Lung Cell Biology is sponsored by NIH NHLBI. Supports experimental approaches to investigate lung cellular function and dysfunction.

Expired RFA-HL-09-004: NHLBI Progenitor Cell Biology Consortium Research Hubs (U01) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Participating Organizations Health (NIH), ( http://www.

nih. gov ) Components of Participating Organizations National Heart, Lung, and Blood Institute (NHLBI), ( http://www. nhlbi.

nih. gov ) Progenitor Cell Biology Consortium Research Hubs (U01) Update: The following update relating to this announcement has been issued: February 2, 2012 - See Notice NOT-HL-12-011. Notice of Funding Opportunity for Ancillary/Collaborative Studies for the NHLBI Progenitor Cell Biology Consortium.

March 28, 2011 - This RFA has been reissued as PA-11-186. February 8, 2011 - See Notice NOT-HL-11-123 Notice of Funding Opportunity for Ancillary/Collaborative Studies for the NHLBI Progenitor Cell Biology Consortium. May 7, 2010 - See Notice NOT-HL-10-109 Notice of Funding Opportunity for a Cell Characterization Core for the NHLBI Progenitor Cell Biology Consortium .

For Applications (RFA) Number: RFA-HL-09-004 Federal Domestic Assistance Number(s) Letters of Intent Receipt Date(s): April 1, 2009 Council Review Date: August Anticipated Start Date: September 30, 2009 Additional Information To Be Available Date (URL Activation Date): January 12, 2009 Additional Overview Content National Heart, Lung, and Blood Institute (NHLBI) invites applications to participate in the NHLBI Progenitor Cell Biology Consortium.

The goal of the Consortium is to identify and characterize progenitor cell lineages, to direct the differentiation of stem and progenitor cells to desired cell fates, and to develop new strategies to address the unique challenges presented by the transplantation of these cells.

The Consortium will assemble clusters of synergistic research projects, each with a multi-disciplinary team of Principal Investigators, to establish virtual Research Hubs focused on progenitor cell biology. The Consortium will also contain core research support facilities and skills development components.

Hub applications must consist of a cluster of two to four synergistic applications, each of which must derive from a separate R03 application funded through RFA-HL-08-012 . One of the applications must be designated the Lead PI/PD application. Mechanism of Support.

This FOA will utilize the Research Project Cooperative Agreement (U01) mechanism of support . Funds Available and Anticipated Number intends to commit approximately $10 million total costs for FY2009. The total amount to be awarded for the Consortium will be a maximum of $70 million total costs for the seven-year project period.

It is anticipated that 6 Research Hub awards will be made through this FOA. Additional funds will be available through a separate FOA to fund an Administrative Coordinating Center, cores and pilot projects to be administered by the ACC ( http://grants. nih.

gov/grants/guide/rfa-files/RFA-HL-09-005. html ). The total project period for an application submitted in response to this FOA is 7 years.

Maximum allowable direct costs are $750,000 per year for each U01 application in the Hub. Institutions/Organizations. Institutions/organizations listed in Section III, 1.

A. are eligible to Eligible Project Directors/Principal Investigators (PDs/PIs). TO BE ELIGIBLE TO APPLY TO THIS FOA, PDs/PIs MUST HAVE BEEN PART OF AN R03 AWARD IN RESPONSE TO FOA HL-08-012 ( http://grants.

nih. gov/grants/guide/rfa-files/RFA-HL-08-012. html ), AND MUST ALSO HAVE PARTICIPATED IN THE DECEMBER 15, 2008, GRANTEES MEETING IN BETHESDA, MARYLAND.

Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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 Number of Applications.

Applicants may submit only one application as PI/PD; participation in additional applications as co-investigator is permitted provided they are scientifically distinct.

Only one Lead PI /PD application, and only two U01 applications in total, may be derived from any R03 application (i.e. one Lead PI/PD application and one non-Lead, or two non-Lead PI/PD applications Applicants to this FOA may not be part of an application to the Consortium Administrative Coordinating Center ( http://grants. nih. gov/grants/guide/rfa-files/RFA-HL-09-005.

html ). Resubmissions. Resubmission applications are not permitted in response to this FOA.

applications are not permitted in response to this FOA . Date(s). This FOA uses non-standard due dates.

