Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations     
National Heart, Lung, Blood Institute, (http://www.nhlbi.nih.gov)
National Human Genome Research Institute (NHGRI) (http://www.nhgri.nih.gov)

Title:  Development and Application of New Technologies to Targeted Genome-wide Resequencing in Well-Phenotyped Populations (R01)

Announcement Type
New

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Request for Applications (RFA) Number: RFA-HL-08-004

Catalog of Federal Domestic Assistance Number(s)
93.837, 93.838, 93.839, 93.233, 93.172   

Key Dates
Release/Posted Date:
Opening Date:  January 28, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): January 28, 2008
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization). 
Application Submission/Receipt Date(s):  February 28, 2008
AIDS Application Submission/Receipt Date(s):  Not applicable
Peer Review Date(s): May-June 2008 
Council Review Date(s): August 2008
Earliest Anticipated Start Date(s): September 30, 2008
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: February 29, 2008

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives


Section II. Award Information

1. Mechanism of Support

2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants

    A. Eligible Institutions
    B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information

2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Submission, Review, and Anticipated Start Dates
          1. Letter of Intent
    B. Submitting an Application Electronically to the NIH
    C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices

2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)

2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Purpose

The National Heart, Lung, and Blood Institute (NHLBI) and National Human Genome Research Institute (NHGRI) solicit grant applications under this Funding Opportunity Announcement (FOA) to develop and validate a resequencing application for cost-effective, high-throughput sequencing of genome-wide medical targets by assembling current and emerging technologies in the areas of DNA target capture and sequencing.  The sequencing targets are primarily all exons of the 20,000 protein coding genes identified as RefSeq genes in Entrez Gene database at the National Center for Biotechnology Information (NCBI), which account for 1-2% of the human genome, but could include other types of functional units such as microRNA and regulatory elements.  The purpose of developing this resequencing application is to enable the sequencing of thousands of individual DNA samples in NHLBI’s well-phenotyped populations in a cost-effective manner.  Applicants must therefore demonstrate the potential to reduce costs towards this goal, while providing data of sufficient quality for distinguishing sequence variants.

Background

The NHLBI intends to create a public resource that will host individual sequencing information along with phenotype data of thousands of selected individuals from its well-phenotyped populations.  If the resequencing pipeline developed under this FOA is proven feasible for being applied to large populations, NHLBI will consider releasing a subsequent FOA to support the resequencing of thousands of DNA samples in its well-phenotyped populations that have adequate consents for data sharing.      

The NHLBI provides leadership for a national research program in heart, lung, and blood diseases, and sleep disorders.  Three of the top four leading causes of deaths in the US are heart and lung diseases.  In 2004, cardiovascular, lung, and blood diseases accounted for 1,099,000 deaths (Estimated based on Vital Statistics of the United States, NCHS) and 46 percent of all deaths in the United States.  The projected economic cost in 2007 for heart, lung, and blood diseases is expected to be $599 billion, 23 percent of the total economic costs of illness, injuries, and death.  Most of these diseases are common chronic diseases that are inherited as complex traits. 

To battle these diseases more effectively, NHLBI has just launched a new strategic plan for the next five to ten years (http://apps.nhlbi.nih.gov/strategicplan/Default.aspx), and one of the fundamental strategic goals is to elucidate the genetic architecture of relevant diseases.  The most efficient and cost-effective way to achieve this goal is to create publicly available databases in which common as well as rare genomic variants are associated with all available clinical phenotypes for thousands of individuals in NHLBI’s population-based and outcomes research.  This effort requires a cost-effective and high-throughput resequencing application that will be developed under this FOA. 

The genetic factors that contribute to complex traits of many heart, lung and blood diseases are multi-factorial and probably composed of both common genomic variants (≥5%), which have small effects, and rare sequence variants (≤5%), which have large effects.  The development of high-throughput genotyping technologies has permitted Genome-wide Association Study (GWAS) of common variants associated with complex traits.  The effort to systematically screen for common genomic variants is well under way through NHLBI-funded GWAS programs.  A growing number of papers published within the last two years substantiate the overall validity of the GWAS approach.  However, this work also has highlighted several limitations of GWAS, including the inability to discover unknown genetic variants and detect rare variants associated with complex diseases, and difficulties in validating the biological function of the variants found outside known gene boundaries. 

