Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations


National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title

Consortium of Lung Repair and Regeneration: Building the Foundation (U01)

Activity Code


U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices
  • December 7, 2010 - FAQs have been developed for RFA-HL-12-006 and RFA-HL-12-010. See NOT-HL-11-135.
Funding Opportunity Announcement (FOA) Number

RFA-HL-12-006

Companion FOA

RFA-HL-12-010

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestics Assistance (CFDA) Number(s)

 93.838   

FOA Purpose

The National Heart, Lung, and Blood Institute (NHLBI) invites applicants to participate in the Lung Repair and Regeneration Consortium (LRRC).  The goal of the Consortium is to bring together multidisciplinary teams of investigators, cutting edge technologies, innovative strategies, and new ideas to catalyze research on lung regeneration and repair. The Consortium will contain collaborative research support and skills development components to be administered after the Consortium is assembled. The purpose of this FOA is to attract new expertise into multidisciplinary teams to investigate novel hypotheses relevant to lung repair/regeneration and to develop a highly interactive and synergistic Consortium of investigators who will share ideas, data, and resources to move the field of lung regeneration forward toward development of new therapies for human diseases. This FOA solicits Research Project Cooperative Agreement (U01) applications from institutions/organizations that propose (1) to apply novel technologies to test innovative hypotheses of mechanisms that control adaptive and maladaptive lung repair/regeneration after injury and include studies to validate these mechanisms are relevant in humans; and (2) to develop two or more novel tools (e.g., reagents, models, imaging, and/or data analysis tools) that would accelerate research progress in lung regeneration.  Applicants are strongly encouraged to use the multiple Principal Investigator mechanism to organize multidisciplinary teams that must include new collaborations and expertise in two or more of the following disciplines:  developmental biology, stem cell biology, pulmonary medicine, lung injury, physiology, genomics, tissue or bioengineering, nanotechnology, and integrative, systems approaches.     

Key Dates
Posted Date
Open Date (Earliest Submission Date)

Not Applicable

Letter of Intent Due Date

January 10, 2011

Application Due Date(s)

February 10, 2011, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

August 2011

Advisory Council Review

October 2011

Earliest Start Date(s)

December 2011

Expiration Date

February 11, 2011

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of 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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Research Objectives

The National Heart, Lung, and Blood Institute (NHLBI) invites applicants to participate in the Lung Repair and Regeneration Consortium (LRRC).  The goal of the Consortium is to bring together multidisciplinary teams of investigators, cutting edge technologies, innovative strategies, and new ideas to catalyze research on the mechanisms of lung regeneration and repair, and to develop new tools, reagents, and models to elucidate the lung’s capacity for regeneration.  The Consortium will also contain collaborative research support and skills development components to be administered after the Consortium is assembled through the companion FOA, RFA HL-12-010 " Lung Repair and Regeneration Consortium (U01) Administrative Coordinating Center " in years 2-5. The purpose of this FOA is to develop a highly interactive and synergistic Consortium of investigators who will share ideas, data, and resources to move the field of lung regeneration forward toward development of new therapies for human diseases. This FOA solicits Research Project Cooperative Agreement (U01) applications from institutions/organizations that propose 1) to test innovative hypotheses of mechanisms that control adaptive and maladaptive lung repair/regeneration after injury and include studies to validate these mechanisms are relevant in humans and 2) to develop two or more novel tools (e.g. reagents, models, imaging, and/or data analysis tools) that would accelerate research progress in lung regeneration.  LRRC Research Centers will be comprised of multidisciplinary teams that will work collaboratively with other Research Centers in the LRRC to accelerate science in lung repair and regeneration.

Collaboration and interaction between LRRC investigators will be a requirement of the program. The LRRC will be responsible for collaboratively generating, validating, and sharing necessary reagents, models, antibodies, assays, protocols, and technologies that are beyond the scope of any single research effort with the goal of accelerating lung repair/regeneration research specifically, but also the potential to advance basic research in general.  These tools and reagents will be rapidly shared with members of the Consortium, and eventually advertised and made available on a public website developed by the Administrative Coordinating Center. 

