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Centers of Excellence in Translational Human Stem Cell Research
Part I Overview Information
RFA Number: RFA-NS-05-005
Components of Participating Organizations:
National Institute of Neurological Disorders and Stroke (NINDS), (http://www.ninds.nih.gov)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), (http://www.niddk.nih.gov)
National Heart, Lung, and Blood
Institute (NHLBI), (http://www.nhlbi.nih.gov)
Announcement Type:
New
Update: The following update relating to this announcement has been issued:
Key Dates
Release Date: September 29, 2004
Pre-Application Meeting Date: December 10, 2004
Letters Of Intent Receipt Date(s): February 24, 2005
Application Receipt Dates(s): March 24, 2005
Peer Review Date(s): June/July, 2005
Council Review Date(s): September, 2005
Earliest Anticipated Start Date: September, 2005
Expiration Date: March, 25, 2005
Due Dates for E.O. 12372
Not Applicable
Executive Summary
The National Institutes of Health (NIH) invite applications for specialized Centers to accelerate application of the latest advances in human stem cell biology for the development of novel diagnostic or therapeutic uses, and of preclinical studies employing human stem cells in animal models of disease. The P50 mechanism will be used to create three Centers of Excellence in Translational Human Stem Cell Research. These centers will bring together basic stem cell biologists, researchers and clinicians with disease-specific expertise, physicians and surgeons skilled in novel modes of cell delivery, and investigators experienced in developing and assessing animal models of human diseases to create new research teams, and to conduct hitherto-unexplored projects such as preclinical studies for cell-based therapy. This initiative targets critical gaps in research that are delaying the conversion of new discoveries to new therapies, and particularly encourages the formation of new, multidisciplinary teams involving scientists that may not have worked in the human stem cell field and those that incorporate the full spectrum of expertise and experience in translational medical research. We anticipate that such research will ultimately lead to innovative approaches for the prevention, treatment, and cure of disease, and accelerate the translation of basic scientific discoveries in the laboratory to new treatments for patients. The NIH intends to commit up to $4.5 million dollars in FY 2005 to fund three new Centers. Eligible organizations include domestic public or private institutions. There is no limit on the number of applications from an institution or individual. Any individual with the skills, knowledge and resources necessary to carry out the proposed research is invited to work with the institution to develop and application for support. Individuals from underrepresented or disadvantaged groups are always encouraged to apply for NIH programs. The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact Grantsinfo, Telephone (301) 710-0267, Email: Grantsinfo@nih.gov .
Telecommunications for the hearing impaired: TTY 301 451-5936.
Table of ContentsThis Request for Applications (RFA) supports the establishment of three Centers of Excellence in Translational Human Stem Cell Research to accelerate application of the latest advances in human stem cell biology for the development of novel diagnostic or therapeutic uses, and of preclinical studies employing human stem cells and animal models of disease. Recent findings provide new and unprecedented opportunities for therapeutic applications of embryonic and adult stem cells, progenitors, and differentiated cells derived from these sources in treatment strategies for a host of devastating diseases. These centers will bring together basic stem cell biologists, researchers and clinicians with disease-specific expertise, physicians and surgeons skilled in novel modes of cell delivery, and investigators experienced in developing and assessing animal models of human diseases to create new interdisciplinary research teams, and to conduct hitherto-unexplored projects such as preclinical studies for cell-based therapy. Formation of new multidisciplinary research teams involving scientists that may not have worked in the human stem cell field and those that incorporate the full spectrum of expertise and experience in translational medical research are particularly encouraged. This initiative targets critical gaps in research that are delaying the conversion of new discoveries to new therapies. Research on some disease areas will require more extensive basic research on stem cell biology than other areas; therefore, across these areas of research, the research gaps are located at different points within the discovery process. While applications must target a research "gap", it is expected that applications will vary in the timelines proposed for the progression of translational studies. We anticipate that such research will ultimately lead to innovative approaches for the prevention, treatment, and cure of disease, and accelerate the translation of basic scientific discoveries in the laboratory to new treatments for patients.