The recent success from an association study of rare variants and quantitative traits using deep population resequencing of the target gene (Cohen and colleagues, 2007) prompted the call for developing methodologies for systematic ‘deep’ resequencing in large populations (Topol & Frazer, 2007).  Systematic screening of rare variants located within functional units in the human genome would overcome shortcomings of GWAS and permit investigation of the large effects of rare variants within biological networks.  The combination of each individual’s genomic rare variants and common variants for thousands of individuals in NHLBI’s large, well-phenotyped populations would provide an unprecedented opportunity to realize the capacity of human genetics to yield major new insights into disease mechanisms, including those attributable to low penetrance genetic lesions accounting for a small amount of phenotypic variance. 

Sequencing is the technology that can discover common and rare genomic variants, including the common type of variant bi-allelic single nucleotide polymorphisms (SNP) and relatively uncommon types tri-allelic SNP and indels (i.e. insertions or deletions in the genome).  Whole genome resequencing would be an ideal approach, if it is not too costly to be applied to large populations.  Currently, the most feasible approach is to resequence genome-wide medical targets, such as every exon [i.e. exome] of all 20,000 human RefSeq genes (accession number starting with NM_).  The exome accounts for 1-2% of the whole genome and could be sequenced for a fraction of the cost of the whole-genome.  More importantly, this approach could identify nearly all genomic variants that are localized with all selected functional regions of the genome.  Results obtained with this strategy will provide new hypotheses for the involvement of specific genes and their products in disease etiology.  As it is extremely difficult to elucidate the molecular function or impact of any variant that is not located within a known functional feature, the exome approach will remain practical strategy even when large-scale whole-genome sequencing approach is feasible. 

There are many areas of high priority research to which resequencing genome-wide medical targets at dramatically reduced cost would make vital contributions. 

The systematic screening for synonymous and nonsynonymous variants in the various populations focused on cardiovascular diseases will provide the biomedical research community an unprecedented opportunity to identify the genes that may have impact on the development of complex traits in cardiovascular diseases.

Delineating genetic architecture of asthma by integrating data from the genetics studies of the last 15 years, including linkage studies, genome-wide association studies, and exome resequencing.

Creation of a publicly available COPD (Chronic Obstructive Pulmonary Disease) genetics database including a comprehensive catalogue of common and rare genomic variants and phenotypes from COPD genetics studies. 

Study of synonymous and nonsynonymous variants in sickle cell patient populations could lead to the identification of a list of modifier genes that may impact the severity of the disease.

The genomic variants discovered by the exome project of in a multi-ethnic population will create a database containing comprehensive catalogue of synonymous and nonsynonymous variants within African American and Asian populations and provide the much-needed data for studying genetic risk factors that are specifically associated with African American populations. 

The development of sequencing technology has been on a fast-track to increase accuracy and reduce costs.  The cost reduction for sequencing (de novo) a mammalian-sized genome (approximately 3 gigabases [Gb]) has been accelerating in recent years from hundreds of millions in the late 1990s to $5-10 million currently.  The current state-of-the-art sequencing technology - the chain terminator sequencing (Sanger sequencing) resolved by capillary electrophoresis (CE) - has been challenged recently by new technologies (‘next generation’ sequencing technologies) that are described as massively parallel single-molecule DNA sequencing technology.  They can produce up to millions of short sequencing reads (30 bp to 200 bp) in a single run and detect the sequence at the single DNA molecule level.  The three current next-generation sequencing technologies detect DNA sequence, respectively, by pyrosequencing technology, reversible terminator technology, and sequencing by ligation technology.  These next generation sequencing technologies soon will be able to reduce the cost of sequencing (de novo) a mammalian-sized genome to $100,000 and make the $1,000 per individual exome (1-2% of the genome) a reachable goal in the near future.   

Technology Components

In order to demonstrate the promise of genome-wide targeted resequencing approaches, applications should address all critical elements of a resequencing pipeline.  This FOA is intended to stimulate advances in all critical elements, including:

Sample preparation. Since any error or bias introduced at this step could be amplified dramatically in subsequent steps, a carefully standardized procedure of sample preparation is required.  The critical issues are:

(1) what are the best methods that will minimize error or bias that may be introduced during whole genome amplification (WGA), and (2) how is cross-contamination prevented in the case that many individual samples are processed in a single pipeline?

