text:
Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)
Components of
Participating Organizations
National Human Genome Research Institute (NHGRI), (http://www.nhgri.nih.gov)
Title: Revolutionary Genome Sequencing Technologies – The $1000 Genome (R01)
This Funding Opportunity Announcement (FOA) is a reissue of RFA-HG-09-011.
Update: The following updates relating to this announcement have been issued:
Request for Applications (RFA) Number: RFA-HG-10-012
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.
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 (4) weeks prior to the grant submission date. See Section IV.
Catalog of Federal Domestic Assistance Number(s)
Key Dates
Release/Posted Date: August 27, 2010
Opening Date: September 19, 2010 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Dates: September 19, 2010; September 18, 2011; September 17, 2012
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 Due Dates: October 19, 2010 (Changed to November 1, 2010 per NOT-HG-10-021); October 18, 2011; October 17, 2012
Peer Review Dates: March 2011; March 2012; March 2013
Council Review Dates: May 2011; May 2012; May 2013
Earliest Anticipated Start Dates: July 1, 2011; July 1, 2012; July 1; 2013
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: October 18, 2012
Due Dates for E.O. 12372
Not Applicable
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. Receipt, 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
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
Research Objectives
The National Human Genome Research Institute (NHGRI) solicits R01 grant applications to develop novel technologies that will enable extremely low-cost, high quality DNA sequencing. This FOA continues a program that began in 2004, when the cost to produce a high quality draft mammalian genome sequence was estimated at $5 to $10 million, and the goal of was to reduce costs by four orders of magnitude – to approximately $1,000 – in ten years.
While substantial progress toward the $1,000 genome has been made, daunting scientific and technical challenges remain. This program will continue to support both fundamental scientific investigation underlying the technologies, and their engineering, to achieve this goal. The program supports development of key system components and of full systems. In this context, 'key components' refers to the method for determining the linear order of nucleotides, in contrast to upstream or downstream steps in sequencing. Exploration of methods other than those currently being pursued as potential $1,000 genome technologies is encouraged. High-risk/high-payoff proposals are appropriate to achieve the goals of this FOA by approximately 2014.
Parallel FOAs of identical scientific scope (RFA-HG-10-013 and RFA-HG-10-014) solicit applications under the R21 and Small Business Innovation Research (SBIR) grant programs, respectively.
The ability to sequence complete genomes and the free dissemination of sequence data have dramatically changed the nature of biological and biomedical research. Sequence and other genomic data have the potential to lead to remarkable improvement in many facets of human life and society, including the understanding, diagnosis, treatment and prevention of disease; advances in agriculture, environmental science and remediation; and our understanding of evolution and ecological systems.
The ability to sequence many genomes completely has been made possible by the enormous reduction of the cost of sequencing in the past 30 years, from tens of dollars per base in the 1980s to a fraction of a cent per base today. We have progressed from the early Human Genome Project goals to sequence the genomes of the human and mouse and a few additional model organisms (E. coli, C. elegans and D. melanogaster), through programs to sequence at varying pre-determined quality levels numerous genomes across the evolutionary tree including multiple species and variants for some of those, to current programs to sequence portions or the entire genomes of increasing numbers of tumors and human individuals. Technology advances, and in particular the recent emergence of a new generation of sequencing systems, have enabled the launch of several such projects that are producing stunning insights into biology and disease. Nevertheless, the cost to completely sequence large numbers of entire genomes remains too high to allow complete genome sequencing to be used routinely, and we remain far from achieving the low costs and high quality needed to enable the use of comprehensive genomic sequence information in individual health care.
A few examples of high priority research to which genomic sequencing at high quality and dramatically reduced cost would make vital contributions include:
The broad utility and high importance of dramatically reducing DNA sequencing costs prompted the NHGRI, in 2004, to embark on two parallel technology development programs (Nature Biotech. 26:1113, 2008). The first had the objective of reducing the cost of producing a high quality sequence of a mammalian-sized genome by two orders of magnitude, to about $100,000. This goal has been achieved so no additional grant applications are being solicited at this time. Rather, the NHGRI is focusing its efforts on attaining the goal of the second program, which, as described in this FOA and parallel FOAs for other grant mechanisms, is the development of technologies with which to sequence a human genome for about $1,000 (a four order of magnitude cost reduction). Implicit in this goal is the quality of the expected sequence product, as sequencing cost targets are meaningless without associated quality standards as described below.
Sequencing Strategy and Quality
The sequencing technology that was used to produce the reference human genome sequence (Nature 431:931, 2004; Nature 409:860, 2001; Science 291:1304, 2001) was fluorescence detection of dideoxynucleotide-terminated DNA extension reactions resolved by capillary array electrophoresis (CAE). Individual sequence "read" segments can be as long as 1000 nucleotides. If all of the DNA in a 3 Gb genome were unique, it would be possible to determine the sequence of the entire genome by generating a sufficient number (tens of millions) of randomly-overlapping 1000-base reads and aligning their overlaps. However, the human and the majority of other interesting genomes contain a substantial amount of repetitive DNA. To cope with the complexities of repetitive DNA elements and to assemble the thousand-base reads in the correct long-range order across the genome, genomic sequencing methods involve a variety of additional strategies, such as the sequencing of both ends of cloned DNA fragments, use of libraries of cloned fragments of specified lengths, incorporation of map information, achievement of substantial redundancy (multiple reads of each nucleotide from overlapping fragments) and application of sophisticated assembly algorithms to filter and align the reads. As new sequencing technologies are developed, they must incorporate means to deal with these features of the structure of the genome.
