, only recently has this knowledge been used to guide the in vitro induction of renal cell lineages. It has not been exploited to inform strategies to best re-cellularize an injured kidney.

Ongoing studies and new developments have produced detailed knowledge of nephron development, induction of pluripotent stem cells towards a renal cell fate, and ex-vivo programming of renal progenitor cells. These advances make it reasonable and timely to consider efforts to coordinate and support studies that will in the future culminate in the ability to generate or repair nephrons that can function within the kidney.

This program will be funded in two phases.

During the UH2 phase, the NIDDK will support a wide range of projects including but not Identify, characterize, and evaluate progenitor cell types (embryonic and in the adult), including manipulation of iPS cells to a renal Determine the role of microenvironments to establish the cellular compartments of the kidney (including innervation, and the vasculature and Study progenitor cells and microenvironment involved in productive repair in response to injury; Develop and study scaffolds for use both in vivo and in vitro; Evaluate methods to target cells and molecules to specific kidney locations/compartments; and Establish the necessary pre-patterning of the kidney and the interaction of cellular components to boost kidney self-organization.

It is anticipated that the identification of progenitor cells, their microenvironment, and understanding the differentiation of renal and associated cell types and the development of scaffolds will spin-of key insights and reagents that can be utilized in the UH3 phase.

UH3 phase should focus on studies that may (1) increase nephron number or nephron efficiency in situ to increase kidney capacity (2) allow kidney organogenesis in vitro, including cellular re-population of kidney scaffolds, (3) enhance productive repair thru manipulation of endogenous or exogenous cells, or (4) develop functional renal organoids or establish large scale cell cultures for purification of specific Transition to the UH3 phase will be based on an administrative review.

The criteria to advance to the UH3 phase will be based Successful achievement of the defined milestones for the UH2 Potential for meeting the UH3 phase stated goals; Ability to work within a consortium arrangement and with other UH2 awardees to meet the goals of the initiative; Availability of funds; and Applications unresponsive to this FOA are those that focus primarily on basic transcriptional control of renal cell development, characterization of kidney injury models, creation of patient-derived hPSC lines, development of in vitro or in vivo disease models for studying pathophysiology, identification of therapeutic drug compounds or construction of artificial or bio-artificial dialyzers.

Non-responsive applications will not proceed to review. The (Re)Building a Kidney Consortium will be made up of awardees involved in the (Re)Building a Kidney research projects as proposed in this FOA, the (Re)Building a Kidney Coordinating Center, the Opportunity Pool studies as described in RFA-DK-14-009 . The Consortium will be a collaborative effort between the awardees and the NIDDK.

NIDDK will request that applicants share with members of the ((Re)Building a Kidney Consortium and its External Advisory Panel their peer review evaluation, post award evaluation, and their submitted application in response to this FOA.

In addition, prior to publication but upon validation (1) all tools, reagents and data will be shared with consortium members, and (2) all tools and reagents will be made available to the general research community. Section II. Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards NIDDK intends to commit a total of $3 million in FY 2015 for RFA-DK-14-009 and RFA-DK-14-010. The UH2 phase will support between 6-8 awards.

Following administrative review, it is anticipated that the UH3 phase will support between 4-6 awards made up of successful UH2 projects. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. The direct costs for UH2 awards are expected to be approximately $200,000-$300,000 per year.

Total costs for the entire UH2 phase are limited to $500,000. For the UH3 phase, the direct cost amount is expected to be approximately $500,000-$600,000. Total costs for the UH3 phase are limited to $1.

0 million per year. The UH2 phase is limited to two years. The UH3 phase is limited to three years.

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: Black Colleges and Universities (HBCUs) Controlled Colleges and Universities (TCCUs) Native and Native Hawaiian Serving Institutions 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 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 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 to 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 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 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. Applicants must have an active DUNS number and SAM registration in order to complete the Grants. gov registration.

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 (R&R) Application Guide.

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 ). In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows.

The NIH will accept submission: To an RFA of an application that was submitted previously as an investigator-initiated application but not paid; Of an investigator-initiated application that was originally submitted to an RFA but not paid; or Of an application with a changed grant activity code. Section IV.

Application and Submission Information Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions 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 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 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, preferably electronically, should be Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 6707 Democracy Boulevard, Rm.

752 MSC 5452 (for express/courier service: Bethesda, MD 20817) All page limitations described in the SF424 Application Page Limits must be followed.

The Biographical Sketch for each Senior/Key Person may not 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 Attachments: Please provide a statement indicating willingness Work with NIDDK to participate in the initial and semi-annual meetings during the course of the grant award; Cooperatively interact with NIDDK in support of the projects and Actively seek input from NIDDK regarding resource or expertise needs that may arise during the performance of the project; and Participate in monthly conference calls.

SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide Sketch: NIDDK is piloting a proposed change to the SF424 (R&R) Biographical Sketch to allow applicants to this FOA to include a description of up to five contributions to their scientific field(s). The Biographical Sketch Format page for the pilot is available at http://grants. nih.

gov/grants/funding/424/SF424R-R_pilot-biosketch_VerC. docx . Following the education section of the Biographical Sketch, complete sections A, B, C and D as indicated below: NOTE: Applicants must follow the format and instructions A.