Target capture. Ideally, all desired genome targets (e.g., all exons of protein coding RefSeq genes, not including predicted RefSeq genes) should be captured without any bias.  However, if achieving this goal is very costly, then what is the best trade-off between practicality and completeness in terms of accuracy, lack of bias, and reproducibility?  Are there practical methods for recovering missing sequence information?   How will consistency in the selection of regions be maintained from sample to sample?

Sequencing. What is the most cost-effective way to determine the sequence of the regions and enable reliable detection of individual sequence variation?  This question is particularly relevant because new sequencing platforms have just been introduced.  Critical issues are:

Quality.  What is the optimum quality of the sequence data for the purpose of this FOA?  Data should be of sufficient quality for the identification of sequence variants in diploid genomes.  It should also be of adequate quality for a range of downstream analyses.  How will sequence quality be measured?

Cost.  What is the cost of producing the data, and how can costs be reduced?  What are the specific components of the cost of sequencing?  What are the opportunities for reducing costs, and how should they be addressed?

Scalability. What is required so that the technology can be applied to the sequencing of thousands of individual samples in a relatively short period of time?

Integration of pipelines. How will sample preparation, target capture, and sequencing be integrated to attain the overall goals of this FOA?

5 Data management and analysis.  Critical issues are: (1) basecalling and standardized sequencing quality assessment; (2) data storage and retrieval; (3) monitoring and quality control of the pipeline process and data quality; and (4) methods for rapid mapping of short sequencing reads to the reference genome, identifying genomic variations (SNPs, but also indels and others), and monitoring target recovery and reproducibility rate of all sequenced samples. 

Research and Scope

The overarching goal of the research proposed under this FOA is to develop a new resequencing application using existing technologies to enable the resequencing of genome-wide medical targets (e.g., exome and microRNA) for thousands of DNA samples in well-phenotyped populations.  Specifically, the goal is to assemble current and emerging technologies and methodologies in four major areas - sample preparation, target capture, sequencing, and data management and analysis - into an integrated resequencing pipeline that has potential to reduce the cost approaching $1,000 per sample for sequencing 1% of the genome (60 Mb of diploid coverage).  Applicants should clearly describe the current cost and quality of targeted genome-wide resequencing of 1% of the genome (e.g., exome) and the strategy to reduce the cost towards $1,000 per sample.  The expectations outlined within this FOA are based on current knowledge and should be considered approximate, since the technologies related to these components are evolving at a rapid pace. 

In responding to this FOA, applicants should address all critical issues discussed in the Technology Components section.  It is anticipated that the research will take place in two-phases.  The first year could be an optimization phase to develop and optimize each of the four components and to integrate them into a production pipeline.  The DNA samples selected for this optimization phase should have pre-existing genome-wide genotyping or sequencing data (e.g., samples from HapMap project), to serve as a reference standard.  Some or all of these DNA samples will be shared among all awarded investigators.  Less than 20 DNA samples per investigator may be sufficient for this phase.  The second year could be the scale-up phase that will perform a feasibility study of the resequencing pipeline to determine if it can be applied to thousands of DNA samples.  The proposed sample size for this phase can be up to 100s of DNA samples per investigator.  However, the sample sources for this phase should not be specified in the proposal.  The NHLBI and NHGRI will work with awardees to select the samples that are scientifically informative and adequately consented.  The proposed scale-up phase could start at any time during the first or second year of the program.   

Applicants should propose to develop full-scale targeted resequencing systems, as outlined in the Technology Components section above.  Practical implementation issues related to workflow and process control should be considered early in system design.  Collaborations are encouraged.  For example, an investigator who has the infrastructure to carry out the research may seek co-investigator(s) with stronger expertise in any of the four components of the pipeline.  It is not a goal of this research to build capacity at the awardees’ institutions.  Therefore, applicants should have the entire infrastructure available to carry out the proposed work.

The application should include a description of the level of risk of key technical challenges, alternative approaches, go/no-go decision points, etc.  It should also include a detailed timeline accompanied by quantitative milestones that address the key scientific and technical challenges central to the approach. The quality and utility of the proposed timelines and milestones reflect the insights and judgment of the applicant concerning key challenges and how best to conduct the research. 