See Receipt, Review and Anticipated Start Dates . Additional Information To Be Available at http://www. nhlbi.

nih. gov/funding/inits/faq-progenitor. htm Application Materials.

See Section IV. 1 for application materials. Hearing Impaired.

Telecommunications for the hearing impaired are available at: TTY 301-451-5936. Part II Full Text of Announcement Section I. Funding Opportunity Section II.

Award Information 1. Mechanism(s) of Support 2. Cost Sharing or Matching 3.

Other - Special Eligibility Criteria Section IV. Application and 1. Address to Request Application Information 2.

Content and Form of Application Submission 3. Submission Dates and Times B. Sending an Application to C.

Application Processing D. Application Assignment 4. Intergovernmental Review 6.

Other Submission Requirements and Information Section V. Application Review 2. Review and Selection Process A.

Additional Review Criteria C. Resource Sharing Plan(s) 3. Anticipated Announcement and Award Dates Section VI.

Award Administration 2. Administrative and National Policy Requirements Terms and Conditions of Award Investigator Rights and Responsibilities Collaborative Responsibilities Section VII. Agency Contact(s) 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 Lung, and Blood Institute (NHLBI) invites applications to participate in the NHLBI Progenitor Cell Biology Consortium.

The goal of the Consortium is to identify and characterize progenitor cell lineages, to direct the differentiation of stem and progenitor cells to desired cell fates, and to develop new strategies to address the unique challenges presented by the transplantation of these cells.

The Consortium will assemble clusters of synergistic research projects, each with a multi-disciplinary team of Principal Investigators, to establish virtual Research Hubs focused on progenitor cell biology.

The Consortium will also contain core research support facilities and skills development At present, a number of promising discoveries, technologies, and reagents are poised to have a catalytic effect on the field of regenerative biology and medicine.

The aim of this initiative is to markedly accelerate progress by forming a coordinated Consortium that includes leading scientists in the field of cardiovascular, pulmonary and hematopoietic cell biology, working closely with experts in the general field of progenitor cell biology.

Additional expertise in areas such as immunology, developmental biology, bioengineering, animal model development, and imaging will also be required to develop and translate these technologies. The goal of the Consortium will be to harness advances in stem cell and progenitor cell biology to improve the understanding and treatment of cardiovascular, lung, and blood diseases.

Areas of emphasis are expected to include lineages derived from murine, human, and other embryonic stem cells, progenitor cells, somatic stem cells, and induced pluripotent stem (iPS) cells (somatic cells reprogrammed to become pluripotent), which are all included in the progenitor cell biology Consortium described in this FOA.

In addition, the derivation of iPS cells from patients with genetic diseases, and differentiation of these cells to specific cell types, is expected to give unique mechanistic insight into disease processes. The development of allogeneic cell lines offers the promise of faster, simpler, and cheaper regenerative therapies, but brings new challenges in understanding immune tolerance and therapy to prevent rejection.

The generation of publicly available molecular, epigenetic, and functional databases on specific embryonic stem cell lines, induced pluripotent cells, and progenitor lineages will also be a priority.

Participants in the Consortium will be expected to share data and resources with the Consortium rapidly in order to promote the goals of The research emphasis within the Consortium will vary depending upon the status of stem and progenitor cell science.

NHLBI recognizes that fundamental knowledge of cardiovascular and pulmonary stem and progenitor cell biology, including progenitor cell lineages, lags behind the level of understanding in the hematopoietic field.

Therefore, an area of emphasis is the generation of well-characterized cardiovascular and lung progenitor cell fate maps, integrated with specific approaches to identify, purify, renew, and direct the differentiation of specific lineages of interest.

Another important focus will be regional and/or developmental differences in cell origin and lineage, for example proximal versus distal lung versus upper respiratory tract, and the identification of appropriate phenotypic markers to facilitate these studies. For hematopoietic studies, the de novo generation of hematopoietic stem cells (HSC) will be a key objective, taking advantage of established stem cell markers, models and reagents.

