and Human Services (HHS)
EXPIRED
Participating Organization(s) |
National Institutes of Health (NIH) |
National Heart, Lung, and Blood Institute (NHLBI) |
|
Funding Opportunity Title |
Toward An Improved Understanding of HDL Function, NHLBI (R01) |
Activity Code |
R01 |
Announcement Type |
New |
Related Notices |
|
Funding Opportunity Announcement (FOA) Number |
PA-11-012 |
Companion FOA |
|
Catalog of Federal Domestics Assistance (CFDA) Number(s) |
93.837 |
FOA Purpose |
This FOA encourages grant applications that propose to develop, validate, and standardize assays to measure HDL function and biomarkers for HDL function and to identify novel genes, pathways, and potential HDL targets in the relationship to HDL function. Innovative methods to determine HDL functional properties such as in vivo reverse cholesterol transport (RCT), anti-oxidant, anti-inflammatory, and antithrombotic activities, and biomarkers for HDL function are encouraged. Projects that will explore HDL functional pathways, new genes and therapeutics related to HDL function are also encouraged. |
Posted Date |
October 25, 2010 |
Open Date (Earliest Submission Date) |
January 6, 2011 |
Letter of Intent Due Date |
Not Applicable |
Application Due Date(s) |
February 5, 2011, by 5:00 PM local time of applicant organization. |
AIDS Application Due Date(s) |
May 7, 2011 |
Scientific Merit Review |
June/July 2011 |
Advisory Council Review |
October 2011 |
Earliest Start Date(s) |
December 2011 |
Expiration Date |
May 8, 2011 |
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.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission
Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
The purpose of this Funding Opportunity Announcement (FOA) is to develop, validate, and standardize assays to measure HDL function and biomarkers for HDL function and to identify novel genes, pathways, and potential therapeutic targets in relation to HDL function.
Background
Epidemiological studies demonstrating a strong association of lipid levels with atherothrombotic events suggest the therapeutic potential of lipid-targeted therapy. The benefit of lowering LDL is well demonstrated in many randomized trials. Current understanding suggests that therapeutic manipulation of HDL should also be useful in reducing cardiovascular risk. For instance, animals infused with HDL particles and transgenic mice overexpressing the major HDL apolipoprotein, apoA-I, have shown a marked reduction in atherosclerosis. In addition, small studies in humans using coronary intravascular ultrasound (IVUS) suggest that infusion of reconstituted HDL particles is associated with regression of atherosclerosis. However, despite substantial experimental support, there are as yet no randomized trials demonstrating a benefit of HDL-targeted therapy. In fact, the failure of torcetrapib (an inhibitor of cholesterol ester transfer protein (CETP)) to be beneficial, despite raising HDL levels, has generated concern about HDL therapy more generally. This failure underscores the incompleteness of our fundamental understanding of HDL function rather than a lack of therapeutic potential of HDL manipulation.
In addition, genetic and other studies in humans indicate the complexity in the relationship of HDL to atherosclerosis. Naturally occurring genetic conditions in humans indicate that lower HDL-C values are not uniformly associated with excess cardiovascular risk. Also, higher HDL-C levels may not always confer a protective benefit. These data emphasize the importance of HDL function.
HDL particles are heterogeneous in shape, density, size, composition and have multiple functional properties such as reverse cholesterol transport (RCT), as well as anti-oxidant, anti-inflammatory, and antithrombotic activities. Promotion of cholesterol efflux from macrophages, its return to the liver and ultimately biliary excretion, completing the pathway of RCT, is thought to be one of the most important mechanisms by which HDL protects against atherosclerosis. Recent research highlights other functional properties of HDL as mentioned above as well.
Currently, there are no standard methods to assess HDL function in humans. Macrophage-specific assays have been useful in mice; however, their applicability to humans remains uncertain. Developing robust, reliable, and reproducible assays to assess HDL function in humans will allow early assessment of changes in HDL functionality in response to new HDL-targeted therapies. Assays for other HDL functional properties such as anti-oxidant and anti-inflammatory effects are needed as well. There is a major need to study HDL and its role in atherogenesis, especially in developing and validating HDL functional assays and elucidating mechanisms of HDL function from recent studies such as information from genome-wide association studies (GWAS) by multidisciplinary and collaborative research.
Objectives
The ultimate goal of this FOA is to develop reproducible and robust assays to measure HDL function and to identify novel genes and pathways related to HDL function.
To address this goal, research projects prompted by this FOA are expected to advance such areas as:
To maximize the likelihood of success, projects that bring together experts in multidisciplinary fields such as clinical chemists, biochemists, cell and molecular biologists, geneticists, physiologists, and clinicians are encouraged. Projects leveraging NHLBI and industry randomized trials, with their large, well-characterized patient populations, are encouraged as well.
Funding Instrument |
Grant |
Application Types Allowed |
New |
Funds Available and Anticipated Number of Awards |
The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications. |
Award Budget |
Application budgets are not limited, but need to reflect actual needs of proposed project. |
Award Project Period |
The scope of the proposed project should determine the project period up to a maximum of five 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.
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.
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.
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 SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.
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.
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 provided at Grants.gov.
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.
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 application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.
All instructions in the SF424 (R&R) Application Guide must be followed.
Resource Sharing Plans
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) Sharing Plan) as provided in the SF424 (R&R) Application Guide.
Appendix
Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.
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.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Meritorious applications within the scope of this FOA will have high program relevance for NHLBI funding consideration. Any pay line advantage will not be applied to resubmissions and renewals. Resubmission, renewal, or revision applications should be submitted using another FOA for R01 applications that permits resubmission, renewal, or revision applications (e.g. PA10-067)
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.
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.
Applicants are required to follow the instructions for post-submission materials, as described in
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).
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?
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?
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?
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 Applicable.
Renewals
Not Applicable.
Revisions
Not Applicable.
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 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.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) (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 be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of review by the NHLBI Advisory Council. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.
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.
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.
We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.
Grants.gov
Customer Support (Questions regarding Grants.gov registration and
submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: [email protected]
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]
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: [email protected]
Lijuan Liu, Ph.D.
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 8156, MSC 7956
Bethesda, MD 20892-7956
Telephone: (301)-435-0550
FAX: (301)-480-3667
Email: [email protected]
Michael J Domanski, M.D.
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 8146, MSC 7956
Bethesda, MD 20892-7956
Telephone: (301)-435-0550
FAX: (301)-480-3667
Email: [email protected]
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
Anthony J Agresti
Office of Grants Management
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7158, MSC 7926
Bethesda, MD 20892-7926
Telephone: (301)-435-0186
FAX: (301)-480-3310
Email: [email protected]
Teresa F Marquette
Office of Grants Management
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7128, MSC 7926
Bethesda, MD 20892-7926
Telephone: (301)-435-0166
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
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NIH Funding Opportunities and Notices
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