The gold standard for genomic sequencing is based on the above-described methods and remains =99.99% accuracy (not more than one error per 10,000 nucleotides) with essentially no gaps (http://www.genome.gov/10000923). The "finishing" steps needed to achieve that very high quality have not been automated and thus require substantial hand-crafting. However, experience shows that much comparative and medically useful sequence information can be obtained from automatically generated sequence assemblies that are known as "high-quality draft" or "comparative grade." Therefore, the cost targets for NHGRI's sequencing technology development programs were originally defined in terms of a mammalian-sized genome with a sequence quality equivalent to or better than that of the mouse draft assembly published in December 2002 (Nature 420:520, 2002). Producing such a product for $1,000 is still not possible, so this remains a useful and challenging technology target. However, it is critical to note that the ultimate need, for medical research and individualized medicine, will be for far higher quality sequence of the 3 Gb diploid human genome
Subsequent to dideoxy/CAE sequencing, a second generation of sequencing technologies has been developed and implemented. These are broadly described as array-based methods in which large numbers of templates are extended one base at a time, the extensions are detected, and that cycle is repeated (reviewed in Nature Biotechnology October 2008). These technologies enable the sequencing of larger numbers of genomes for under $100,000 dollars each, and even less for targeted sequencing of particular genomic regions. While challenges remain related to producing and interpreting sequence information using these technologies, they are proving invaluable to the biomedical research enterprise and they validate the impetus toward further substantial decreases in cost with increases in quality, throughput and speed of genomic sequencing.
The eventual goal of these programs is to achieve technologies that can produce assembled sequence of genomes that had not been previously sequenced (i.e., de novo sequencing). However, an accompanying goal is to obtain highly accurate sequence data at the single base level that can be overlain on a reference sequence of the organism (i.e., re-sequencing). This could be achieved, for example, with short reads that lack information linking them to other reads. In spite of shortcomings (some of which are described below), re-sequencing would potentially be available sooner and of considerable value for certain studies on disease etiology and individualized medicine. Therefore, technology development for re-sequencing will be supported under this FOA. As the cost goal for the more difficult challenge, de novo assembly sequencing, is $1,000, the goal for re-sequencing is to develop technologies that will provide a genome's worth of less-well-mapped sequence for well below $1,000.
For re-sequencing, the per-base accuracy must be sufficient to distinguish between sequencing errors and real polymorphism. Additional challenges include assigning reads to gene families with very similar sequence, the identification of copy number changes and genomic rearrangements, and the identification of haplotypes (i.e., linear juxtapositioning of particular single nucleotide polymorphism [SNP] alleles along a single chromosome) in diploid organisms. Thus, in proposing the development of re-sequencing technologies, it is essential that the applicant clearly address the extent to which the proposed technology will meet or fall short of these various challenges, and the cost tradeoffs that justify developing the technology to produce data of high value for particular biomedical studies.
Research and Scope
The goal of research supported under this FOA is to develop new or improved technology to enable rapid, efficient DNA sequencing of mammalian-sized genomes. The target cost for a 3 Gb diploid genome sequence determined at reasonably high quality is about $1,000 because the ability to generate routinely complete genomic sequences at that cost would revolutionize biological research and medicine.
Both fundamental scientific discovery and cutting edge engineering will likely be needed to achieve these goals. For example, new sensing and detection modalities and fabrication methods may be required, and the physics of systems operating at nm length scales will need to be better understood. It is therefore anticipated that proposals responding to this FOA will involve fundamental and engineering research conducted by multidisciplinary teams of investigators. The guidance for budget requests accommodates the formation of groups having investigators at several institutions, in cases where that is needed to assemble a team of the appropriate balance, breadth and experience.
The scientific and technical challenges inherent in achieving the cost goals are significant. Achieving these goals may require research projects that entail substantial risk. That risk should be balanced by an outstanding scientific and management plan designed to achieve the very high payoff goals of this solicitation. High-risk/high-payoff projects may fail for legitimate reasons, so applicants proposing such projects should identify them as such, elaborate key quantitative milestones to be achieved, and describe the consequences of not achieving those milestones in a reasonable period of time.
Applicants may propose to develop full-scale sequencing systems or investigate key components of such systems. For the latter, applicants must describe how the knowledge gained as a result of the proposed project would be incorporated into a full system that they or others might subsequently propose to develop. Such independent proposals are an important path for pursuing novel, high-risk/high-payoff ideas, short of developing a full system.