Accomplishment of this goal has clear clinical implications given the uses of HSC for transplantation. The combination of cardiovascular, pulmonary, and hematopoietic cell biology within the Consortium is seen as a clear advantage anticipated to accelerate progress in all three areas.

The Consortium is expected to foster innovative new technologies, reagents, strategies, and protocols that will have a major impact on scientific, translational, and clinical utility of cardiovascular, lung, and hematopoietic progenitor cell lineages.

Selected research examples include, but are not limited Reprogram human and mouse somatic cells to embryonic stem cells and/or specific pulmonary, cardiac, vascular, and hematopoietic lineages of scientific, translational, or clinical interest.

Derive induced pluripotent stem (iPS) cells from patients with unique genotypes to permit differentiation to hematopoietic, pulmonary, and cardiovascular cell types of interest for characterization of disease mechanisms and to identify molecular inducers that correct genetic networks. Develop new technologies to bypass the use of oncogenes for reprogramming and avoid retroviral vectors carrying the risk of insertional mutagenesis.

Examples of alternative strategies may include transient gene expression vectors and engineered membrane-permeable transcription factor proteins or small molecules.

Develop new strategies to address the unique challenges presented by the transplantation of allogeneic progenitor cells, including approaches to deal with cell rejection, immune surveillance and tolerance, cell survival, matrix interactions, and integrated/functional grafting.

Identify, trace, purify, renew, and direct differentiation of specific lung, cardiac, and vascular progenitor lineages with state of the art technology from mouse and human sources.

Generate new, improved strategies for creating gene targeting in human ES cells with enabling human ES cell derived progenitor Determine the genetic and epigenetic state of iPS cells and define the network of genes (1) maintaining pluripotent stem cells in an undifferentiated state; (2) regulating development of stem and progenitor cells from pluripotent stem cells, e.g., iPS cells; and (3) maintaining the stem or progenitor cells population.

Characterize and compare specific heart, lung, and blood stem or progenitor cells from mouse and human sources by transcriptional, FACS, epigenetic, and functional analysis, with a particular interest in novel approaches for functional evaluation employing tools of nanotechnology, bioengineering, and tissue engineering.

Convert pluripotent stem cells, e.g. iPS, to hematopoietic stem cells de novo and compare in transplant models to normal bone marrow-derived HSC cells and to cells derived from other The goal of this FOA is to develop a highly interactive and synergistic Consortium of investigators who will share ideas, data and resources to move the field of progenitor cell biology forward.

The Consortium will consist of virtual Research Hubs formed from clusters of synergistic research projects funded through this FOA, and an Administrative Coordinating Center (ACC) supporting the Consortium funded through a separate FOA, http://grants. nih. gov/grants/guide/rfa-files/RFA-HL-09-005.

html . The ACC will also administer funds to support cores, pilot studies, and ancillary and collaborative studies. To foster new collaborations and facilitate partnerships among different disciplines, applications will be submitted as two to four clustered grant applications, each derived from separate R03 applications submitted in response to FOA RFA-HL-08-012 .

Within each cluster, a lead PI/PD must be identified who will be the point of contact and will represent the Hub to NHLBI staff. PI/PDs of other application(s) in the cluster will be collaborating PI/PDs. A minimum of 3 calendar months effort is required for the lead PI/PD, and a minimum 2.

4 calendar months effort is required for the PI/PDs of the collaborating grants The Hub of applications must clearly describe the management of the collaborative research. To ensure this, they must include a management plan and identify a scientific oversight committee.

The management Outline plans and mechanisms to keep the project Set intermediate milestones on a timeline to allow for the evaluation of progress towards the project's goal.

Explain how collaborators can be added or removed as the expertise, knowledge, and skills necessary to advance the project Describe how intellectual property issues will be Each Hub of applications must identify a scientific oversight committee, consisting of those individuals identified in the management plan, who together would have the intellectual and leadership responsibilities for the collaborative research project normally attributed to the PI/PD.