RESEARCH OBJECTIVES
In regenerative medicine the ultimate goal is to replace, repair and regenerate cells, tissues and organs in order to restore vital biological function(s) halted or compromised by age, injury or disease. Because stem and progenitor cells have the potential to replace cells that are dysfunctional or lost, stem cell research offers the promise of curing disease and ending disabilities. Recent advances in the understanding of stem and progenitor cell biology, transplantation of autologous and allogeneic cells for the treatment of disease, the development of cellular and molecular imaging tools, and the management of immune function after stem cell transplantation offer potential novel approaches to clinical problems in a variety of congenital, developmental, trauma-related, or degenerative diseases. Fulfilling this promise requires harnessing the activities of exogenous and/or endogenous stem cell populations in the host environment, perhaps in combination with biomolecules and biomaterials, and integrating them into host tissue. In addition to cell replacement therapy, the ability to selectively produce one or more differentiated cell types at will from pluripotent human stem cells would be of tremendous clinical importance in investigating the effects of drugs, environmental and genetic factors on differentiation and cell function in human tissue and organ systems. These approaches could aid in drug discovery and ultimately in the development of a variety of effective treatment strategies.
There are, however, serious barriers to progress in realizing the potential of human stem cells in regenerative medicine. There are currently few markers, antibodies or probes with which to distinguish specific classes of stem or progenitor cells, to follow their differentiation, or to facilitate their isolation. Similarly, there is little characterization of the niches within the host that allow regeneration, including the cell types and molecular cues that are responsible for tissue organization. While methods exist to allow lineage tracing in animal models, there are no well-defined, non-invasive methods and reagents with which to study the survival, migration, fate and function of stem cells and their progeny in the living animal or human. This limitation makes it difficult to investigate how stem or progenitor cells might behave differently in healthy and diseased states in vivo. The flexibility or plasticity of stem cells, coupled with their ability to self-renew, raises the specter of unintended side effects such as the formation of tumors or maladaptive neural circuits. Little is currently known about the frequency or circumstances under which these events occur, or how they could be controlled. We also need to learn how to avoid host rejection of grafted cells and more in general about how the host integrates the graft. Finally, coaxing cells to form functional tissue may require physical support, such as a three dimensional scaffold, in conjunction with chemical and mechanical signals, provided at appropriate times and places, to establish the intricate structures that characterize native tissue. While there is some work using artificial matrices, there is a need to expand this research with new types and designs of biomaterials. This may require an approach that combines bioengineering, stem cell biology and expertise in extracellular matrices.
Stem or progenitor cells can be obtained from a variety of tissues and from hosts of different ages; however, the requirements and potential for differentiation of each type of stem cell appear to be unique. Full realization of the potential for human cellular therapy ultimately will require understanding the fundamental properties of all classes of human stem cells. A key element in therapy development and translational research is the testing and comparison of the behavior of specific stem cells or their derivatives in animal models of diseases. Other innovative approaches include autologous cell therapies, such as exploring and exploiting the non-homologous use of stem and progenitor cells from novel, autologous sources. Finally, safe treatments can be realized only if preclinical and clinical research programs are designed to assess and avoid the possibility of host rejection, tumor formation and other adverse events.
It is clear that no single investigator, laboratory or discipline has the technical or physical resources to tackle the complex questions discussed above. The solution lies in developing synergy between the various scientific disciplines and investigators with very different expertise and resources. New therapies must/will be developed through the organized efforts of expert teams of scientists and clinicians combining the unique and complementary expertise of different disciplines, techniques, model systems or tissues and perhaps even different diseases. Our ultimate goal is to establish the optimal conditions and parameters (such as cell type, protocols, animal models and assessment tools) necessary for safe and efficacious use of stem cells in specific disease models that will translate into FDA-ready clinical studies and trials.
This new initiative reflects the desire of the National Institutes of Health (NIH) to support the development of new cellular therapies by integrating advances in basic research and translational opportunities. It is designed to encourage and enable basic and clinical investigators to collaboratively transform hypotheses into clinical applications through focused preclinical studies. Cellular repair strategies can include (1) therapies that prompt the body to regenerate damaged tissue, (2) tissue engineering techniques for the development of replacement tissue, and (3) direct transplantation of cells or tissues derived from stem or progenitor cells into damaged environments. Preclinical studies can also include rigorous testing and direct comparison of human stem, progenitor and differentiated cells derived from different sources in well-established models of human diseases. Others include controlled studies to monitor and establish the route of cell delivery, cell dosage and the use of appropriate controls.
Organization of the Centers of Excellence in Translational Human Stem Cell Research
The primary objective of this program is to foster novel collaborative research on heretofore unexplored but clinically relevant questions, enabling basic discoveries in human embryonic and adult stem cell biology to be rapidly applied to clinical problems. The NIH recognizes that the barriers to human stem cell therapies are different in each disease context and further, that applicants will accordingly develop a translational research program appropriate to, and possibly unique to, their therapeutic objectives.