Background

The lung is exposed to many potentially injurious insults with resultant responses that can either restore/maintain lung function or lead to irreversible remodeling and dysfunction.  Mechanisms of lung repair/regeneration are being explored in a variety of models, but new technologies and approaches are needed to bring important progress and fresh hypotheses to this complex and challenging area of pulmonary research.  Exploration of regenerative strategies is well underway for organ system disorders such as neurodegenerative diseases, trauma to skin and bones, and for blood and heart diseases, but have not been leveraged to expand understanding of the unique aspects of regeneration of the lung. Previous studies have revealed that stem/progenitor cells differ by lung compartment, key stem cell signaling molecules, such as Wnt, can affect multiple cellular processes that may be antagonistic during tissue repair (progenitor expansion vs. fibrosis), and that lung regeneration and repair responses are maturation-dependent. This new program seeks to leverage innovative technologies such as tissue and bio- engineering, biomaterials and scaffolds, iPS technology, cell directed therapy, and humanized animal models that are not used widely in lung regeneration research, but are being applied to investigate regeneration and repair in organ systems outside of the lung, and incorporate these novel methods to further knowledge of lung repair and regeneration. The program also seeks to build on knowledge gained from research in molecular embryology and developmental biology of the lung, acute and chronic lung injury, pathobiology of lung diseases including pulmonary fibrosis, and research on lung progenitor cell biology and to bring together the investigators, ideas, and tools from each of these research domains as well as regenerative science experts of other organs and bioengineers, to create partnerships that will be needed to forge new research directions and identify strategies to induce functional lung tissue regeneration of lung cell compartments.

The lung is normally not a highly proliferative tissue, but proliferation does occur following injury. Recent evidence suggests that there may not be true lung stem cells, but rather multipotent or lineage-committed cell populations (either progenitor or fully differentiated) that respond after significant injury in order to repopulate the epithelium with a myriad of cell types needed for functional recovery. Controversy exists however as to the differentiative repertoire (pluripotent, multipotent, or unipotent) of progenitor cells within the lung and whether these properties are possessed by a privileged few stem/progenitors cells or by a broad variety of many lung cells. Moreover, the reparative/regenerative mechanisms controlling the cell fate decisions, self-renewal decisions, or capacity for transdifferentiation (cell plasticity) of the cells in question remains unknown, in part because tools and models needed to explore the biology of lung repair/regeneration in specific cell subsets are lacking or insufficient. 

Research proposed for this FOA may utilize any compartment(s) of the respiratory system including epithelium, mesenchyme, and/or endothelium from the upper airway to alveolus and must have clear relevance to human health and disease. The goal is to address an important gap in knowledge in the lung field that would lead to development of new regenerative medicine strategies for reversing debilitating and life limiting disorders such as acute lung and/or tracheal injury, bronchopulmonary dysplasia, cystic fibrosis, pulmonary fibrosis, and COPD.

Known lung cell markers are insufficient for lung progenitor cell identification, isolation, and lineage tracing of >40 cell types in the lung. In addition, efforts to translate findings in preclinical models to human have highlighted the need for better models to reflect human disease.  Novel tools/reagents that would accelerate reaching the goal of improved understanding of human lung repair/regeneration may include for example, tools/reagents that would facilitate lung stem/progenitor cell identification, isolation, lineage tracing, and in vivo imaging; new technology that can support regeneration of lung tissue (such as gradients of growth/paracrine factors that can differentiate/ dedifferentiate lung cells); and new in vivo and in vitro injury models to elucidate regenerative potential in  human acute and chronic lung diseases.