At a minimum, the oversight committee must have a representative from each collaborating application in the Hub. Funds should be budgeted for administering the scientific oversight committee and activities noted in the management plan. The Consortium will consist of multiple clusters of applications, each forming a virtual Research Hub.

In addition to interactions within Research Hubs, extensive collaboration between Hubs is expected. The Consortium will be supported by an ACC to provide logistical support to the Consortium activities.

ACC : The ACC will serve a range of functions such as organizing meetings; arranging teleconference calls of the Steering Committee, External Advisory Committee, and Consortium annual meeting; and designing and maintaining written materials and websites to support the Consortium. The ACC will be responsible for solicitation of applications for cores, pilot studies, and collaborative and ancillary studies.

The ACC will oversee the review and award of pilot/ancillary study funds for the Consortium, award subcontracts for Cores, and coordinate the submission of progress reports by the awardees for review by the External Advisory Committee and NHLBI staff. The ACC will also coordinate skills development activities .

Cores : Cores, such as a cell processing core, or an imaging core, will provide resources and services to multiple Research Hubs. Requirements for Cores in the Consortium will be evaluated once the Consortium has been established. The NHLBI, with input from the External Advisory Committee, will determine the Core configuration, and the ACC will allocate funds accordingly.

Cores will initially be funded for two years, and may be phased in and out based on scientific need during the course of the major goal of the NHLBI Progenitor Cell Consortium is to foster highly innovative, high-risk approaches that are not easily funded by traditional mechanisms and that have the potential for unusually high impact to significantly advance the field.

Hence, pilot studies will be supported for a maximum of two years at $100,000 direct costs per year. Solicitations for pilot studies will be initiated beginning in Year 2 by the ACC. Pilot studies that bridge between two or more Consortium Research Hubs will be given higher priority in order to enhance the development of synergies between Consortium investigators.

The pilot studies are also expected to be helpful in developing young investigators. The External Advisory Committee will be responsible for peer review of these new pilot studies. Progress on these studies will be monitored by program staff.

and Collaborative Studies : As the resources and programs develop, it is anticipated that new opportunities will arise that will need additional expertise from outside the Consortium or require new collaborations with other members of the Consortium. To meet this need, funds will be made available through the ACC to fund ancillary and collaborative studies awards.

Solicitations for ancillary and collaborative studies will be initiated by the ACC beginning in Year 2 of funding. Expedited peer review by the External Advisory Committee will be used to facilitate flexibility and rapid funding of ancillary studies. Progress on these studies will be monitored by NHLBI staff.

Committee : The Consortium will have a Steering Committee that will be responsible for overall scientific direction, coordination and oversight. The Steering Committee will be composed of the Lead PIs for each Research Hub, the ACC PI, and the NHLBI Project Scientist. The Steering Committee will be chaired by an investigator selected by the NHLBI.

The Steering Committee will meet in person for an implementation meeting at the start of the project period, by conference call at least quarterly, and in person at least twice a year throughout the project Development Committee : A Skills Development Committee, composed of an investigator from each Research Hub and from the ACC, will develop and coordinate activities between the Research Hubs to enhance skills development for graduate students, postdoctoral fellows, and young faculty.

Each application should identify a Skills Development Coordinator, whose relevant experience is well documented in the Research Plan. Skills development activities will be developed across the Consortium after funding, and do not need to be specified Advisory Committee: An External Advisory Committee (EAC) will oversee the Consortium.

The Committee will consist of non-Consortium affiliated scientists and other experts appointed by the NHLBI to provide annual reviews of progress, and serve as the peer review panel for pilot studies, ancillary and collaborative Support for Skills Development: Full implementation of a nationwide effort in progenitor cell research requires the availability of MD, MD/PhD, and PhD scientists capable of independent research careers and equipped with the leading experimental strategies and techniques to address the outstanding questions in the field.

Hence, a unique feature of the Consortium is to support and develop promising new researchers with advanced skills required to conduct research using state-of-the-art technologies and approaches. These can be investigators beginning their research careers or established investigators who are new to the application of the relevant disciplines to the mission areas of the NHLBI.