Centers of Excellence in Translational Human Stem Cell Research would:
o Assemble interdisciplinary research teams made up of basic stem cell biologists, researchers and clinicians with disease-specific expertise, scientists with expertise in assessing immunogenicity and tolerance, physicians and surgeons skilled in novel modes of cell delivery, investigators experienced in developing and assessing animal models of disease, and experts in cell/tissue therapy product development;
o Target tightly focused projects that can only be implemented by multi-investigator collaborations working in a highly integrated and synergistic fashion;
o Be highly innovative in developing new concepts, methods, and technologies to substantially advance the state of the art in using human stem cells to approach a specific disease in humans through the use of appropriate animal models;
o Address critical issues that accelerate the application of stem cell science in therapeutic development, proposing solutions to obstacles that represent very substantial advances;
o Involve research that entails substantial risk, balanced by outstanding scientific opportunity and management plans that can deliver high potential payoff;
o Increase the pool of professional scientists with disease-specific expertise who work in stem cell biology;
o Target gaps and opportunities in research that are not currently funded by the NIH.
Research Topics
The goal of this new program is the translation of new findings in human stem cell biology to clinically relevant research for the ultimate purpose of developing new therapies for human disorders. Of particular interest are innovative collaborations in novel areas of stem cell research that could lead to new therapies, diagnostic products, or a key understanding and treatment of disease. Applications must demonstrate that the success of the proposed research requires the full collaboration between two or more independent groups contributing unique yet complementary expertise or resources. Centers are encouraged to undertake multi-disciplinary approaches, including preclinical projects that might lead toward clinical applications and clinical trials. In order to accomplish this goal, centers may consist of component parts/laboratories located in different institutions, and function as centers without walls. Funds may be allocated to support a small program of exploratory Pilot and Feasibility projects that integrate well with and fulfill the mission of the proposed preclinical projects and goals of the application. It is highly recommended that prospective applicants discuss possible applications with program staff to ensure that proposed projects are responsive to this program (see section Letter of Intent ).
The examples below illustrate areas of research where synergies between different disciplines or research topics meet the objectives of this program. These examples are not meant to be all-inclusive or restrictive, and it is not required that all or any of these topics be included. Applicants are encouraged to consider other innovative topics that are relevant to the goals of the new Centers of Excellence in Translational Human Stem Cell Research.
o Comparison of the mitotic potential and fates of different types of human, pluripotent, progenitor cells in vitro and in vivo including developing means to study and evaluate tumorigenic potential of stem cells or of their derivatives at different stages of differentiation;
o Investigation of the ability of different types of human stem cells, or of partially differentiated cells to revert to a more plastic, multipotent state, under normal conditions and following injury, disease or drug exposure;
o Identification of signals, signaling pathway components and transcriptional factors that regulate the fate(s) of transplanted human stem cells and their progeny following transplantation in the host;
o Development of markers and assays (in vitro and in vivo) that permit accurate and reliable characterization of the state of differentiation of human stem or precursor cells;
o Development of methods for identifying, isolating and enriching select human stem and precursor populations, intermediate states, and differentiated phenotypes. Starting cell sources could include: 1) stem cells from the adult tissues or organs, 2) stem or progenitor cells from fetal tissues or organs, or 3) human embryonic stem cells (NIH approved hESC lines only);
o Quantitative methods (genetic marking or imaging technology) to track the migration, differentiation, fate and function of human stem or progenitor cells and their derivatives in vitro and following transplantation in vivo;
o Quantitative studies (histological and behavioral) to assess the efficacy and function of cells derived from multiple sources of starting human stem/progenitor cells following transplantation in animal models of human disease or dysfunction. Assays could employ rodent models, as well as, non-human primate models, needed to not only address efficacy, but also safety prior to human transplantation;
o Comparison of the efficacy and risks of different modes of human stem cell delivery in large and small mammals, and in animals of different ages;
o Culture protocols that would support selectively the differentiation of human stem/progenitor cells into fully functioning phenotypes such as pancreatic islets or beta cells, neurons and glia, and cardiomyocytes;
o Identification and characterization of novel inducers of cell differentiation, replication, or proliferation, including the development of high throughput assays of chemical libraries;
o In vitro models to significantly increase endogenous stem cell replication/proliferation, including the identification of growth factors, extracellular components, or supporting cells that would enhance this process in the face autoimmune destruction;
o Studies to understand tissue/cell interactions and scaffold technology that can be applied to in vivo human cell-based therapy and in vitro grown tissues and organs including mechanisms of cell distribution and delivery and graft vascularization;
o Identification of genotype-phenotype correlations, modifier genes, pharmacologic manipulation, and genetic variation that influences therapeutic success of human cell-based therapy, as well as the incidence of adverse physiological events;
o Development of imaging and biomarker tools that can aid in the evaluation of clinical cell-based treatments;
o Studies to understand and evaluate the properties of stem cells or their derivatives that impact the establishment of tolerance to cellular transplantation;
o Identification of the effects of human stem cells on angiogenesis and the role of angiogenesis in stem cell engraftment.
