and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
This Program Announcement (PAR) is developed as an NIH roadmap initiative (http://nihroadmap.nih.gov). All NIH Institutes and Centers participate in roadmap initiatives. The PAR will be administered by the National Institute of Mental Health (NIMH) on behalf of the NIH.
Title: Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (MLSCN)
Announcement Type
This is a reissue of PAR-05-060, which was previously released on March 1, 2005. This reissuance introduces a new funding mechanism, new application requirements as well as requires electronic submission through Grants.gov. Programmatic aspects of the original announcement remain the same.
Update: The following update relating to this announcement has been issued:
Notice: Applications in response to this Program Announcement must be prepared using the SF-424 Federal grant application instructions and forms included in the application package that are available at Grants.gov http://www.grants.gov. Applications must be submitted electronically through Grants.gov. Grants.gov provides a unified web site for interaction between grant applicants and the US Federal agencies that manage grant funds. It allows investigators and their organizations to electronically find and apply for grant opportunities from all Federal grant-making agencies. Grants.gov is the single access point for over 900 grant programs offered by the 26 Federal grant-making agencies and will have an unparalleled impact on the grant community.
Program Announcement (PA) Number: PAR-05-147
Catalog of Federal Domestic Assistance Number(s)
93.242
Key Dates
Release Date: July 29, 2005
Letters of Intent Receipt Date(s): August 16, 2005; December 21, 2005; April 20, 2006
Application Receipt Dates(s): September 14, 2005; January 18, 2006; May 18, 2006
Peer Review Date(s): December, 2005-January, 2006; April-May, 2006; August-September, 2006
Council Review Date(s): January 2006; May 2006; October 2006
Earliest Anticipated Start Date: February 2006
Expiration Date: March 24, 2006
Due Dates for E.O. 12372
Not Applicable
Additional Overview Content
Executive Summary
The Molecular Libraries Screening Centers Network (MLSCN), launched on June 15, 2005, is a new national high-throughput biological screening resource. The goal of the MLSCN is to empower the research community to use small molecule compounds in their research, whether as tools to modulate genes and pathways, as imaging probes in basic or clinical applications, or as starting points for the development of new therapeutics for human disease. The MLSCN will be the engine of discovery in the NIH Roadmap Molecular Libraries initiative. Using compounds from the MLSCN Small Molecule Repository and supported by the informatics capabilities of NIH's PubChem, the MLSCN will provide researchers with many new chemical tools to explore cellular functions at the molecular level. In order to achieve this goal, the ten network screening centers will screen a large collection of compounds in a variety of innovative assays to identify and subsequently optimize small molecules that selectively interact with specific biological targets or pathways. This large collaborative effort will accelerate the pace of the application of chemical biology to the understanding of biology and disease mechanisms. Through this Program Announcement with special review (PAR), the MLSCN is soliciting applications from investigators who have developed innovative assays and are interested in having them used in the MLSCN to screen a large number of compounds maintained in a central Small Molecule Repository, and furthermore, interested in expanding the utility of their assay(s) for producing useful in vitro and/or in vivo chemical probes.
Part II. Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates
Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
3. Reporting
Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)
Section VIII. Other Information - Required Federal Citations
Part II - Full Text of Announcement1. Research Objectives
The National Institutes of Health (NIH) is committed to a major effort to broaden access to high-throughput screening (HTS) technologies, and the information produced by these approaches, for researchers in academia, government, and non-profit institutions. The public sector has not yet taken advantage of the considerable potential of HTS to advance the understanding of biology and disease mechanisms because access by academic scientists to automated screening facilities and diverse compound libraries is very limited. The NIH Molecular Libraries and Imaging Roadmap initiative (http://nihroadmap.nih.gov/molecularlibraries/index.asp) has just launched the Molecular Libraries Screening Centers Network (MLSCN) on June 15, 2005, which aims to enable the rapid transformation of new scientific knowledge into tangible benefits for public health. This effort will empower multi-disciplinary academic teams to discover small molecule tools that can be used in basic biological and biomedical studies. Descriptions of the ten network screening centers are available at http://nihroadmap.nih.gov/molecularlibraries/fundedresearch.asp. For information on the network's first screening center, the NIH Chemical Genomics Center (NCGC), please go to http://www.ncgc.nih.gov.