Each application must include experts from two or more disciplines working together to address mechanisms of lung repair/regeneration.  Scientific expertise may include: developmental/stem/progenitor cell biology, lung injury, pulmonary medicine, physiology, genomics, tissue or bio-engineers, nanotechnology, and integrative, systems approaches.  Participation of experts in stem cell biology and tissue regeneration of non-lung organs and bioengineering is strongly encouraged.  Collaboration among research centers in both hypothesis-driven research and rapid sharing of models/reagents developed in the Consortium will be expected.

Program Structure

The goal of this FOA is to develop a highly interactive and synergistic Consortium of investigators who will share ideas, data, and resources to move the field of lung regeneration forward. The Consortium will consist of up to six Research Center projects funded through this FOA, and an Administrative Coordinating Center (ACC) supporting the Consortium funded through a separate FOA, RFA-HL-12-010 http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-010.html. The ACC will also administer funds available in years 2-5 to support collaborative studies and resource validation studies across participating sites in the Consortium and a Skills Development Core in tissue regeneration.  Collaboration and interaction among LRRC investigators will be a requirement of the program and will be facilitated with a website, teleconferences, and biannual meetings of the investigators organized by an Administrative Coordinating Core (ACC).

Collaborative Research Studies: A major goal of the Lung Repair and Regeneration Consortium is to foster highly innovative, high-risk approaches that are not easily funded by traditional mechanisms and that have the potential for unusually high impact that could significantly advance the field. Solicitations for collaborative studies across two or more Consortium Research Centers will be initiated beginning in Year 1 by the ACC with project support for 1-3 years with approximately $100,000-$150,000 direct costs per year starting in year 2. The studies are also expected to be helpful in developing young investigators and may bring in outside experts. The External Advisory Committee will be responsible for peer review of these new collaborative studies. Progress on these studies will be monitored by NHLBI program staff.

Collaborative Resource Validation Studies:  As new resources such as reagents, models, and tools are developed by individual Research Centers, confirmation of the application of these will be fostered through solicitations for resource validation by other Research Centers in the Consortium.  Beginning in Year 2, solicitations for resource validation studies will be issued by the ACC at direct costs of approximately $50,000-$150,000 for one year. The External Advisory Committee will be responsible for peer review of these new validation studies. Progress on these studies will be monitored by NHLBI program staff.

Skills Development Core: Each Research Center will be responsible for participation in a Skills Development Core, coordinated by the ACC, that helps young investigators develop skills and experience to progress to more senior status in the field of lung regenerative medicine.  The Skills Development Core will support travel and costs for supplies and equipment to support developmental activities, courses, seminars, workshops, and other activities directly related to the development plan for junior investigators across the Consortium.  A Skills Development Committee, composed of an investigator from each Research Center and from the ACC, will develop and coordinate activities among the Research Centers to enhance skills development for graduate students, postdoctoral fellows, and young faculty. Each application should identify a Skills Development Coordinator, whose relevant experience is well documented in the Research Plan. The budget must include support for a minimum of 2.4 calendar months effort for the applicant PI or a minimum of 2.4 calendar months combined effort for all PIs if the multiple PI strategy is used.  The budget should identify an individual with experience in skills development who will serve as representative on the Skills Development Committee.  This individual should declare a minimum effort of 0.6 calendar months specifically for skills development activities, in addition to any research activities undertaken by the individual.

A three page Skills Development Plan should include a concept proposal for components of a skills development core that the research center could offer, including skills for collaborating with clinicians and conducting human tissue research.  Skills development activities and budgets will be developed across the Consortium after funding.

Steering Committee: The LRRC will have a Steering Committee that will be responsible for overall scientific direction, coordination, and oversight. The Steering Committee will be composed of the Lead PI/PDs for each Research Center, the ACC PI/PD, and the NHLBI Project Scientist. The Steering Committee will be chaired by an investigator selected by the NHLBI. The Steering Committee will meet in person for an implementation meeting at the start of the project period, by conference call at least quarterly, and in person at least twice a year throughout the project period (one of these meetings at the Annual Grantee Meeting—see below). Participation in Steering Committee activities is a requirement of at least one PI/PD from each Research Center. Funds should be requested to attend Steering Committee meetings as well as other collaborative meetings of the LRRC.