Projects outside of the scope of this announcement
This initiative is not intended to fund mature areas of research such as studies that are already in clinical trials, or are currently being funded by the NIH. In addition, projects outside of the scope of this announcement include:
o studies on non-human stem or progenitor cells;
o studies that are not focused on translational research examples of translational research include development of cell-based therapies or diagnostic tools;
o studies that focus on the use of gene vectors or gene transfer methods rather than their use in developing a cell-based therapy;
o studies that use stem cells in established protocols rather than using cells for novel protocols to regenerate specific cellular lineages or organs;
o studies that focus on use of stem cells for general immune modulation rather than exploring the immunogenicity or establishing allogeneic tolerance to stem cells and their derivatives.
Section II. Award InformationThis funding opportunity will use the NIH Specialized Centers of Research (P50) award mechanism. As an applicant you will be solely responsible for planning, directing, and executing the proposed project.
P50 grants differ from traditional program project (P01) grants in that they are more complex and flexible in terms of the activities that can be supported. In addition to support for multidisciplinary research projects, support is also provided for pilot research projects, specialized resources, and shared core facilities. This RFA is a one-time solicitation. Future unsolicited, competing-continuation applications based on this project will compete with all investigator-initiated applications and will be reviewed according to the customary peer review procedures.
This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions ( http://grants1.nih.gov/grants/funding/phs398/phs398.html ). A detailed categorical budget for the Initial Budget Period and the Entire Proposed Period of Support is to be submitted with the application.
2. Funds AvailableThe participating Institutes and Centers intend to commit approximately $4,500,000 dollars in FY 2005 to fund three new and/or competitive continuation grants in response to this RFA. An applicant may request a project period of up to four years and a budget for direct costs up to $1 million dollars per year. See ( http://grants2.nih.gov/grants/guide/notice-files/NOT-OD-04-040.html ). Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. The earliest anticipated award date is September 2005.
If a grant application includes research activities that involve institutions other than the grantee institution, the application will be considered a consortium effort. Such applications are permitted, but it is imperative that the application be prepared so that the programmatic, fiscal, and administrative considerations are explained fully. The NIH published policy governing consortia is available http://grants1.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600251 (the applicable section is listed in the Table of Contents as CONSORTIUM AGREEMENTS ) and in the business offices of institutions that are eligible to receive Federal grants-in-aid and should be consulted before developing the application. For clarification of the policy, contact NIH staff listed identified in Questions about financial or grants management issues .
Applicants for these center grants should exercise great care in preserving the interactions of the participants and the integration of the consortium project(s) with those of the parent institution, because synergism and cohesiveness can be diminished when projects are located outside the group at the parent institution.
Section III. Eligibility InformationYou may submit (an) application(s) if your organization has any of the following characteristics:
Individual domestic institutions/organizations with both basic and preclinical research capabilities are eligible to apply. Inter-institutional collaborative research arrangements are also appropriate and encouraged. Coordination for such arrangements must be evident and clearly meaningful and appropriate for the research proposed. To be considered eligible, applicant organizations must have: (1) a statement of institutional commitment that addresses how the institution will incorporate the Center high within its institutional priorities; (2) research subprojects, representing a balance and diversity of basic and translational research approaches; (3) a qualified principal investigator who is a scientific leader in their field; (4) and appropriate shared resources to support the proposed research of the Center. A Center may also propose a program to develop Pilot and Feasibility projects that can be integrated into the translational research projects. Although an application must be submitted by a single applicant institution, subcontracted collaborative scientific arrangements with scientists from other institutions are encouraged if these arrangements are clearly delineated, and formally and officially confirmed by signed statements from the responsible officials of each institution. However, a full institutional commitment must come from the applicant institution.
1.B. Eligible IndividualsAny individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their 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 programs.
2. Cost SharingEach awarded Center must consist of two or more projects, all of which are directly related to the overall translational focus of the program . Component projects not located at the applicant institution must conform to NIH policies. Each component project, whether preclinical or basic, requires a well-described clinically relevant hypothesis, preliminary data, and a time-table for conducting the proposed investigations.
