and Human Services (HHS)
EXPIRED
Participating Organization(s) |
National Institutes of Health (NIH) |
National Institute on Aging (NIA) |
|
Funding Opportunity Title |
Interdisciplinary Approach to Identification and Validation of Novel Therapeutic Targets for Alzheimer's Disease (R01) |
Activity Code |
R01 Research Project Grant |
Announcement Type |
New |
Related Notices |
|
Funding Opportunity Announcement (FOA) Number |
RFA-AG-13-013 |
Companion Funding Opportunity |
None |
Catalog of Federal Domestic Assistance (CFDA) Number(s) |
93.866 |
Funding Opportunity Purpose |
This funding opportunity supports integrative, interdisciplinary research focused on the identification and preclinical validation of novel therapeutic targets within molecular networks involved in different stages of Alzheimer’s disease (AD) pathogenesis. The use of the multiple Program Director/Principal Investigator (PD/PI) option aims to maximize the potential of team science efforts necessary to achieve the programmatic goals of this funding opportunity. |
Posted Date |
October 15, 2012 |
Open Date (Earliest Submission Date) |
December 17, 2012 |
Letter of Intent Due Date |
December 17, 2012 |
Application Due Date(s) |
(New Date January 14, 2013 per NOT-AG-12-020), Originally January 13, 2013, by 5:00 PM local time of applicant organization. |
AIDS Application Due Date(s) |
Not Applicable |
Scientific Merit Review |
April/May 2013 |
Advisory Council Review |
August 2013 |
Earliest Start Date(s) |
September 2013 |
Expiration Date |
(New Date January 15, 2013 per NOT-AG-12-020), Originally January 14, 2013 |
Due Dates for E.O. 12372 |
Not Applicable |
Required Application Instructions
It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission
Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This funding opportunity supports integrative, interdisciplinary research focused on the identification and preclinical validation of novel therapeutic targets within molecular networks involved in different stages of Alzheimer's disease pathogenesis. The use of the multiple Program Director/Principal Investigator (multi-PD/PI) option aims to maximize the potential of team science efforts necessary to achieve the programmatic goals of this funding opportunity.
AD is the most common cause of dementia in those aged 65 and older. Because of the aging of populations worldwide, this disorder is reaching epidemic proportions, with an enormous human and economic burden. AD is one of the most persistent and devastating dementing disorders of old age, because it eventually leads to a complete loss of memory and of the ability to function independently. It is estimated that over five million people in the United States have AD in its various stages at an estimated cost to society of over $200 billion per year, and it is projected that 11 to 16 million people and their families could be affected by AD by the middle of this century if no effective therapies are developed to prevent, slow or stop the disease.
Currently there are only a few interventions that have been approved by the Food and Drug Administration to date for the treatment of AD and those approved have demonstrated only modest effects in modifying the clinical symptoms for relatively short periods, and none has shown a clear effect on disease progression.
In response to this looming public health crisis in the United States and worldwide, a growing number of countries are increasing their investment in all aspects of AD research. On January 4, 2011, President Obama signed into law the National Alzheimer’s Project Act (NAPA). As part of the Strategic Planning Process for the implementation of the National Alzheimer s Project Act (http://aspe.hhs.gov/daltcp/napa/) the National Institute on Aging at the NIH with support from the Foundation for the NIH (FNIH) organized and hosted an Alzheimer’s Disease Research Summit entitled: Path to Treatment and Prevention, held on NIH campus on May 14 and 15, 2012. The overarching goal of the Summit was to formulate a strategy for a new integrated, multidisciplinary research agenda that will enable the development of effective therapies (disease modifying and palliative) across the disease continuum for the cognitive as well as neuropsychiatric symptoms of Alzheimer’s disease and to identify the resources and infrastructure and public private partnerships necessary to successfully implement this translational agenda.
This funding opportunity announcement was developed in response to the recommendations of the AD Research Summit (http://www.nia.nih.gov/newsroom/alzheimers-disease-research-summit-2012-recommendations) related to the challenges in identification and selection of disease-relevant therapeutic targets.
Alzheimer’s disease (AD) is a highly heterogeneous, multifactorial disorder with a very long prodromal period. The complexities of the human brain and the disease process itself have been recognized as major impediments to the successful translation of basic discoveries to effective therapies for AD. One of the new concepts emerging in recent years is that AD is a network disorder affecting a large number of neuronal cell types, organized into functionally connected networks across many brain regions and not a disease of discrete lesions limited to specialized brain regions associated with cognition and learning. Within this network concept AD is viewed as a consequence of a shift from normal to pathological (perturbed) networks, and not just a response to a pathogenic change in a single molecular target. The lack of understanding of the molecular, cellular and physiological underpinnings of the normal to pathological shift in networks poses a special challenge in regards to the selection of truly disease-relevant therapeutic targets. Meeting this challenge requires new team science and a paradigm shift in basic and translational research towards integrative, network-based approaches.