While the major focus of this program is on the development of new technologies for detection of nucleotide sequence, any successful technology will have to address matters related to the practical implementation of the technologies so that the technology can form the basis of, or be incorporated into, an efficient, high quality, high-throughput DNA sequencing scheme. Any new technology will eventually need to be incorporated effectively into a sequencing workflow, starting with a biological sample and ending with sequence data of the desired quality. Sample preparation requirements can depend upon the detection method which, in turn, can affect the way in which output data are handled. If a full system development is proposed, these issues should be addressed on an appropriate schedule in the research plan; applicants should focus as early as possible in the research plan on the most critical and highest-risk aspects of the project related to determining the sequence of nucleotides, on which the rest of the project depends. Projects to address key components must address the fundamental method of determining the base sequence (that is, a proposal addressing only sample prep or only the downstream informatics would not be considered responsive to this FOA).
Most technology developers lack practical experience in high-throughput sequencing and in testing of methods and instruments for robust, routine sequencing operation. Applicants may therefore wish to include such expertise as they develop their teams. Academic investigators may wish to consider collaborating with commercial entities that have the experience and capabilities to bring practical systems into the hands of users.
The quality of sequence to be generated by the technology is of paramount importance for this solicitation. Two major factors contributing to genomic sequence quality are per-base accuracy and contiguity of the assembly. Much of the utility of comparative sequence information will derive from characterization of sequence variation between species, and between individuals of a species. Therefore, per-base accuracy must be high enough to discern polymorphism at the single-nucleotide level (substitutions, insertions, deletions) and distinguish polymorphism from sequencing errors. Experience and resulting policy have established a target accuracy of not more than one error per 10,000 bases. All applications in response to this FOA, whether to develop re-sequencing or de novo sequencing technologies, must propose to achieve at least this standard.
Assembly information is needed for determining sequence of new genomes and ultimately also for genomes for which a reference sequence exists, to detect rearrangements, insertions, deletions, and copy number changes. All of these are genomic changes have been shown to be associated with disease, and knowledge of rearrangements can reveal new biological mechanisms. The phase of single nucleotide polymorphisms to define haplotypes is important in understanding and diagnosing disease. Achieving a high level of sequence contiguity may be essential to achieve the full benefit from the use of sequencing for individualized medicine, e.g., to evaluate genomic contributions to risk for specific diseases and syndromes, and drug responsiveness. Nevertheless, it is recognized that perfect sequence assembly from end to end of each chromosome is unlikely to be achievable with most technologies in a fully automated fashion and without adding considerable cost. Therefore, for the purpose of this solicitation, grant applications proposing technology development for de novo sequencing shall describe how they will achieve, for about $1,000, a draft-quality assembly that is at least comparable to that represented by the mouse draft sequence produced by December 2002: 7.7-fold coverage, 6.5-fold coverage in Q20 bases, assembled into 225,000 sequence contigs connected by at least two read-pair links into supercontigs [total of 7,418 supercontigs at least 2 kb long], with N50 length for contigs equal to 24.8 kb and for supercontigs equal to 16.9 Mb (Nature 420:520, 2002). Grant applications that propose technology development for re-sequencing should fully describe the qualities and characteristics of the genomic sequence information that the technology would produce, and the projected cost. That cost should be at least four orders of magnitude lower than was the cost to produce comparable quality data in 2004, when this program was initiated.
Grant applications will be evaluated, and funding decisions made, in such a way as to develop a balanced portfolio that has strong potential to develop both robust de novo and re-sequencing technologies, exploring a variety of technology approaches. If the estimate is correct, that achieving the goal of $1,000 de novo genome sequencing incorporating substantial assembly information will be achieved by about 2014, then low-cost re-sequencing technologies for even lower cost might be expected in a shorter time. Projects with a plan to achieve re-sequencing while on the path to de novo sequencing will receive priority.
Research conducted under this FOA may include development of the computational tools associated with the technology, e.g., to extract sequence information, including image analysis and signal processing, and to evaluate sequence quality and assign confidence scores. It may also address strategies to assemble the sequence from the information being obtained from the technology or by merging the sequence data with information from parallel technology. Applications that incorporate effective plans to develop systems that address the bioinformatics challenges in concert with the sequencing wet-ware will receive high priority consideration. However, this FOA will not support development of sequence assembly or sequence analysis software independent of technology development to obtain the linear nucleotide sequence.
This program is aimed at technology to sequence entire genomes. Projects are under way to determine sequence from selected important regions (e.g., all of the genes). Grant applications that propose to meet the cost targets by sequencing only selected regions of a genome will be considered unresponsive to this FOA. However, applications that propose novel ways to sequence selected genomic regions, cost-effectively, while on a path to whole-genome sequencing, will be considered to be responsive.
NHGRI is interested in supporting diverse approaches to achieving the goals of this FOA. To assist the research community, investigators who are pursuing one set of technology paths that involve the use of nanopores and nanogaps published an overview of the challenges they face (Nature Biotech. 26:1146, 2008). Similarly, challenges attending sequencing by synthesis have been described (Nature Biotech. 27:1013, 2009). Proposals to meet these and related challenges, and proposals to pursue alternative technologies, are welcome under this FOA. Information on projects funded under earlier versions of this and related FOAs and a program bibliography are available at http://www.genome.gov/10000368#6.