External Advisory Committee: An External Advisory Committee (EAC) will oversee the Consortium. The Committee will consist of non-Consortium affiliated scientists and other experts appointed by the NHLBI to provide annual reviews of progress, and serve as the peer review panel for collaborative studies.

Annual Grantee Meeting: The ACC will arrange annual meetings to encourage the exchange of information for the LRRC. In the preparation of the budget for the grant application, applicants should include travel funds for one meeting each year to be held in or near Bethesda, MD, for the Principal Investigators, key collaborators, and trainees. A major goal of these meetings is to facilitate progress by providing a forum that will lead to sharing skills, ideas, technology, data, and biological reagents.  At the meetings, participants will discuss quality assurance, bioinformatics, coordination, sharing, and a means of informing the community about progress made by the Consortium.

Administrative Coordinating Core (ACC): see http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-12-010.html for more details The ACC will serve a range of functions such as organizing meetings; arranging teleconference calls of the Steering Committee, External Advisory Committee, and Consortium annual meeting; and designing and maintaining written materials and websites to support the Consortium. The ACC will be responsible for solicitation of applications for collaborative pilot studies and tool validation studies. The ACC will oversee the review and award of collaborative funds for the Consortium, award subcontracts for these funds, assist in the Skills Development Core, and coordinate the submission of progress reports by the awardees for review by the External Advisory Committee and NHLBI staff.

During the course of the funding period, technologies will improve and the rate of progress and scope of the research may change.  It is expected that the Principal Investigators, in consultation with NHLBI program staff, will make necessary adjustments to accommodate the changing research environment, to remain focused on appropriate goals, and to maintain excellent coordination with the other projects funded under this RFA.

Data and Reagent Sharing: All applications submitted through this announcement and the companion FOA (RFA-HL-12-010) must include technology transfer and sharing plans for both data and unique research resources that are generated by the projects in concordance with NHLBI/LRRC policies. It is expected that resources developed by the LRRC will be made available to the broader scientific community, after a propriety period, at no charge other than the cost of reproduction and distribution. Applicants must indicate their willingness to distribute research tools to the wider community including antibodies, transgenic mouse strains, microarray data, and other reagents.  A distribution plan should be included in the application.  Likewise, applicants must describe their willingness to submit microarray data generated through this project and other pertinent information about research resources generated through this U01 to the LRRC Coordinating Center as the resources are developed.

Selected Research Examples include but are not limited to:

1.         Use novel lung repopulation models and humanized animal models that allow functional assessment of how putative progenitor or other cells respond to promote repair and regeneration. Studies based solely on immunostaining of banked tissue sections for human studies would not be acceptable under this FOA.

2.         Initiate new collaborations with tissue and bio-engineers to investigate use of novel scaffolds and biomaterials to study mechanisms of lung repair and regeneration. Utilize tissue engineering strategies to modify the endogenous lung microenvironment to identify local determinants and regulators of lung regeneration.

3.         Apply induced pluripotent stem cell research or cell directed therapies using putative progenitor cell populations to deliver transcription factors or other molecules of interest in order to elucidate mechanisms of lung repair/regeneration.

4.         Elucidate the influence of the microenvironment on progenitor cell self-renewal and differentiation.

5.         Investigate the use of novel transcription factors for cell expansion and differentiation.  Investigate mechanisms controlling cell fate decisions and self-renewal after injury and the potential for cell plasticity of resident lung cells.

6.         Identify molecules and pathways signaling adaptive and maladaptive responses after injury in animal models and validate findings of key signaling pathways involved in human lung regeneration.

7.         Determine developmentally dependent changes in histone methylation, histone acetylation and DNA methylation, during reparative responses to injury.

Selected Tool Development examples include but are not limited to:

1.         Develop models to lineage trace individual cell types in the epithelium, endothelium, and/or mesenchyme that contribute to lung repair/regeneration.