This funding opportunity supports interdisciplinary and integrative research focused on identification and preclinical validation of novel targets for AD treatment and prevention. This initiative encourages the pursuit of paradigm-shifting biological and therapeutic hypotheses and promotes the creation of new translational teams consisting of epidemiologists, geneticists, basic research scientists, computational biologists, bioinformatics experts, medicinal chemists and pharmacologists within a research framework that will enable iterative cross-talk between basic and translational research.
The use of network-based approaches, such as systems biology and systems pharmacology to gain understanding of the molecular and physiological context within which potential therapeutic targets operate and in order to integrate target identification with early target validation is strongly encouraged.
In addition to demonstrating that a particular target is critically involved in a disease process, or in the development of a particular disease phenotype, applicants will be expected to demonstrate the potential druggability of the target (i.e. that modulation of the target with a small molecule/chemical probe or a biologic, produces a desirable, disease-relevant outcome).
Examples of tools and technologies to be used in the process of early validation are: conditional knock out/knock in transgenics (C. elegans, Drosophila, rodents), siRNA screens, chemical biology screens, and optogenetics among others. Applicants are expected to integrate the use of clinical samples and clinical data (genomic, epigenomic, imaging, histological, expression profiling, proteomic, metabolomic) with the use of animal or disease-related, cell-based models throughout the process of target identification and early validation.
Of particular interest are studies focused on the identification and preclinical validation of novel targets associated with i) molecular processes that lead to age-related decline in cognitive function, ii) mechanisms by which metabolic and vascular factors elevate AD risk, iii) mechanisms by which diet and exercise and other environmental factors modulate AD risk, and iv) mechanisms underlying the neuropsychiatric symptoms in AD.
Also of interest are studies focused on the identification and preclinical validation of novel targets associated with a variety of disease-relevant processes: mitochondrial bioenergetics, lipid dysregulation, neuroinflammation, proteostastis, neurogenesis, autophagy, endocytosis, the pathophysiology and trans-synaptic spread of tau, the risk-factor activity of ApoE e4 and the newly discovered AD genetic risk factors, amyloid beta clearance and others.
Emphasis should be placed on gaining a systems-level understanding of the gene, protein and metabolic networks within which these novel targets operate, and on quantifying the integrative response of a model organism to modulation of the target to gain early insight into potential adverse on-target and off-target effects. Identification of pharmacodynamic response biomarkers as part of the early validation process is strongly encouraged.
Funding Instrument |
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. |
Application Types Allowed |
New |
Funds Available and Anticipated Number of Awards |
NIH intends to fund an estimate of 3 - 5 awards, each with a duration of up to 5 years, corresponding to a total of $23 million in 2013. The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications. |
Award Budget |
For each application direct costs are limited to $1.0 million per year. Application budgets need to reflect actual needs of the proposed project. |
Award Project Period |
5 years |
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to
apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.
All Program Directors/Principal Investigators (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.
All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least 6 weeks prior to the application due date.
Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director/Principal
Investigator (PD/PI) is invited to work with his/her organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple
Program Director/Principal Investigator Policy and submission details in the Senior/Key
Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.
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.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Suzana Petanceska, PhD
Program Director
Division of Neuroscience
National Institute on Aging
Gateway Building, Suite 350
7201 Wisconsin Avenue
Bethesda, MD, 20892 (20814 for Express Mail)
Phone: 301-594-7754
Fax: 301-496-1494
Email: [email protected]
The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Resource Sharing Plan
Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:
Appendix
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.
Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.
Important
reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the
Credential field of the Senior/Key Person Profile Component of the SF
424(R&R) Application Package. Failure to register in the Commons and
to include a valid PD/PI Commons ID in the credential field will prevent the
successful submission of an electronic application to NIH.
The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application
Guide.
See more
tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Significance
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Innovation
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Approach
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?
Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Not Applicable
Renewals
Not Applicable
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIA, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH Grants
Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to the DUNS, SAM
Registration, and Transparency Act requirements as noted on the Award
Conditions and Information for NIH Grants website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
Not Applicable.
When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
Grants.gov
Customer Support (Questions regarding Grants.gov registration and
submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: [email protected]
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]
eRA Commons Help Desk (Questions regarding eRA Commons
registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]
Suzana Petanceska, Ph.D.
National Institute on Aging (NIA)
Phone: 301-594-7754
Email: [email protected]
Ramesh Vemuri, Ph.D.
National Institute on Aging (NIA)
7201 Wisconsin Avenue Suite 2C212
Bethesda, MD 20892-9205
Telephone: 301-496-9696
Email: [email protected]
Linda Whipp
Grants and Contracts Management Office
National Institute on Aging (NIA)
Telephone: 301-496-1472
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.
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NIH Funding Opportunities and Notices
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