See Section VIII, Other Information
- Required Federal Citations, for policies related to this announcement.
Section II. Award Information
1. Mechanism of Support
This FOA will use the R01 award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.
This FOA uses "Just-in-Time" information concepts (see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see https://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) must use the PHS398 Modular Budget component.
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.
Funds Available
NHGRI intends to commit approximately $5 million total costs in each of fiscal years 2011, 2012 and 2013 to fund 2-7 applications each year. An applicant may request a project period of up to 4 years and a budget for direct costs up to $1.5 million per year.
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 IC(s) provide support for this
program, awards pursuant to this funding opportunity are contingent upon the
availability of funds.
and Administrative (F&A) costs requested by consortium participants are not
included in the direct cost limitation. See NOT-OD-05-004.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Section III. Eligibility Information
Eligible Applicants
1.A. Eligible Institutions
The following organizations/institutions are eligible to apply:
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 (i.e., multiple PDs/PIs), may be designated on the application for projects that require a "team science" approach and therefore clearly do 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 https://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (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 grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering the multiple PD/PI option, 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 PDs/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 https://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
Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct.
Resubmissions. Applicants may submit a resubmission application only if the original application had been submitted to the previous issuances of this RFA (RFA-HG-09-011), but such application must include an Introduction addressing the previous peer review critique (Summary Statement). Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and renewal applications are permitted only a single amendment (A1). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016). Original new and renewal applications that were submitted prior to January 25, 2009 are permitted two amendments (A1 and A2). For these "grandfathered" applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date.
Renewals. Renewal applications will be permitted for this FOA.
Section IV. Application and Submission Information
download a SF424 (R&R) Application Package and SF424 (R&R) Application
Guide for completing the SF424 (R&R) forms for this FOA, use the "Apply for
Grant Electronically" button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.
Appropriate registrations with Grants.gov and eRA Commons must be completed on or before the due date in order to successfully submit an application. 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 with both Grants.gov and the Commons. All registrations must be complete by the submission deadline for the application to be considered "on-time" (see 3.C.1 for more information about on-time submission).
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 NIH eRA Commons.
Several additional separate actions are required before an applicant 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 PDs/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.
Note: The registration process is not sequential. Applicants should begin the registration processes for both Grants.gov and eRA Commons as soon as their organization has obtained a DUNS number. Only one DUNS number is required and the same DUNS number must be referenced when completing Grants.gov registration, eRA Commons registration and the SF424 (R&R) forms.
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
For further assistance, contact GrantsInfo -- Telephone 301-710-0267; Email: firstname.lastname@example.com.
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 for this FOA through Grants.gov/Apply and in accordance with the SF424 (R&R) Application Guide (https://grants.nih.gov/grants/funding/424/index.htm).
The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within the SF424 (R&R) application components, 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 regarding appropriate required budget component.)
Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form
Organizations (Non-Domestic
[non-U.S.] Entities)
NIH policies concerning grants to Foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: https://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 (U.S.) or that augment existing U.S. resources.
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 on 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.
Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the section of the Research Plan entitled, "Multiple PD/PI Leadership Plan", 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, and should include 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 (NoA).
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.
Submission Dates and Times
See Section IV.3.A. for details.
3.A. Submission, Review, and Anticipated Start Dates
Opening Date: September 19, 2010 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Dates: September 19, 2010; September 18, 2011; September 17, 2012
Application Due Dates: October 19, 2010; October 18, 2011; October 17, 2012
Peer Review Dates: March 2011; March 2012; March 2013
Council Review Dates: May 2011; May 2012; May 2013
Earliest Anticipated Start Dates: July 1, 2011; July 1, 2012; July 1; 2013
3.A.1. Letter of Intent
Prospective applicants are asked to submit a letter of intent that includes the following information:
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:
Jeffery A. Schloss, Ph.D.
Division of Extramural Research
National Human Genome Research Institute, NIH
5635 Fishers Lane, Suite 4076
Bethesda, MD 20892-9305
Telephone: (301) 496-7531
Email: email@example.com- please transmit Letter of Intent by email.
3.B. Submitting an Application Electronically to the
To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/web/grants/applicants/apply-for-grants.html and follow Steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED. 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.
In order to expedite the review, applicants are requested to notify the NHGRI Referral Office by email (email@example.com) when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Application Processing
3.C.1 Submitting On-Time
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 due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed. All applications must meet the following criteria to be considered "on-time":
Please visit http://era.nih.gov/electronicReceipt/app_help.htm for detailed information on what to do if Grants.gov or eRA system issues threaten your ability to submit on time.
Submission to Grants.gov is not the last step – applicants must follow their application through to the eRA Commons to check for errors and warnings and view their assembled application!