The overall project should include a scientific core and an Administrative Core that support the scientific projects of the P50. Core facilities are shared resources that enhance productivity or in other ways benefit a group of investigators working to accomplish the stated goals of the center. Cores should be designed to furnish investigators with a specific technique, service, determination, or instrumentation in a manner that will enhance the research in progress, consolidate manpower effort, and contribute to cost-effectiveness by providing a service at lower cost and possibly higher quality than if each investigator were to attempt the same activity individually. Cores may be proposed in relation to any acceptable research activity of the center, but usually fall into one of four categories: (l) provision of a technology that lends itself to automation or preparation in large batches; (2) complex instrumentation; (3) animal preparation and care; and (4) technical assistance and training.
Administrative Core: The Administrative Core should be responsible for 1) assisting in planning for the annual RFA Centers meeting (see below); 2) the overall coordination of the P50 project; and 3) overseeing the Center's Pilot and Feasibility Program if one is proposed. The Pilot and Feasibility Program may support one or more projects a year. These studies should complement and augment Center goals. This program could include plans to test and compare novel cell resources that were derived by investigators outside the P50. Given the rapid pace of research in stem cell biology, the program should explore novel technologies or concepts being developed outside the P50 in future years. Pilot and Feasibility studies should be well-coordinated and integrated with existing projects and Core activities.
Scientific Core: Examples of core activities include: 1) a culture facility that could grow human stem/progenitor cells and generate sources of differentiated cell phenotypes that would be used for cell replacement therapy, 2) a culture facility that would optimize for cell replication, proliferation and survival, and provide an abundant source of human cells for transplantation 3) a transplantation facility that would test the efficacy of these novel cell sources by quantitatively tracking transplanted cells and assessing their function in animal models of human disease, or 4) a facility for screening chemical inducers of human cell differentiation.
The organization and proposed mode of operation of each core should be described, with a plan for prioritizing investigator use of the core as well as the criteria for determining core users or potential users.
Teaching the investigators and/or their staff members' new techniques and methodologies may be an important function of the cores. The cores are not intended to supplant investigator capabilities; rather, they are intended to enhance the opportunities of investigators to learn and become proficient in the technologies available through the core.
Each Center must have a well-delineated organizational structure and administrative mechanism that foster interactions between investigators, accelerate the pace of research, enable translation of basic research findings to clinical applications, and ensure a productive research effort.
Annual RFA Centers Meeting: Upon initiation of the program, the NIH will arrange annual meetings to encourage the exchange of information among 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 Bethesda, Maryland. Applicants should also include a statement in the applications indicating their willingness to participate in such meetings.
Section IV. Application Submission Instructions1. Address to Request Application Information
The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov .
Telecommunications for the hearing impaired: TTY 301-451-5936.
2. Content and Form of Application Submission
Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). 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/ . 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 on line 2 of the face page of the application form and the YES box must be checked.
SUPPLEMENTARY INSTRUCTIONS FOR PREPARING AN APPLICATION
Use form PHS 398 ( http://grants.nih.gov/grants/funding/phs398/phs398.html ). Each budget unit (project or core) should be written in the style and within the page limitation described in the PHS 398 instruction kit. To aid in the review of these applications, the applicant should assemble the component units following the format described below.
Please note that each part of the application should be complete in itself, as different parts may be reviewed by different reviewers.
SECTION I - GENERAL INFORMATION FOR THE ENTIRE APPLICATION
A. FACE PAGE
This is Form Page 1 of the application; number succeeding pages consecutively.
Complete all items on the face page as directed. In the title block, item 1, put "Center of Excellence in Translational Human Stem Cell Research." Mark item 2 "yes" and write in the RFA code RFA-NS-05-005, as listed in the NIH Guide to Grants and Contracts, and "Centers of Excellence in Translational Human Stem Cell Research " for the title.
B. DESCRIPTION, PERFORMANCE SITES, AND KEY PERSONNEL
On Form Page 2, describe briefly the proposed program indicating the goals and objectives of the research projects and identify the purposes of the proposed cores. Do not exceed the space allowed. List key scientific and technical personnel participating in the Center. Use continuation pages as necessary, numbering consecutively.
C. TABLE OF CONTENTS
Adapt this page from PHS 398 Form Page 3 and provide a Table of Contents appropriate for the Center grant application, following these instructions. This should be paginated to follow the list of Key Personnel. Do not use letters (e.g., 4a, 4b, 4c, etc.). The Table of Contents should list all projects and cores for which funding is sought. Each project and core should be listed by the title and Principal Investigator. Specifically list the locations of the checklist and the various requested supporting documents, e.g., animal welfare assurances, and bibliographies.