In order to compare different technology platforms that will be used in this program, the NHLBI and NHGRI will develop a common framework for comparison between awardees, especially to allow comparison of quality and cost.  For quality, this is likely to include evolving quality metrics for the new sequencing platforms, and also direct comparison of results (for example on shared samples).  For cost, it should include total cost per sample (direct and indirect) and the cost of each component. 

Program Organization:

The grants funded under this FOA will be R01 research grants.  Interaction among the participating investigators is required over a two-year period for developing and validating high-throughput cost-effective targeted resequencing systems.  Applicants should plan to attend grantee meetings, normally held in the Metropolitan Washington, D.C., area 2 times per year and monthly conference calls to share information in order to develop standard parameters and procedures of the system.  Grantee meetings will also be attended by NIH staff. Key co-investigators and pre- and postdoctoral trainees, in addition to the PIs, are eligible to attend these meetings. The cost of sending team members to attend these meetings should be included in the proposed research budget.

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

Section II. Award Information


1. Mechanism of Support

This Funding Opportunity Announcement (FOA) will use the NIH Research Project Grant (R01) award mechanism.   

The applicant will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses “Just-in-Time” information concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are a U.S. organization and are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, “Modular Budget Component,” of the Application Guide). 

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.      

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) are to provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The participating organizations, NHLBI and NHGRI, intend to commit approximately $6,000,000 dollars in fiscal year 2008 to fund 3-4 applications.

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.

F&A costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, November 2, 2004.  

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your institution/organization has any of the following characteristics:

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Applicants may not submit more than one application to this FOA. 

Section IV. Application and Submission Information


To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/applicants/apply_for_grants.jsp and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1.  Organizational/Institutional Registration in Grants.gov/Get Registered

2.  Organizational/Institutional Registration in the eRA Commons

3.  Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo: Telephone 301-435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components:

SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist

PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate required budget component.)  
Research & Related Budget (required for foreign applications)

Optional Components:

PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-domestic (non-U.S.) Entity)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from foreign organizations must:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS  

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” (Section 14 of the Research Plan Component in the SF424 [R&R]), must be included. A rationale for choosing a multiple PD/PI approach should be described.  The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan.  In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions 

When multiple institutions are involved, one institution must be designated as the prime institution, and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. 

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates

Opening Date:  January 28, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): January 28, 2008
Application Submission/Receipt Date(s): February 28, 2008
Peer Review Date(s): May-June, 2008
Council Review Date(s):August 2008
Earliest Anticipated Start Date(s): September 30, 2008

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

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

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp  and follow steps 1-4. Note:  Applications must only be submitted electronically.  PAPER APPLICATIONS WILL NOT BE ACCEPTED. 

In order to expedite the review, applicants are requested to notify the NHGRI Referral Office by email (pozzattr@mail.nih.gov) when the application has been submitted.  Please include the FOA number and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NHLBI and NHGRI.  Incomplete and non-responsive applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR receives the Grants.gov acknowledgments. The AOR and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons. 

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an “Introduction” describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

 4. Intergovernmental Review

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. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing renewal (formerly “competing continuation”) award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the
NIH Grants Policy Statement.

6. Other Submission Requirements

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

PHS398 Research Plan Component Sections

Items 2-5 of the PHS398 Research Plan component are limited to 25 pages. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.   

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts, and with the following additional requirements:

Special Instructions for Modular Grant applications

R01 applications from U.S. institutions/organizations requesting up to $250,000 per year in direct costs (excluding consortium F&A costs) must be submitted in a modular budget format. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm. When submitting a modular budget, the applicant organization will include only the PHS398 Modular Budget component. See Section 5.4 of the SF424 (R&R) Application Guide for further instructions regarding the use of the PHS398 Modular Budget component.

Foreign organizations may not submit modular budgets. See NOT-OD-06-096.   

Appendix Materials

NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Note: While each section of the PHS398 Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to monitor better formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

Foreign Applications (Non-domestic (non-U.S.) Entity)

Plan for Sharing Research Data

Applicants are required to describe their plan to share data at grantee meetings, and are required to describe plans to disseminate the technology and information about the technology that is being developed under this grant support.  The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing.  