3.C.2 Two Day Window to Correct eRA Identified Errors/Warnings
IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.
Once an application package has been successfully submitted through Grants.gov, NIH provides applicants a two day error correction window to correct any eRA identified errors or warnings before a final assembled application is created in the eRA Commons. The standard error correction window is two (2) business days, beginning the day after the submission deadline and excluding weekends and standard federal holidays. All errors must be corrected to successfully complete the submission process. Warnings will not prevent the application from completing the submission process.
Please note that the following caveats apply:
3.C.3 Viewing an Application in the eRA Commons
Once any eRA identified 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 weekdays (Monday – Friday, excluding Federal holidays) to view the assembled application before it automatically moves forward to NIH for further processing.
Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the IC. Incomplete and/or 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/SO receives the Grants.gov acknowledgments. The AOR/SO 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 the application status in the Commons.
The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.
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 renewal award if such costs: 1)
are necessary to conduct the project, and 2) 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 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
Supplementary Instructions
A detailed research plan must be presented. 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 (see below) that address the key scientific and technical challenges central to the approach. The timeline and milestones are essential for use by the grantee and the NHGRI for planning the research project and assessment of progress toward goals, and by the reviewers for evaluating the proposal.
Timelines and quantitative milestones are essential for development of a realistic research plan; they provide a basis for project leaders to make decisions, assess their own progress, set priorities, and redistribute resources when needed. It will be particularly important to establish quantitative milestones in cases where subsequent steps in technology development depend upon threshold performance characteristics of earlier developments. Elaboration of timelines and milestones is primarily the responsibility of the applicant, and the quality and utility of the proposed timelines and milestones will be a review criterion, because they reflect the insights and judgment of the applicant concerning key challenges and how best to conduct the research. The NHGRI appreciates that these projects will require research, not just engineering; progress toward milestones will be evaluated accordingly. If the proposed timeline and milestones are not adequate in the case of an otherwise meritorious proposal, reviewers of the application may make recommendations to NHGRI regarding improved timelines and milestones.
Projects that propose to build sequencing systems (in contrast to developing components) that will be assembled by the end of the project period may wish to present a strong case for that system's capabilities by proposing to demonstrate the sequencing of a substantial amount of DNA (e.g., mega- to gigabases) at the target cost and quality; other measures may be proposed by the applicant.
To accelerate progress in the field of advanced DNA sequencing technology development, grantees will be required to participate actively and openly in at least one grantee meeting per year. Substantial information sharing will be required and is a condition of the award; failure to openly share information will be grounds for discontinuation of funding. It is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the technology. Applicants should describe their plans for participating in the grantee meetings and for managing the intellectual property concerns in the context of those meetings and other opportunities for information sharing. Other investigators in the field (i.e., not supported under this program) may be invited to participate in these workshops; their agreement to share information substantially will be a prerequisite to participation. Applicants should request travel funds in their budgets for the Principal Investigator and two additional lead investigators to attend the annual meetings.
Applicants must describe their plan for providing access to the technology developed under this grant support, and information about that technology. For example, the technology might be made available as a fee-for-service, through sale of instruments and/or reagents, through collaboration, through publication and posting of results, plans and methods, or by other means. If any quantity of sequence data will be collected under grant support, a plan to disseminate those data must be described.
Applicants may include funds for an internally appointed advisory board. However, they should not contact potential advisors, nor should potential advisors be named in the grant application, to avoid conflicts of interest in the review process.
In summary, applicants must incorporate into the Approach section of the Research Strategy:
In addition to the Research Strategy section, applicants must include, in the application fields designated below, the following management plan information:
Include in Item 12, "Multiple PD/PI Leadership Plan" under "Other Research Plan Sections:"
Include in Item 15, "Resource Sharing Plan" under "Other Research Plan Sections:"
DNA sequencing technology research is advancing at an astounding pace (e.g., http://genomebiology.com/2010/11/5/207). Therefore, NHGRI will accept brief updates incorporating new insights or results directly pertinent to material already submitted in the original application. Updates are limited to 2 pages for R01 applications (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-10-115.html).
PD/PI Credential (e.g., Agency Login)
The NIH requires the PD(s)/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
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:
Budget Component
U.S. applicants submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) must use the PHS398 Modular Budget component.
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.
Applicants should include travel funds for the participation of the Principal Investigator and up to two additional colleagues to participate in annual grantee meetings.
Appendix Materials
Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See https://grants.nih.gov/grants/funding/424/index.htm).
Do not use the Appendix to circumvent the page limitations.. An application that does not comply with the required page limitations may be delayed in the review process.Resource Sharing Plan(s)
NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this should be explained in the Resource Sharing section of the application (see https://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)
(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)
(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NOT-OD-04-042.)
(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and https://grants.nih.gov/grants/gwas/.)
Describe your commitment to sharing information at grantee meetings, and for providing access to the technology and to information about the technology, as discussed above in Section 6. Other Submission Requirements, Supplementary Instructions.