The NIH wishes to enhance access to HTS capabilities for the academic community in order to speed the discovery of molecular research tools (e.g., ligands, imaging probes, and new activities of existing drugs) that will be available to the public sector. It is also anticipated that this MLSCN effort will catalyze scientific breakthroughs that will contribute to the identification of molecular entities or molecular classes that may accelerate the development of therapeutics by the private sector. Through this approach, NIH wishes to stimulate research in the following areas: 1) discovery of novel biological targets that can inform studies of cell function and disease mechanisms; 2) development, validation, and application of screening assays and disease models to evaluate the activity of novel small molecules; and 3) use of chemical genomic approaches to characterize the biology of genes of interest, cellular processes, and proteins associated with disease processes.
The MLSCN is a collaborative research network that comprises nine extramural centers and one NIH intramural screening center. The ten network screening centers are capable of screening 100-200 assays adaptable to HTS annually and a large number of HTS assays were submitted from the research community in response to the previous Program Announcement Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (MLSCN). Each screening center will implement innovative HTS approaches to identify compounds that are active in target-based and phenotypic assays using 96-well, 384-well or 1536-well plate formats, as appropriate to the specific assay and screening platform. A variety of biological assays to be used within the MLSCN will be solicited from the scientific community. The MLSCN, as a national research resource, will interface with other components of the Molecular Libraries Roadmap initiative, including the Small Molecule Repository, PubChem (http://pubchem.ncbi.nlm.nih.gov), and ongoing initiatives for cheminformatics and for technology development in the areas of assay development, chemical diversity, screening instrumentation, and algorithms for predicting biological activity of small molecules (see http://nihroadmap.nih.gov/molecularlibraries/grants.asp). The Small Molecule Repository will acquire and maintain a collection of up to 500,000 compounds, from both commercial and academic sources, with well-known or unknown biological activities and diverse chemical structures. The repository will distribute compounds to the screening centers for HTS. Within the MLSCN, HTS hits, the active compounds identified through initial screening, will be developed through optimization chemistry and further screening into useful bioactive probes that can be used by the scientific community to study molecular targets, cellular pathways, and potentially as starting points for drug development that will occur outside the MLSCN. The chemical structures of the compounds in the Small Molecule Repository, along with the related screening data, and assay protocols generated by the MLSCN will be deposited into a public database, PubChem. Information about the bioactive compounds will be made available to all researchers, who will be free to adopt them in biological and biomedical research studies. For funding opportunities supported by the Molecular Libraries Roadmap assay development initiatives, see website at http://nihroadmap.nih.gov/molecularlibraries/grants.asp.
Objectives of the Project
The objective of this Program Announcement (PAR) is to invite HTS assay applications to support the Molecular Libraries Screening Centers Network (MLSCN). The goal of the MLSCN is to optimize and implement a variety of innovative biological, biophysical and cell-based assays for biological targets or processes for which there are limited selective and potent small molecule modulators available to the public. Applications are invited from investigators who have developed innovative assays for use both in basic research and in therapeutics development programs, and who are interested in having them used within the MLSCN to screen the repository library. The MLSCN intends to select approximately 100-200 assays per year for implementation within the ten screening centers.
Services Provided by the MLSCN
The MLSCN will provide the following services for those assays accepted for this program.
1. Assay Implementation: The MLSCN will adapt, optimize and automate existing target-based and cell-based phenotypic assays obtained from the scientific community to 96-well, 384-well or 1536-well plate format as appropriate to the specific assay, screening approach, and level of throughput anticipated. The MLSCN will be capable of implementing assays using a variety of detection readouts such as absorbance, fluorescence, luminescence, scintillation proximity assay (SPA), fluorescence energy transfer (FRET), bioluminescence resonance energy transfer (BRET), biophysical readouts, and cell based imaging screens.
2. Compound Library: The Small Molecule Repository is in the process of expanding a compound collection of up to 500,000 compounds with known or unknown biological activities and diverse chemical structures, and it will maintain these compounds and distribute them to the MLSCN screening centers.