Personal Statement: Briefly describe why you are well-suited for your role in the project described in this application.

The relevant factors may include aspects of your training; your previous experimental work on this specific topic or related topics; your technical expertise; your collaborators or scientific environment; and your past performance in this or related fields (you may mention specific contributions to science that are not included in Section C).

Also, you may identify up to four peer reviewed publications that specifically highlight your experience and qualifications for this project, provided that those publications do not appear in Section C. If you wish to explain impediments to your past productivity, you may include a description of factors such as family care responsibilities, illness, disability, and active duty military service. B.

Positions and Honors: List in chronological order previous positions, concluding with the present position. List any honors. Include present membership on any Federal Government public advisory committee.

C. Contributions to Science: Briefly describe up to five of your most significant contributions to science. For each contribution, indicate the historical background that frames the scientific problem; the central finding(s); the influence of the finding(s) on the progress of science or the application of those finding(s) to health or technology; and your specific role in the described work.

For each of these contributions, reference up to four peer-reviewed publications that are relevant to that contribution. The description of each contribution should be no longer than one half page including any figures. Please also provide a link to a full list of your published work as found in a publicly available digital data base such as PubMed, myBibliography, or SciENcv all of which are maintained by the National D.

Research Support: List both selected ongoing and completed research projects for the past three years (Federal or non-Federally-supported). Begin with the projects that are most relevant to the research proposed in the application. Briefly indicate the overall goals of the projects and responsibilities of the key person identified on the Biographical Sketch.

Do not include number of person months or direct costs. All other components of the Biographical Sketch remain as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide Budget requests must include costs for the PD/PI and at least one other member of the individual project to attend the initial and 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: Aims: The UH2 and UH3 phases should have distinct and clearly enumerated specific aims; both phases should be included in a single specific Strategy: The research strategy section should include sections succinctly addressing how the tools, resources, and knowledge developed in the UH2 phase will be used to direct the UH3 phase; and how development of the UH3 phase will guide strategies for the generation or enhanced repair of nephrons or enhancement of clinical treatment.

A section labeled Milestones must be included for both the UH2 and UH3 phases. Milestones are different from specific aims. The milestones must provide objective and quantitative outcomes by which to justify advancing the project.

For the UH2 phase of the application, milestones must address the critical tools, resources or knowledge to be generated. Milestones for the UH3 phase must address utilization of advancements in the UH2 phase to advance critical areas outlined for UH3 Phase in Section I. Funding Opportunity Description.

The application must include a strong rationale for the choice of models, functional readouts, and quantitative go/no-go decisions to be made by those involved in the project, based upon accepted practices in the specific field. Once an application is funded, the milestones will be used to evaluate progress as part of the non-competing award process.

Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) 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 the Resource Sharing Plan.

All applications are expected to provide plans that address sharing and demonstrate commitment to make data, biomaterials, models, reagents, tools, resources and methods available to the (Re)Building a Kidney Consortium and the research community.

The terms and timelines for sharing within the (Re)Building a Kidney Consortium; adjustments for coordination of research plans, validation of models, materials, methods and data; and sharing with the research community will be established by the Steering Committee consistent with achieving the goals of the program and NIH policies and all participants are expected to adhere to these terms as a condition of award.

The sharing plan must include an agreement that investigators will work collaboratively with the (Re)Building a Kidney Consortium and with the Coordinating Center to maximize research accomplished by the consortium, and to implement procedures to provide quality controlled (per Steering Committee-approved procedures) data and information In addition, applications are expected to include plans for the form and method to make resources, materials and models available to other investigators, for example through public resource centers, consistent with achieving the goals of the program.

These plans should address releasing data and information validated per Steering Committee policies, and make materials and resources available to the research community in accordance with Steering Committee policies and prior to publication of the research results.

This plan should also address methods for continuing to make public (Re)Building a Kidney Consortium data available to the NIH and the research community upon completion or termination of the project so that accumulated data remain accessible, for example through public repositories if available. Do not use the Appendix to circumvent page limits.

Follow all instructions for the Appendix as described in the SF424 (R&R) Planned Enrollment Report When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) PHS 398 Cumulative Inclusion Enrollment Report When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement , and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide. Part I. Overview Information contains information about Key Dates.

Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies).

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants. gov systems check the application against many of the application instructions upon submission.

Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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. 4.

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 Pre-award costs are allowable only as described in the NIH Grants Requirements and Information 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 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. tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Applications that are incomplete and/or nonresponsive will not be reviewed. In order to expedite review, applicants are requested to notify the NIDDK Referral Office by email at [email protected] when the application has been submitted.

Please include the FOA number and title, PD/PI name, and title of the application. Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030 . Section V.

Application Review Information 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 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?

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?

Does the research address a critical need in advancing the tools, resources or knowledge necessary to guide strategies for the in vivo regeneration of functional nephrons to enhance repair or in vitro generation of nephrons for a transplantable kidney? 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 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?

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? Is the overall approach to sharing adequate to allow timely distribution