Foreign Applications (Non-Domestic [non-U.S.] Entities)
Indicate how the proposed project has specific relevance to the mission and objectives of the NIH/IC and has the potential for significantly advancing the health sciences in the United States.
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
Review Process
Applications that are complete and responsive to this FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHGRI and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.
As part of the scientific peer review, all applications will:
The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Overall Impact
Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five scored review criteria, and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
Reviewers will consider each of the five review criteria below in the determination of scientific and technical 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?
Additional Review Criteria
As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, 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.
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.
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, see https://grants.nih.gov/grants/olaw/VASchecklist.pdf.
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.
Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewal Applications. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.
Revision Applications. When reviewing a Revision application (formerly called a competing supplement application), the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident. Revisions are permitted only if the original application had been awarded in response to previous issuances of this FOA (RFA-HG-09-011).
Additional Review Considerations
As applicable for the project proposed, reviewers will address 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. As applicable for the FOA or submitted application, 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 Agents 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 (https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).
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.
Selection Process
Applications submitted in response to this FOA will compete for available funds with all other recommended applications submitted in response to this FOA. The following will be considered in making funding decisions:
Anticipated Announcement and Award Dates
Not Applicable
Section VI. Award Administration Information
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.
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 NHGRI will negotiate the milestones with the applicant, beginning with the applicant's stated milestones and incorporating recommendations from the review panel, the National Advisory Council for Human Genome Research, 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. In the case of research programs projected to require longer than the initial grant period, the decision to fund beyond the initial period will be based on a competitive renewal process that will take into account overall progress in the field as well as progress on the individual research effort, as compared to the negotiated milestones.
To accelerate progress in the field of advanced DNA sequencing technology development, grantees will be expected to participate actively and openly in at least one grantee meeting per year. Substantial information sharing will be required and is a condition of the award; failure to openly share information will be grounds for discontinuation of funding. It is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the technology. Applicants should describe their plans for participating in the grantee meetings and for managing the intellectual property concerns in the context of those meetings and other opportunities for information sharing. Other investigators in the field (i.e., not supported under this program) may be invited to participate in these workshops; their agreement to share information substantially will be a prerequisite to their participation. The applicant's participation plan, after negotiation with NHGRI staff, will become the minimum standard for continued funding.
Grantees may be asked to host the annual grantee meetings on a rotating basis. The NHGRI will negotiate a schedule for the grantee meetings and will adjust budgets to accommodate these meetings. Holding these meetings at grantee sites or in association with other meetings will facilitate information sharing and participation of a larger portion of the research staff than would otherwise occur.
The applicant's plans, as negotiated with staff, for complying with timelines and milestones, participation in grantee meetings, submitting progress reports, and sharing research data will be conditions of the award.
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.
Applicants should plan to submit two progress reports per year – one at the time of the non-competing continuation and one at a time to be determined by NHGRI staff. The latter may coincide with grantee meetings, meetings of advisors to NHGRI, or site visits. The NHGRI will use information from reports, meetings, site visits, etc. to evaluate each grantee's 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.
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 your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:
1. Scientific/Research Contact(s):
A. Schloss, Ph.D.
Division of Extramural Research
National Human Genome Research Institute, NIH
5635 Fishers Lane, Suite 4076
Bethesda, MD 20892-9305
Telephone: (301) 496-7531
Email: email@example.com
2. Peer Review Contact(s):
Nakamura, 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: firstname.lastname@example.com
3. Financial/Grants Management Contact(s):
Grants Administration Branch
National Human Genome Research Institute, NIH
5635 Fishers Lane, Suite 4076
Bethesda, MD 20892-9306
Phone: (301) 435-7858
Fax: (301) 402-1951
E-mail: email@example.com
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 (https://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (https://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
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, https://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 (https://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule.
Policy for Genome-Wide
Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see https://grants.nih.gov/grants/gwas/.
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 https://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.
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 https://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.
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" (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at https://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 (https://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 https://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 https://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.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.
NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicine's PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.
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).
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text:
Psalms 56
1. To the chief Musician upon Jonathelemrechokim, Michtam of David, when the Philistines took him in Gath. Be merciful unto me, O God: for man would swallow me up; he fighting daily oppresseth me.
Mine enemies would daily swallow [me] up: for [they be] many that fight against me, O thou most High.
What time I am afraid, I will trust in thee.
In God I will praise his word, in God I have put my trust; I will not fear what flesh can do unto me.
Every day they wrest my words: all their thoughts [are] against me for evil.
They gather themselves together, they hide themselves, they mark my steps, when they wait for my soul.
Shall they escape by iniquity? in [thine] anger cast down the people, O God.
. Thou tellest my wanderings: put thou my tears into thy bottle: [are they] not in thy book?
When I cry [unto thee], then shall mine enemies turn back: this I know; for God [is] for me.
In God will I praise [his] word: in the LORD will I praise [his] word.
In God have I put my trust: I will not be afraid what man can do unto me.
Thy vows [are] upon me, O God: I will render praises unto thee.
For thou hast delivered my soul from death: [wilt] not [thou deliver] my feet from falling, that I may walk before God in the light of the living?