3. HTS Screening: The MLSCN will screen the repository compounds for biological activity in HTS assays to identify and confirm hits. Secondary assays, using a different readout, will be performed on initial hits in order to minimize false-positive results.
4. Optimization Chemistry: The MLSCN will provide a moderate level of optimization chemistry capabilities to provide analogues of initial hit compounds to improve properties such as potency and solubility. Chemistry efforts are expected to include designing initial structure-activity relationships (SAR) and generating analogues around a confirmed hit.
5. HTS Informatics: The MLSCN will provide informatics support to track compounds, assays, and screening data. PubChem will support investigators with information for obtaining active compounds for their use in further research by identifying a source for purchase or synthesis of particular compounds. Any users of the data deposited into PubChem will be required to acknowledge the source of the data.
Guidance for HTS Assay Application
HTS is rapid screening of large number of compounds in a biological assay. Since assays accepted by the MLSCN will be involved in high-throughput, robotic, testing of compounds from the repository, the assays submitted should be adaptable to HTS with reasonable effort. It is anticipated that many of these assays will need to undergo further development to be usable in HTS formats, and such development will be accomplished through joint efforts between the submitter and the MLSCN screening center that is selected to implement the assay. Assay applications will be evaluated in terms of the following characteristics:
1. Readiness for or adaptability to HTS: HTS assays are primarily characterized by miniaturization and automation, and are usually conducted in microtiter plates, such as 96-well, 384-well or 1536-well plates. Assays submitted for HTS should be well established and characterized. If achievable, assays should have simple procedures readily adaptable to automation. Steps such as centrifugation, filtration and extraction should be avoided. Homogeneous, i.e. mix and measure, assays are preferable.
2. Assay performance and robustness: Performance characteristics of an assay should be suitable and reliable for automated HTS. Assays should be robust, reproducible and meet minimum statistical thresholds for robotic screening. Robustness is a measure of the capacity of the assay to remain unaffected by small changes in method parameters and provides an indication of its reliability during normal run conditions. The Z'-factor, a calculated parameter, is commonly used to quantify assay performance, and it accounts for both the signal-to-background and the amount of variability in the assay. Assays with Z' parameters >0.5 are typically HTS compatible assays. The coefficient of variation (CV) determined from the entire sample and control wells of the microtiter plate should not exceed 10%. Reproducibility between plates and day-to-day experiments also provides useful information on how well the assay will perform.
3. Diversity of assay types: Assays developed for HTS can be roughly characterized as target-based or phenotypic assays. A biological target is a macromolecule or a set of macromolecules in a biochemical pathway. Phenotypic assays measure a signal which corresponds to a complex response such as cell survival, proliferation, localization of a protein, nuclear translocation etc. The molecular target is not assumed in a phenotypic assay.
The following are some examples of HTS assays: 1) target-based biochemical assays may include enzymatic assays (such as kinases, proteases and transferases), and receptor-ligand binding assays (such as those for G-protein coupled receptors (GPCRs), orphan GPCRs, ion channels, transporters, nuclear receptors, and new targets emerging from genetic and proteomic research in model systems and in human diseases; 2) cell-based assays could include functional assays, reporter gene assays and phenotypic assays for cellular processes and pathway analysis (e.g., viability assays for proliferation or apoptosis); 3) non-traditional targets of interest include transcription factors, nucleic acids, multimeric proteins, membrane proteins, and polymorphic gene products, and subcellular processes such as molecular trafficking and translocation, post-transcriptional editing or splicing of gene products, and protein or RNA stabilization; and 4) other assays of interest include those for metabolism, bioavailability, toxicity, and blood-brain barrier permeability.
To learn more about HTS assay development, please read the online comprehensive guidebook Guidance for Assay Development and HTS at http://www.ncgc.nih.gov/manual/toc.html and visit the ASSAY and Drug Development Technologies website at http://www.liebertpub.com/publication.aspx?pub_id=118. This is a peer-reviewed bimonthly journal that publishes articles, papers, and editorial commentary that emphasize early-stage screening techniques including assay design, target development, high throughput technologies and chemistry. Additionally, the Journal of Biomolecular Screening , the official Journal of the Society for Biomolecular Screening, is available online at http://jbx.sagepub.com.