The NIH is committed to the principle of rapid data release to the scientific community.  In their applications, all applicants need to indicate whether they are willing to abide by the proposed NIH data sharing policy for GWAS (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).  Applicants should address human subjects issues, including sharing phenotypic and genetic data from individual participants with the broad scientific community and ensure that the samples used in their studies have the appropriate consents for the data sharing policy.  The data is expected to be made available through an open access section of a database such as dbGaP, other public web sites, and/or publication in the scientific literature. 

Intellectual Property Policy: This FOA will support the development of a method(s) that can integrate technologies in four major areas - sample preparation, target capture, sequencing, and data management and analysis - into a high efficient resequencing pipeline.  This integration method should be freely accessible to the general scientific community so that it can be applied to large populations of many disease areas.   

The filing of patent applications and/or the enforcement of resultant patents in a manner that might restrict use of the method(s) could substantially diminish the utilization of it to many disease areas and the potential public benefit they could provide. Approved Users and Investigators supported under this FOA, and their institutions, should acknowledge the program’s IP Policy, the goal of which is to ensure the greatest possible public benefit from the development of this resequencing application. 

Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement  http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., “Reporting.”

Section V. Application Review Information


1. Criteria 

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHGRI in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

Innovation:  Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators: Are the PD/PI(s) and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the PD/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment:  Do(es) the scientific environment(s) in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?  

2.A. Additional Review Criteria

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed.  See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R).
 
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the adequacy of the plans for their care and use will be assessed. See the “Other Research Plan Sections” of the PHS398 Research Plan component of the SF424 (R&R). 

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed. 

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590), See Section VI.3., “Reporting.” 

Model Organism Sharing Plan: Reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations.

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information


1. Award Notices

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 NIH eRA Commons

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., “Funding Restrictions.”       

2. Administrative and National Policy Requirements

Prior to funding an application, the NHLBI may negotiate the milestones with the applicant, beginning with the applicant ’s stated milestones and incorporating recommendations from the review panel and staff.  The negotiated milestones will become a condition of the award, including appropriate language to recognize that the project includes research whose outcomes are unpredictable.

To accelerate progress in the field of advanced targeted DNA resequencing technology development, grantees will be expected to participate actively and openly in at least two grantee meeting per year.  Substantial information sharing will be required and is a condition of the award.  Applicants may wish to consult with their institution's technology transfer office for guidance in managing any intellectual property issues that may arise in the development of the participation plan. 

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.

3. Reporting

Applicants must plan to submit one progress report per year at the time of the non-competing continuation.  Other reports may be required to enable management of this program towards developing and validating high-throughput and cost-effective targeted resequencing systems.  The NHLBI and NHGRI will use information from reports, meetings, site visits, etc. to evaluate each grantee’ progress and the success of the overall program; this information will be used to determine if funding levels should be increased or decreased for future years, for each grant, and for the program.

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

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Weiniu Gan, Ph.D.
Division of Lung Diseases
National Heart, Lung and Blood Institute
6701 Rockledge Dr. MSC 7952
Bethesda, Maryland 20892-7952
Telephone:   (301) 435-0202
Email:  ganw2@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

Adam L. Felsenfeld, Ph.D.
Large-scale Sequencing
National Human Genome Research Institute
Building 31, Room B2B07
45 Center Drive
Bethesda, MD 20892-2033
Telephone:  (301) 496-7531
Email:  adam_felsenfeld@nih.gov

2. Peer Review Contact(s):

Rudy Pozzatti, Ph.D.
Scientific Review Branch
National Human Genome Research Institute, NIH
5635 Fishers Lane, Suite 4076
Bethesda, MD 20892-9306 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service, non-USPS service)
Telephone:  (301) 402-0838
E-mail:  pozzattr@mail.nih.gov

3. Financial/Grants Management Contact(s):

Ryan Lombardi
Grants Operations Branch
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
Rockledge II, Room 7154
6701 Rockledge Drive
Bethesda, MD 20892
Telephone: (301) 435-0144
FAX: (301) 480-3310
Email: lombardr@nhlbi.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, state and federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: (a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and (b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov/) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from (1) currently funded NIH research projects or (2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov// and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information," the "Privacy Rule," on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:

All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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