2.         Develop nanoscale and microscopy methods to study progenitor cell markers on lung epithelial, endothelial, mesenchymal compartments.

3.         Develop genetic cell marking technology for lung epithelial cell lineages over the course of development, structural growth, repair and regeneration.

4.         Develop tools to identify subphenotypes of lung cells based on molecular signatures during maintenance and repair after injury.

5.         Develop novel functional assays of “stemness” for lung.

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.   

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards


NHLBI/DLD intends to commit $4 million and 6 awards in FY 2012.

Award Budget

Application budgets are not limited, but need to reflect actual needs of the proposed project.

Award Project Period

 5 Years  

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.

Section III. Eligibility Information

1. Eligible Applicants
 
Eligible Organizations

Higher Education Institutions:

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

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

Foreign (non-U.S.) components of U.S. Organizations are  allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Project Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) 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 PHS398 Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Section IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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 research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: 301-435-0270
Fax: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the appendix files must be sent to:

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: 301-435-0270
Fax: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Page Limitations
 
Research Plan

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Research Skills Development Plan:

A three page Skills Development Plan is to be included following the 12 page Research Strategy. The Skills Development Plan must include a concept proposal for components of a skills development core that the research center could offer, including trainee recruitment, skills for collaborating with clinicians and conducting human tissue research, and career development. Each application should identify a Skills Development Coordinator, whose relevant training experience is documented in the Skills Development Plan.

Resource Sharing Plans

Individuals are required to comply with instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) Sharing Plan) as provided in the PHS 398 Application Guide)

For this FOA, investigators are expected to include a description of how resources generated will be shared with other members of the Consortium, and rapidly made available to the scientific community.  Resources may include new reagents, lineage tracing technologies, image analysis, or data analysis tools..

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.  

Foreign Organizations

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the PHS398 Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will be returned to the applicant without review.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NHLBI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

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.

Overall Impact - Overall

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

Scored Review Criteria - Overall

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

Significance

Does the 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?  What is the quality of the potential benefit and acceleration of the field of lung repair/regeneration?  What is the potential of these projects to accelerate lung research?  

Investigator(s)

Are the PD/PIs, 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?  Do the investigators have documented experience with coordinating basic and translational research, particularly in the areas related to organ repair/regeneration?  Do(es) the PI(s) have prior experience with collaborative research?  Are new multidisciplinary teams organized to address novel questions relevant to lung repair and regeneration?  What is the likelihood that these projects can be accomplished by these investigators?      

Innovation

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?  Will the investigators bring expertise that can develop models/tools/reagents/technologies that are novel and innovative?

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? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?    

Will the project proposed benefit from collaborative interactions with the consortium?  Will the proposal allow flexibility in collaboration with the consortium?  Will the investigators bring valuable areas of expertise to the consortium that will maximize flexibility for the program?  Does the application describe prior successful collaborative research? 

Environment

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 - Overall

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/priority 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not Allowed

Renewals

Not Allowed

Revisions

Not allowed

Additional Review Considerations - Overall

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/priority score.

  Data generation and dissemination plan:  How will the anticipated data benefit the scientific community?  How will data handling and analysis benefit from collaboration with the consortium? Will the data be interoperable with existing resources?  Will the data collection follow accepted standards? Does the dissemination plan propose rapid dissemination of data and resources without restrictions in regard to prior publication by consortium members?

Skills Development Core: The reasonableness of the proposed Research Skills Development Core and estimated level of funding will be evaluated as either acceptable or unacceptable. The Skills Development Core will be evaluated for its effectiveness in developing the skills and research capabilities of new investigators. This will include an evaluation of:

1.  Senior Investigators: Does the applicant provide evidence of appropriate credentials and success records of the Principal Investigator, Core Project Leader, and other participating senior investigators as researchers and trainers?