D. BUDGET ESTIMATES
To aid in the review of your application, it is suggested that the forms found as pages 4 and 5 in PHS Form 398 be used for all budgets. Justify and document all costs for current and future years throughout. Prepare a series of composite Budget Tables for the Center as requested below.
1. Composite Budget
a. Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," to present the total direct cost budget for all requested support for the first year. For each category, such as "PERSONNEL," "EQUIPMENT," etc., list the amount requested for each research project and for each core unit.
If consortium arrangements have been made involving other institutions or organizations, include total costs (direct and facilities and administrative) associated with such third party participation in the "CONSORTIUM/CONTRACTUAL COSTS" category. Costs for purchased services should be itemized under "OTHER EXPENSES."
b. Use Form Page 5 "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," to prepare a budget, by category, that provides direct cost totals for each year of requested support.
E. BIOGRAPHICAL SKETCHES
Biographical sketches are required for all key scientific and technical personnel participating in the research projects and core units as listed on Form Page 2.
Beginning with the Center Director and Co-Director, and following in alphabetical order, submit biographical sketches as described in the "Instructions for Form PHS 398," using Form Page 6.
F. ENVIRONMENT AND RESOURCES
Complete a "RESOURCES" section for the overall Center. Briefly describe the features of the institutional environment that are or would be relevant to the effective implementation of the proposed program. As appropriate, describe available resources, such as clinical and laboratory facilities, participating and affiliated units, geographical distribution of space and personnel, and consultative resources. Include information on the support and commitment of the parent institution for the Center. Use continuation pages as needed. Include any supporting letters from the Institution.
G. CENTER LEADERSHIP AND ADMINISTRATION
This section should address the following:
Qualifications of the Center leadership. Describe the qualifications of the Center Director to lead the program, and that of the Co-Director to assist.
The proposed administrative structure. Include information on the support and commitment of the parent institution for the Center, the authority of the Director, the use of advisory committees (including any committees for the pilot and feasibility program), and the method of determining core access and space assignment. Describe an organizational framework, including lines of authority and sanction by appropriate institutional officials, and provide an organizational chart.
Purpose and Objectives of the Center. Discuss the philosophy and objectives of the Center and general plans for the proposed grant period. Discuss the composite research program, highlighting its central theme. List by title and investigator the component research projects and core units, showing the interrelationship between the research projects and the core units and their relationship to the central theme. Describe relevant history leading up to the Center application.
Collaborative Agreements. Any arrangements for collaborative and cooperative endeavors or subcontracting should be highlighted. Letters of Intent to Collaborate and Letters of Agreement from consultants should be referenced here and included at the end of the appropriate research project or core unit.
I. PRELIMINARY DATA PERTAINING TO THE WHOLE CENTER
This section should be used to present, in condensed form, previously published and/or preliminary data that are relevant to proposed Center activities and research projects that will be unique to the Center and will involve collaboration across projects and/or cores within the Center. Since individual projects, and preliminary data relevant to them, will be described in separate sections, only those collaborative activities/projects that bear directly on the proposed Center activities should be summarized here.
SECTION II. PROPOSALS FOR INDIVIDUAL PROJECTS AND CORES
A. PROJECTS: Identify each project by an Arabic numeral (1, 2, 3, etc.) and a title. For each component research project, a full description is to be provided following the format and page limits presented in Form PHS 398. Begin the presentation of each component research project on a separate cover page. The description of each project must be complete in itself, as different projects may be reviewed by different reviewers.
For each project, include the following information:
1. Face Page. Do not use the Form 398 face page; instead, use plain paper, and include the following information:
a. Project Title
b. Project Principal Investigator, degree, title, location
c. Other investigators, consultants, and collaborators, degrees, titles (Associate Professor, Postdoctoral Fellow, student).
2. Description, Performance Site(s) and Personnel (use Form Page 2 of PHS 398)
3. Budget (use the budget pages from Form PHS 398)
a. First year (use Form Page 4 of PHS 398 for each)
b. Total project period (use Form Page 5 of PHS 398 for each)
c. Budget Justifications: Describe the specific functions of key scientific and technical personnel, consultants, collaborators, and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For future years of support requested, justify any significant increases in any category over the first 12-month budget period. Identify such significant increases with asterisks against the appropriate amounts.
4. Resources and Environment (use the relevant pages from Form PHS 398)
5. Research Project Plan (Do not exceed 25 pages for Sections a-d)
In the Research Design and Methods section, in addition to the usual contents of this section, describe the research project's use of core unit services, including need for the services, and the advantages and cost effectiveness of core unit usage for the project.