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Psalm 57
Go to
The Book
opening page.

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text:
Imagine if any political leader would say: "No blacks will be allowed to live in my state". He would be denounced correctly, as a racist, a bigot.
That does not seem to include Mahmoud Abbas, the Palestinian Arab leader of Ramallah, who on the verge of the new "peace talks" in Washington just declared: "In a final resolution, we would not see the presence of a single Israeli - civilian or soldier - on our lands".
This is not "peace", but pure Nazism, it is ethnic cleansing. And instead of the expression "final resolution", Abbas should have said what he really means, "final solution".
Addressing a session of Arab League in Doha, Qatar, Abbas in 2011 declared that "when an independent Palestinian state with Jerusalem as its capital is established, we won't allow the presence of one Israeli in it".
A Palestinian Arab State on Western Eretz Israel would be "jüdenrein", or cleansed of Jews. A state founded on the ethnic cleansing of every single Jewish man, woman and child.
How can you call "peace" a deal in which hundreds of thousands of Jews surrender to expulsion or to becoming refugees like "lambs to the slaughter"?
Can you imagine if Benjamin Netanyahu instead of Mahmoud Abbas would have pronounced such a statement? What would have been the world reaction?
And Abbas said it in front of the long European noses. He proclaimed his Nazi intentions while in Cairo. Lady Ashton, the ridiculous EU foreign chief, was present.
But we must thank Mr. Abbas, because he said clearly that the "State of Palestine" and the Jewish presence in Judea and Samaria are exclusive. Israel would have to uproot all the Hebrew towns in order to pave the way for this "peace", which is in fact the new apartheid that he hopes will come into existence upon the ruins of the "settlers'" homes.
What Abbas said is the same message repeated from the Palestinian Arab mosques and streets: "Idbach al Yahud !" (Slaughter the Jews), "Mauwt al Yahud !" (Kill the Jews), "Falastin baladna, al Yahud kalabna" (Palestine is our homeland, the Jews are our dogs).
The PLO Covenant rejects the idea that Jews have any "historical or religious ties" to the land, since "Judaism, being a religion, is not an independent nationality".
Isn't it pure Nazism?
PLO's Article Six declares: "The Jews, who had normally resided in Palestine until the beginning of the Zionist invasion (usually dated as the mid-19th century) will be considered Palestinians". In other words, 98 per cent of the existing Israeli Jewish population must be banished like, like the 8.000 Jews of Gush Katif. Or killed, like the Fogels of Itamar.
The PA's mufti of Jerusalem, Sheikh Ikremah Sabri, and the Palestinian chief Islamic judge, Sheikh Tayseer Tamimi, issued decrees authorizing the killing of Arabs who sell property to Jews and forbidding Muslims from burying them in Islamic cemeteries. Not even Nazi Germany in the 1930s knew this level of anti-Jewish pathology.
Or take the 'refugee' question. The PLO manifesto claims that the"Palestinian personality" is an "innate, persistent characteristic that does not disappear . . . and is transferred from fathers to sons" (No. 4). And what if all Palestinians had emigrated, or had become refugees from the land? They would still belong to "Palestine" along with their male descendants. Forever. This is like the Nazi "Drang Nach Osten" and "Blut und Erde".
Abbas and other PLO terrorists are asking Israel and the United States to expel all the Jews, from the youngest to the oldest, so the Hebrew people will be stained by their presence.
If you assume that Area A and Area B are no longer negotiable, which is not true, note that 60 percent of Judea and Samaria is already free of Jews. And with the exception of the Jewish city of Hevron, there are no Jewish citizens in the big Arab cities, Nablus, Jenin, Ramallah, Tulkarem, Qalqilia. And also in Hevron, the city of the Patriarchs you have "Area A" (or H1), the jüdenrein part of Hevron.
To return to the "peace talks", what are these all about? The division of Jerusalem? Maybe, but only in a suicidal end game. The 'return' of the 'refugees'? Certainly not. These talks, like all the previous ones, are about the percentage of Jews of Judea and Samaria to be ghettoized, deported, killed and expelled.
The "State of Palestine" would be the carbon copy of Hans Frank's General Government in Poland. Two thirds of the nations of the world, represented in the United Nations, support the establishment of a state that would be, by definition, the first to officially prohibit Jews or any other faith since Nazi Germany.


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PITTSBURGH — The New York Islanders' turnaround season is heading to the second round of the playoffs.
Jordan Eberle scored for the fourth straight game, Robin Lehner stopped 32 shots and the Islanders finished off Sidney Crosby and the Pittsburgh Penguins with a clinical 3-1 win in Game 4 on Tuesday night to pull off a stunning sweep.
Josh Bailey set up Brock Nelson's go-ahead goal late in the first period and added an empty-net score with 38 seconds remaining as the Islanders easily captured the franchise's second playoff series victory in 26 years.
The Islanders trailed for less than five minutes across four games against the Penguins, whose 13th straight post-season appearance ended quietly. Pittsburgh managed just six goals in the series, including Jake Guentzel's first of the post-season 35 seconds into the game.