2.  Recruitment: Is the quality of the methods by which trainees are to be recruited and selected, including the plans to recruit women and minority individuals appropriate to the aims of the proposed studies? Are high quality trainees available to participate in the proposed research?

3.  Development Plan: Are the plans provided for developing the skills of trainees; are the types of skill and technologic development proposed of appropriate quality to promote progression to more independent researcher status?  Is there evidence of sufficient and clearly defined mentoring activities?  Are proposed training activities well coordinated with participating senior investigators?  Will steps be taken to avoid overlap or duplication with existing training opportunities at the applicant institution?  Is there evidence of a distinct training opportunity to offer LRRC as a collaborative training project?

4.  Impact: Is the quality of the plan for measuring the effectiveness of the training program, including progression to more independent status appropriate for the proposed program?

Applications from Foreign Organizations

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.

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

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.

2. Review and Selection Process

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

As part of the scientific peer review, all applications will:

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 NHLBI Advisory Council . The following will be considered in making funding decisions:

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) via the eRA Commons

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

Section VI. Award Administration Information

1. Award Notices

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 business official.

Awarde0es 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.      

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.

Awardee(s) agree to the governance of the study through a Steering Committee. Steering Committee voting membership shall consist of the principal investigators (i.e., cooperative agreement awardees), the NHLBI Project Scientist, and the Chairperson, and the ACC PI.  Meetings of the Steering Committee will ordinarily be held by telephone conference call or in the metropolitan Washington Area.

Study investigators are encouraged to publish and to release publicly and disseminate results and other products of the study, in accordance with study protocols and governance. Within three years of the end of the period of NHLBI support for the project, data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators, provided such release is consistent with the study protocol and governance.  In addition, study investigators must establish a plan for making data sets and materials available to the scientific community and to the NHLBI immediately upon completion of the three year period following the end of the period of NHLBI support.

Upon completion of the project, awardees are expected to put their intervention materials and procedure manuals into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community and the NHLBI, for the conduct of research at no charge other than the costs of reproduction and distribution.

The collaborative protocol and governance policies will call for the continued submission of data centrally to the coordinating center for a collaborative database; the submittal of copies of the collaborative datasets to each principal investigator upon completion of the study; procedures for data analysis, reporting and publication; and procedures to protect and ensure the privacy of medical and genetic data and records of individuals. The NHLBI Project Scientist, on behalf of the NHLBI, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.

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.

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

The NHLBI Project Scientist will serve on the Steering Committee; he/she or other NHLBI scientists may serve on other study committees, when appropriate. The NHLBI Project Scientist (and other NHLBI scientists) may work with awardees on issues coming before the Steering Committee and, as appropriate, other committees, e.g., data sharing and database development, quality control, adherence to protocol, core establishment.

The NHLBI reserves the right to withhold funding or curtail the study (or an individual award) in the event of (a) substantive changes in the agreed-upon work scope with which NHLBI cannot concur, (b) human subject ethical issues that may dictate a premature termination.

Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NHLBI support; or special access to study results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

Additionally, an agency program official or NIH program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.  The assigned program director may also serve as an NIH Project Scientist.

Areas of Joint Responsibility include:

Awardees agree to the governance of the Consortium through the Steering Committee.  Membership will include, at a minimum, the Consortium PIs, the PI of the ACC, and the NHLBI Project Scientist.  The Steering Committee Chair will be appointed by NHLBI.  Additional members may be added by majority vote of the Steering Committee.

Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee, and recommendations from the External Advisory Committee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: 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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

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

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Carol J. Blaisdell, M.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10042
Bethesda, MD 20892-7952
Bethesda, MD 20817  (express/courier service  )
Telephone: 301-435-0222
Email:blaisdellcj@nhlbi.nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone:  301-435-0270
Fax:  301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

David Duane
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7134
Bethesda, MD 20892-7926
Bethesda, MD 20817 (express/courier zip service)
Telephone: 301-435-0166
Fax: 301-451-5462
Email:ruaned.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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 Parts 74 and 92.


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