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

Discovery of Genetic Basis of Mendelian or Monogenic Heart, Lung, and Blood Disorders (X01)

Activity Code

X01 Resource Access Award

Announcement Type

New

Related Notices

  • May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

Funding Opportunity Announcement (FOA) Number

PAR-11-307

Companion FOA

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

 93.838, 93.233, 93.837, 93.839

FOA Purpose

The National Heart, Lung, and Blood Institute (NHLBI) invites applications to use the exome sequencing capacity of the Mendelian Disorders Genome Centers to carry out studies to investigate the genetic basis of Mendelian or monogenic disorders that significantly affect heart, lung, and blood (HLB) systems.

Key Dates
Posted Date

August 12, 2011

Open Date (Earliest Submission Date)

September 18, 2011

Letter of Intent Due Date

September 19, 2011; April 16, 2012; April 15, 2013; and April 14, 2014

Application Due Date(s)

October 18, 2011; May 14, 2012; May 14, 2013; and May 14, 2014 , by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

March 2012; October 2012; October 2013; and October 2014

Advisory Council Review

May 2012; January 2013; January 2014; and January 2015

Earliest Start Date(s)

July 2012; April 2013; April 2014; and April 2015

Expiration Date

May 15, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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.


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Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

To stimulate discoveries of the genetic basis of Mendelian or monogenic disorders that significantly affect heart, lung, and blood (HLB) systems, the NHLBI invites X01 to use the genome-wide sequencing capacity of the Mendelian Disorders Genome Centers which are funded under the HG-10-016.

Nature of the research opportunity

The studies supported by this FOA must have existing genomic DNA samples collected from patients with suspected Mendelian or monogenic disorders and must use the exome sequencing capacity of the NHGRI-funded Mendelian Disorders Genome Centers for the discovery of causal genetic variants.  No funds will be provided to collect samples.  Applications must focus on heart, lung, blood, and sleep (HLBS) disorders influenced largely by genetic variant(s) in a single gene.

Background

It is estimated that about 25 million Americans have one of the 7,000 rare diseases.  The vast majority of these disorders are genetically determined and very likely caused by genetic mutation(s) in a single gene.  In the Online Mendelian Inheritance in Man (OMIM) database, there are more than 400 suspected Mendelian diseases related to heart, lung, blood, and sleep whose genetic basis is still unknown.  

These Mendelian diseases will not only provide the rare windows of opportunity to observe how nature works, but also may reveal the biological basis of related common diseases.  Familial hypercholesterolemia (FH) is an excellent example.  Exome sequencing technology has proven to be an efficient and cost-effective way to identify causative mutations in monogenic diseases.

Types of Research Projects

This FOA seeks projects that show promise for identification of causal genetic variants using exome-sequencing technology.  There should be evidence that the project proposed is likely to have the power to detect genetic mutations affecting the Mendelian trait under study.  Besides obvious Mendelian traits, the FOA also provides an opportunity to discover de novo mutations and identify the causes of some hard-to-diagnose rare diseases. 

For suspected Mendelian disorders, applicants are strongly encouraged to address as many of the following  points as possible.  Applicants who work on monogenic but not typical Mendelian disorders should also try to respond to all relevant points.

Applicants are encouraged to propose phased projects, starting with the minimum number of probands needed for initial discovery.  After approval to access the exome-sequencing capacity, X01 applicants will work with NHLBI, NHGRI, and the sequencing centers to determine the timing and number of DNA samples to be sequenced.  The relationship between the X01 investigators and the Mendelian Centers investigators should be collaborative in nature.  The details of the collaboration should be worked out between the investigators up front.  NHLBI and NHGRI will facilitate communications among the investigators where necessary. 

Section II. Award Information
Funding Instrument

This is an access award, not a grant.

Application Types Allowed

New
Resubmission

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

Contingent upon the receipt of a sufficient number of meritorious applications, NHLBI intends to approve 15 (X01) projects each year between 2012 and 2014.

Award Budget
Award Project Period

 Maximum period 4 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 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 apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) 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 (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program 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 SF 424 (R&R) 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. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.  

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this 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 the SF424 (R&R) 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.

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

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:

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities  
National Heart, Lung and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following requirement:

R&R or Modular Budget Component

This X01 does not award grant funds; therefore no budget information should be provided.

PHS 398 Research Plan Component

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

Resource 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:

Appendix

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

Foreign Institutions

Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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 (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.

 However, X01 proposals should not include any budget information as no funds will be provided. 

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide.  Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). 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 by the Center for Scientific Review NIH.  Applications that are incomplete  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

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

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?  Is the trait under study significant to human health and/or the understanding of biology? Is there strong evidence for a genetic component and documentation of the anticipated size of the genetic effect? Are the proposed studies likely to provide important new information about genetic variants important in human health or disease?     

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?   

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?   

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?  Are the sequencing services requested appropriate for the question addressed? Are the specific phenotypic measures appropriately chosen and carefully determined? Is the study design appropriate for the trait under study?  Does the sample set have the power to detect the likely genetic effect? 
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?  

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

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

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

Renewals

Not Applicable

Revisions

Not Applicable.

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/priority score.

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 sequencing data sharing plans or the rationale for not sharing are reasonable.  Applicants are expected to share their data under the guidance of NIH Genome Wide Association Studies (GWAS) policy.

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 convened by the NHLBI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available resources 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 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 award, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement and http://grants.nih.gov/grants/policy/hs/hs_policies.htm . As this is an X01 and no funds are attached, an NoA will NOT be generated by NHLBI.

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

Not Applicable

3. Reporting

Not Applicable.

Section VII. Agency Contacts

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

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

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)

Weiniu Gan, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Suite 10164, MSC 7952
Bethesda, Maryland 20892-7952
Telephone:  (301) 435-0202
Email:  ganw2@nhlbi.nih.gov

Pankaj Qasba, Ph.D.
Program Director, Blood Diseases Branch
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, MSC 7950
Bethesda, MD 20892-7950
Telephone:  301-435-0050 
Fax:  301-480-0867 
E-mail: qasbap@nhlbi.nih.gov

Deborah Applebaum-Bowden, Ph.D.
Division of Cardiovascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Dr, MSC 7940
Bethesda, MD 20892-7940
Telephone: (301) 435-0513
FAX: (301) 480-1454
Email: applebad@nhlbi.nih.gov

Cashell E. Jaquish, Ph.D.
Division of Cardiovascular Sciences   
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Suite 10018, MSC 7936
Bethesda, MD 20892-7934
Telephone: (301) 435-0447
FAX: (301) 480-1455
Email: jaquishc@nhlbi.nih.gov

Dina N. Paltoo, Ph.D., M.P.H.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 9180
Bethesda, MD 20892
Telephone: (301) 435-0513
FAX: (301) 480-1336
Email: paltood@mail.nih.gov

Charlene Schramm, PhD
Deputy Branch Chief, Heart Development and Structural Disease Branch
Division of Cardiovascular Diseases
National Heart, Lung, and Blood Institute
National Institutes of Health, DHHS
6701 Rockledge Dr., Rm. 8100, MSC 7940
Bethesda, MD 20892-7940 (Use zip code 20817 for courier delivery)
phone: (301) 435-0510
fax: (301) 480-2858
email: schrammc@nhlbi.nih.gov

Peer Review Contact(s)

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
National Institutes of Health
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
Telephone: 301-435-0270
Fax: 301-480-0730
Email: nhlbichiefreviewbranch@nhlbi.nih.gov

Financial/Grants Management Contact(s)

Not Applicable.

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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