Applicants should budget into their applications support for investigator skills development to be supported by the Consortium for up to 2 years, during which time it will be expected that the supported investigator will apply for NIH training or research grants to continue supporting the research initiated through the Consortium.

In this way, Consortium funds will be available for additional new investigators on a continuous basis to optimize the number of MD, MD/PhD, and PhD scientists developed by the program.

Supported investigators will be encouraged to rotate through different laboratories in order to learn new skills, and to facilitate this process each application should identify a Skills Development Annual Grantee Meeting : Upon initiation of the program, the ACC on behalf of the NHLBI will arrange annual meetings to encourage the exchange of information among the investigators who participate in this program.

In the preparation of the budget for the grant application, applicants should include travel funds for one meeting each year to be held in or near Bethesda, MD, for the Principal Investigators and key collaborators. At these meetings awardees will be expected to share their results and to help evaluate the progress of the Centers.

Attendance at these meetings is Information - Required Federal Citations , for policies related to this announcement. Section II. Award Information opportunity will use the Research Project Cooperative Agreement (U01) award mechanism(s).

In the cooperative agreement mechanism, the Project Director/Principal Investigator (PI/PD) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements , "Cooperative Agreement Terms and Conditions of Award."

This is a one-time solicitation to fund the Progenitor Cell Biology Consortium Administrative Coordinating Center for seven years. The Consortium will undergo a mid-course review by the External Advisory Committee during the fourth year of funding to determine how well the Consortium is meeting its goals.

Continued funding for individual progenitor cell biology research projects funded through this FOA, and for the ACC funded through FOA http://grants. nih. gov/grants/guide/rfa-files/RFA-HL-09-005.

html , will be contingent on the outcomes of this review. Metrics to be assessed in the review of the research projects will include how well they are achieving the milestones proposed in the research plan, productivity, contributions to the overall goals of the Consortium, and data sharing.

Continuation of this program at the end of the seven years will depend on evaluations conducted by the External Advisory Committee, NHLBI strategic priorities, and available FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants. nih.

gov/grants/funding/phs398/phs398. html ). funds available for support of 6 Research Hubs awarded as a result of this announcement is $ 10 million for fiscal year 20 09 .

Future year amounts will depend on annual appropriations. total amount of funding that the NHLBI expects to award through this announcement is $70 million for a project period of seven years.

expected direct cost amount for the Consortium awards will be up to $750,000 will also administer a budget for shared consortium cores, ancillary and collaborative studies, and pilot studies funded through the Consortium ACC 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 the receipt of a sufficient number of meritorious Facilities and administrative costs requested by Consortium participants are not included in the direct cost limitation; see NOT-OD-05-004 .

grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in Section III.

Eligibility Information The following organizations/institutions are eligible Public/State Controlled Institutions of Private Institutions of Higher Education Black Colleges and Universities (HBCUs) Controlled Colleges and Universities (TCCUs) Alaska Native and Native Hawaiian Serving Institutions Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Agencies of the Federal Government 1.

B. Eligible Individuals individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PI/PD is invited to work with his/her institution 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.

program does not require cost sharing as defined in the current NIH Grants Policy Statement . Other-Special Eligibility Criteria are not permitted to submit a resubmission application in response to this FOA. Renewal applications are not permitted in TO BE ELIGIBLE TO APPLY TO THIS FOA, PDs/PIs MUST HAVE BEEN PRINCIPAL INVESTIGATOR OR CO-INVESTIGATOR ON AN R03 AWARD FUNDED IN RESPONSE TO FOA HL-08-012 ( http://grants.

nih. gov/grants/guide/rfa-files/RFA-HL-08-012. html ), AND MUST ALSO HAVE PARTICIPATED IN THE DECEMBER 15, 2008, GRANTEES MEETING IN Investigators may submit only one application as PI/PD; participation in additional applications as co-investigator is permitted provided they are scientifically distinct.