B. CORES: Identify each proposed core unit by a letter (A, B, C..., core A being the Administrative Core) and a title (Administrative, Molecular/Cellular...). For each core, a full description is to be provided following the format and page limits presented in Form PHS 398. Begin the presentation of each core on a separate cover page. The description of each core must be complete in itself, as different cores may be reviewed by different reviewers.
For each core, include the following information:
1. Face Page. Do not use the Form 398 face page; instead, use plain paper, and include the following information:
a. Project Title
b. Project Principal Investigator, degree, title, location
c. Other investigators, consultants, and collaborators, degrees, titles (Associate Professor, Postdoctoral Fellow, student).
2. Description, Performance Site(s) and Personnel (use Form Page 2 of PHS 398)
3. Budget (use the budget pages from Form PHS 398)
a. First year (use Form Page 4 of PHS 398 for each)
b. Total project period (use Form Page 5 of PHS 398 for each)
c. Budget Justifications: Describe the specific functions of key scientific and technical personnel, consultants, collaborators, and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For future years of support requested, justify any significant increases in any category over the first 12-month budget period. Identify such significant increases with asterisks against the appropriate amounts.
For the Administrative core, the following additional points should be addressed in the "Research Plan" Section:
a. The authority of the Director
b. Advisory committees
c. An organizational framework and organizational chart
d. A contingency plan in case the Center director is unable to perform his/her responsibilities
e. Services that will be provided
For Research cores, be sure to address the following:
a. A decision making process for prioritizing use of the core unit
b. Plans for quality control
c. A summary table for the first year of the proposed grant showing the estimated use (percent) of the core unit by the component research projects
d. Cost effectiveness
e. Cost recovery, if any
C. PILOT AND FEASIBILITY PROGRAM
If a pilot and feasibility program is proposed, the following information should be provided.
Composite budget and justifications.
Introduction
Director and committees
Plans for the management of the pilot and feasibility program
Description of the pilot and feasibility program. This description should include justification of scientific proposals and a description of their core usage.
SECTION III - CHECKLIST - As required in Form PHS 398
3. Submission DatesApplications must be received on or before March 24, 2005 .
3.A. Receipt, Review and Anticipated Start DatesThe NIH intends to hold a pre-application meeting in Bethesda, MD at 9:00 AM on, December 10th, 2004 to which all prospective applicants are invited. NIH staff will make presentations that explain their goals and objectives for the Centers and answer questions from the attendees. FAQs and other information from this meeting will be available by contacting program staff at the addresses listed under Where to Send Inquiries .
Pre-Application Meeting Date: December 10, 2004
Letters Of Intent Receipt Date(s): February 24, 2005
Application Receipt Dates(s): March 24, 2005
Peer Review Date(s): June/July, 2005
Council Review Date(s): September, 2005
Earliest Anticipated Start Date: September, 2005
Expiration Date: March, 25, 2005
Prospective applicants are asked to submit a letter of intent that includes the following information:
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning of this document.
The letter of intent should be sent to:
Chief, Scientific Review Branch
N ational Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 3201
Bethesda, MD 20892
Telephone: (301) 496-9223
FAX: (301) 402-0182
Email: nindsreview.nih.gov@mail.nih.gov
Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. 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 or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:
Chief, Scientific Review Branch
N ational Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 3201
Bethesda, MD 20892
Telephone: (301) 496-9223
FAX: (301) 402-0182
Email: nindsreview.nih.gov@mail.nih.gov
Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf .
3.C. Application Processing
Applications must be received on or before the application receipt date listed in the heading of this funding opportunity. If an application is received after that date, it will be returned to the applicant without review. Upon receipt applications will be evaluated for completeness by CSR and responsiveness by the IC. Incomplete and non-responsive applications will not be reviewed.
The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application. These will be subject to the NIH policy requiring prior approval from the appropriate Institute or Center for applications requesting greater than $500,000 direct costs and applicants should use that opportunity to confirm that the application conforms to that Institute or Center's policies regarding unsolicited P50 grant applications.
Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.
Applicants requesting $500,000 or more in direct costs for any year must contact the IC program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study.
Plan for Sharing Research Data
The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.
Applicants requesting $500,000 or more in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing
The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.
Sharing Research Resources
NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication. NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131 . Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.
The adequacy of the data sharing plan and the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report. (PHS 2590). See Section VI.3. Award Criteria.
No additional criteria
2. Review and Selection ProcessApplications submitted in response to a funding opportunity will compete for available funds with all other recommended applications.
The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of these criteria in assigning the application's overall score, weighting them as appropriate for each application.
The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.