It wasn't nearly enough to stop the Islanders. New York allowed the fewest goals in the league during the regular season, and then backed it up with 12-plus periods of sound hockey that's quickly become their calling card under first-year coach Barry Trotz, who led the Washington Capitals to the Stanley Cup last season.
The Penguins did their best to stay loose while trying to avoid getting swept in the first round for the second time in franchise history. Typically buttoned-down coach Mike Sullivan cracked a joke after Tuesday's morning skate and did little to tinker with his lineup, adamant Pittsburgh could pick itself up off the mat if it got back to — as Sullivan so often puts it — "playing the right way."
The team that began the playoffs with hopes of capturing its third Stanley Cup in four years looked ready to bounce back. For a couple of minutes anyway.
Guentzel found space in the slot and ripped a shot past Lehner 35 seconds into the game for the first goal of the series by Pittsburgh's top line. The 574th consecutive home sellout crowd buzzed. The Penguins had the momentum and the lead.
Just as they did at every critical point during what became a lopsided series, the Islanders responded almost immediately.
Penguins defenceman Kris Letang whiffed while trying to pinch into the New York zone, creating a 2-on-1 the other way that Eberle finished to even it at 1 just 1:34 after Guentzel had put Pittsburgh in front.
The goal seemed to steady the Islanders, who settled in and kept it simple. New York posted the franchise's best regular-season record in 35 years by limiting chances and relying heavily on Trotz's system that preaches pragmatism and patience.
The Islanders weathered Pittsburgh's early push and went ahead with 1:54 to go in the first period when Nelson slipped behind Penguins forward Garrett Wilson and darted to the net. Bailey's pass from the below the goal line arrived right as Nelson flashed in front of Pittsburgh goaltender Matt Murray. Nelson flicked a shot over Murray's right pad, and New York was back in control.
Another stellar defensive effort and a little bit of puck luck helped. Crosby hit the inside of the left post in the middle of the second period, and Islanders defenceman Scott Mayfield bailed out Lehner by making a save with his left leg on a point-blank shot by Phil Kessel early in the third.
And that was it. When Bailey's flip went the length of the ice and into the empty net, the Islanders' bench erupted and the Penguins trudged toward an off-season that could lead to significant changes.
NOTES: Crosby's assist on Guentzel's goal moved him past Hall of Famer Steve Yzerman and into 10th place on the NHL's all-time playoff points list (186). … Pittsburgh went 0 for 3 on the power play and finished 1 for 11 in the series with the man advantage. … The Islanders were 0 for 3 on the power play. … Lehner stopped 135 of the 141 shots he faced in the series. … Murray finished with 23 saves.
More AP NHL: https://apnews.com/NHL and https://twitter.com/AP_Sports
Will Graves, The Associated Press


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Breaking Qualcomm up is not the best way to turn its performance around, the company's board has decided.
Qualcomm designs and makes chips, primarily for the booming smartphone and connected devices markets. But in July the company reported lackluster results for the three months to June 28, with a 14 percent year-on-year decline in revenue and 47 percent drop in net profit.
CEO Steve Mollenkopf said then that he planned on "right-sizing" the company's cost structure — a phrase that turned out to mean laying off more than one employee in seven. He also engaged external advisors to review the company's corporate structure and look at whether splitting the company up would increase its value.
But on Tuesday Qualcomm announced that it planned to keep its chip design and manufacturing operations together, concluding that its current structure puts it in the best position to make profitable products in the long term.
Mollenkopf faces a tough time turning that existing corporate structure around, as revenue and profit have continued to fall since he began the review. The year-on-year revenue decline accelerated to 18 percent for the three months to Sept. 27, although the drop in net profit slowed slightly, to 44 percent, Qualcomm reported on Nov. 4.
Looking ahead to the next quarter, Qualcomm warns that the revenue decline could accelerate further, with a year-on-year drop of between 15 percent and 27 percent, although it expects the fall in profit to slow to 23 percent or less, thanks in part to its cost-cutting program.
Qualcomm's rejection of a corporate split comes after Hewlett-Packard agreed to break up Dave and Bill's legacy, splitting a few weeks ago into Hewlett Packard Enterprise and HP Inc. The day that breakup happened, shareholders did see an increase in value, with the 1.6 percent drop in HPE's share price more than offset by the 13 percent jump in that of HP, defying the conventional wisdom that PCs and printers are on the way out.
Qualcomm, though, defended its existing structure on Tuesday, saying that it benefits twice from its in-house research and development operations, which create new technologies it can license as well as allowing it to improve the products it sells.
The components for smartphones and for the Internet of Things that Qualcomm designs are licensed to other companies for incorporation in their own chipsets. That business model is common in the chip industry — Qualcomm licenses the processor cores it uses in its designs from ARM, which does not make chips itself.
Qualcomm, though, does makes its own chips, competing with some of its customers. That approach allows it to push its own technologies in the smartphone industry, encouraging other chipmakers to adopt and license them, it said.