Only one Lead PI /PD application, and only two U01 applications in total, may be derived from any R03 application (i.e. one Lead PI/PD application and one non-Lead, or two non-Lead PI/PD applications. Applicants to this FOA may not be part of an application to the Consortium Administrative Coordinating Center ( http://grants. nih.

gov/grants/guide/rfa-files/RFA-HL-09-005. html ). Multiple applications may be submitted from a Section IV.

Application and Submission 1. Address to Request Application application instructions are available at http://grants. nih.

gov/grants/funding/phs398/phs398. html in an interactive format. Applicants must use the currently approved version of the PHS 398.

For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected] . Telecommunications for the hearing impaired: TTY and Form of Application Submission must be prepared using the most current PHS 398 research grant application instructions and forms.

Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www. dnb.

com/us/ . The D&B number should be entered on line 11 of the face page of the PHS 398 form. The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form, and the is available in the PHS 398 grant application instructions .

3. Submission Dates and Times received on or before the receipt date described below ( Section IV. 3.

A ). Submission times N/A.

Letters of Intent Receipt Date: April 1, 2009 Application Receipt Date: May 1, 2009 Peer Review Date: July-August 2009 Council Review Date: August 2009 Anticipated Start Date: September applicants are asked to submit a letter of intent that includes the following Descriptive title of proposed research Name, address, and telephone number of the Principal Investigator Names of other key personnel Participating institutions Number and title of this funding 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 letter of intent should be sent to: National Heart, Lung, and Blood Institute National Institutes of Health 6701 Rockledge Drive, Room 7214 Bethesda, MD 20817 (express/courier service) Sending an Application to the NIH must be prepared using the forms found in the PHS 398 instructions for preparing a research grant application.

Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to: Center for Scientific Review National Institutes of Health 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 (U.S. Postal Service Express Bethesda, MD 20817 (for express/courier service; deliveries of applications are no longer permitted (see http://grants. nih.

gov/grants/guide/notice-files/NOT-OD-03-040. html ). submission, two additional copies of the application and all copies of the appendix material must be sent to: National Heart, Lung, and Blood Institute National Institutes of Health 6701 Rockledge Drive, Room 7214 Bethesda, MD 20817 (express/courier service) on or before the application receipt date) described above ( Section IV.

3. A. ).

If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute incomplete and/or non-responsive applications will not be reviewed.

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. status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons. era.

nih. gov/commons/ . This initiative is not subject to intergovernmental are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The Grants Policy Statement can be found at NIH Grants 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 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 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 NIH Grants Policy Statement http://grants. nih. gov/grants/policy/nihgps_2003/NIHGPS_Part6.

htm ). Submission Requirements and Information for preparation of a Hub (cluster) of applications applications in a Hub must share identical titles and must refer to the lead PI/PD s application in the cover letter. The Research Plan sections for each of the individual applications in the Hub will describe the research project or related projects to be carried out by that component of the Hub.

The Research Plan section for the lead PI/PD application will additionally describe the overall goals of the Research Hub in the context of their vision for the Consortium, and the synergistic integration of research throughout the Research Hub.

The review of the application will evaluate the entire project as a whole, the strength of the collaborating component projects, and the synergy between the Hub The organization of the application will be as described in the PHS 398 application instructions (see http://grants. nih. gov/grants/funding/phs398/phs398.

html ). The Research Design and Methods section for each component application of the Hub should propose a project or group of related projects consistent with the objectives of the FOA and interrelated with the other applications in the Hub that can be completed by the investigators in the Hub component in seven years.

Page limits will allow up to a total of 20 pages for the Specific Aims, Background and Significance, Preliminary Studies, and Research Design and In addition, the Background and Significance section for the application from the Lead PI for the Hub of applications will include an additional section labeled Research Hub Plan, for which up to an additional 10 pages can be used.

This section will include a discussion of the research team’s views of the important questions facing the field of progenitor cell biology and its application to heart, lung and/or blood diseases, and explain how their proposed research addresses one or more of these questions.

The interactions between the individual component applications of the Hub, and the synergies provided by the formation of a Research Hub through this cluster of applications, should be clearly identified. The Research Hub Plan in the Lead PI s application must clearly describe the management