Significance : Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field?
Approach: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?
Innovation: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies?
Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)?
Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support?
3.A. Additional Review Criteria:Shared Resources (Cores)
1. Adequacy of the proposed plan to develop and maintain appropriate cores and potential for the distribution of reagents, cells, etc. within and outside the Center;
2. Degree to which plans indicate that shared resources effectively and efficiently support (or will support) the research of the Center in a manner that cannot be supported through available national resources;
3. Adequacy of the justification for each specialized resource relative to its essential need for the conduct of Centers subproject research or pilot projects and collaborative subprojects;
4. Adequacy of qualifications and performance (if applicable) of managers of resources;
5. Cost effectiveness of the requested budgets to conduct each resource operation.
Developmental Pilot & Feasibility Projects
1. Adequacy of the process for attracting new ideas for pilot studies within and outside of the Center institution(s). The process should include a mechanism within the institution(s) to solicit Pilot/Feasibility (P & F) applications and to oversee the use of funds for the proposed Pilot/Feasibility program. This process must also include plans to use the appropriate consultants from the scientific community external to the Center to review P & F applications.
2. Adequacy of the proposed process for continuously reviewing and funding a spectrum of pilot projects (e.g., research, technology development, resources) for their quality and importance to research that will have an impact on human disease.
3. Established mechanism within the institution(s) to solicit P & F applications and to oversee the use of funds for the proposed P & F program. This mechanism must include plans to include the use of appropriate consultants for review from the scientific community external to the center.
Overall Program Organization and Capability
1. Scientific qualifications and involvement of the Center's Principal Investigator, as well as his/her demonstrated scientific and administrative leadership capabilities; adequacy of the time commitment of the Principal Investigator;
2. Degree to which the organization and leadership of the Center promote and facilitate scientific interactions among subprojects, pilot projects, and Center infrastructure (e.g., shared resources) in the conduct of research;
3. Effectiveness of plans for promoting scientific interactions between basic and preclinical research at the Center;
4. Effectiveness of plans for integrating subproject research, cores and resources with Center programs;
5. Adequacy of tangible institutional commitments that will enable and facilitate the research objectives of the Center (e.g., special facilities, recruitments, discretionary resources such as dollars and space);
Interactions with Other Centers of Excellence in Translational Human Stem Cell Research
1. Adequacy of plans to promote and maintain communication between, and integration of scientific subprojects of mutual interest at other Centers of Excellence in Translational Human Stem Cell Research, and with the NIH in sharing information, in assessing scientific progress, in identifying new research opportunities and in establishing scientific priorities.
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section f of the PHS 398 research grant application instructions (rev. 5/2001) will be assessed.
3.B. Additional Review Considerations
After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm
A formal notification in the form of a Notice of award will be provided to the applicant organization. The notice of award signed by the grants management officer is the authorizing document.
Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA (Notice of Grant Award) are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
An award notice will be sent via e-mail to the Institution's business official.
Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually:
http://grants.nih.gov/grants/funding/2590/2590.htm and financial statements as required in the NIH Grants Policy Statement.
We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:
1. Scientific/Research Contacts:
NINDS
Paul A. Sheehy, Ph.D.
Program Director, Neurodegeneration Cluster
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Rm. 2214A
Bethesda, MD 20892-9529
(301) 496-5680 (v)
(301) 480-1080 (f)
sheehyp@ninds.nih.gov
NIDDK
Sheryl Sato, Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 6105
Bethesda, MD 20892-5460
Telephone: (301) 594-8811
FAX: (301) 480-3503
Email: ss68z@nih.gov
NHLBI
John W. Thomas, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10154
Bethesda, MD 20892-7950
Telephone: (301) 435-0065
FAX: (301) 451-5453
Email: thomasj@nhlbi.nih.gov
2. Peer Review Contacts:
Chief, Scientific Review Branch
N ational Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Room 3201
Bethesda, MD 20892
Telephone: (301) 496-9223
FAX: (301) 402-0182
Email: nindsreview.nih.gov@mail.nih.gov
3. Financial or Grants Management Contacts:
Michael J. Loewe
Chief, NINDS Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd., Suite 3290, MSC 9537
Bethesda, MD 20892-9537
Telephone: (301) 496-5707 FAX: (301) 402-0219
Email: loewem@ninds.nih.gov
Section VIII. Other Information
Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.
Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible. http://grants.nih.gov/grants/policy/data_sharing Investigators should seek guidance from their institutions, on issues related to institutional policies, local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.
Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html . Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov/ ) It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review.
Public 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 public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA 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.
URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.
Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople .
Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm .
The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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