Material and Data Sharing
Submitting investigators will be required to provide necessary reagents such as cells expressing recombinant enzymes/proteins, primary and secondary antibodies, tagged peptide substrates, and available positive controls (e.g., a known inhibitor of the target). Investigators are expected to adopt uniform policies, such as data sharing, and procedures recommended by the MLSCN committee. All screening data and descriptions/protocols for assays optimized for HTS by the MLSCN will be deposited in PubChem immediately after they have been verified for accuracy. All data generated by the MLSCN will be freely available to the research community in a form that will support redisplay and reanalysis, so that maximal utility of this research resource will be realized. See details of NIH data sharing guidance http://grants.nih.gov/grants/guide/notice-files/NOT-RM-04-014.html.
Project Oversight
As part of the larger Molecular Libraries Roadmap initiative, projects that are funded under this PAR are subject to oversight and evaluation by each of the following entities.
MLSCN ASSAY ACCESS COMMITTEE. This NIH committee will evaluate assay proposals for scientific merit and feasibility for HTS. The Scientific Review Administrator (SRA) for this panel will be an NIH review staff member, and the panel members will be primarily non-federal scientists. Recommendations of the MLSCN Assay Access Committee will be communicated to the NIH Project Team and to the MLSCN Steering Committee.
MLSCN STEERING COMMITTEE. The steering committee for the overall MLSCN consists of the Director (PI) of each of the screening centers and the Small Molecule Repository, as well as NIH Program Managers and Science Officers, and will be the primary operational governing board of the MLSCN. The functions of this group include: 1) recommending the assignment and scheduling of assays and tasks, 2) developing guidelines to standardize the validation of screening data in different types of assays across centers; and 3) developing uniform procedures and policies for assay validation, data quality measures, assessment procedures, and annotation conventions for data depositions in PubChem. NIH Resource Access X01 PIs should submit a letter with their application, agreeing to allow their application to be shared with the MLSCN Steering Committee members. The information in their applications will be kept confidential.
NIH PROJECT TEAM. The NIH Project Team will serve as the governing body that coordinates and oversees the interaction of NIH with the centers and the MLSCN Steering Committee.
Section II. Award Information1. Mechanism(s) of Support
This access process will use NIH Resource Access award mechanism X01, designated for applicants to obtain access to a NIH Resource via submission of applications and projects that can be carried out in a short period of time. This is a new mechanism of support developed by NIH. The Resource can be utilized by biomedical researchers as a service for HTS. Investigators do not need to provide funds or personnel to utilize the Resource.
2. Funds Available
Through its funding of the MLSCN, NIH will support the costs of assay automation, screening and optimization chemistry (http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-017.html). Applications received in response to this Program Announcement (PAR) will not receive any additional funds. Different funds are available to support early stage HTS assay development by the Molecular Libraries Roadmap assay development initiatives (see http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-05-011.html).
The total number selected will depend on the number of applications received, their relative scientific merit, and the general availability of funds for NIH Roadmap. The earliest possible selection date for applications submitted in response to this program announcement is December 2005.
Section III. Eligibility Information1. Eligible Applicants
1.A. Eligible Institutions
You may submit (an) application(s) if your organization has any of the following characteristics:
1.B. Eligible Individuals
Any 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. Investigators from Federal laboratories are invited to submit assay applications.
2. Cost Sharing or Matching
Cost sharing is not required.
3. Other-Special Eligibility Criteria
There is no limit to the number of applications an applicant may submit under this announcement.
1. Address to Request Application Information
The SF-424 application form and instruction are available at http://www.grants.gov. Applicants must use the version of SF-424 Form downloaded from the application package created for this Program Announcement (PAR) in order to submit via Grants.gov. For further assistance contact Dr. Ingrid Li (301) 443-5288 or [email protected]. Or seek help from Grants.gov customer support resources at http://www.grants.gov/CustomerSupport. Grants.gov Contact Center Phone Number: 1-800-518-4726.
Telecommunications for the hearing impaired: TTY 301-451-5936.
2. Content and Form of Application Submission
Applications must be prepared using the SF-424 Federal grant application instructions and forms included in the application package Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (MLSCN) that is posted at Grants.gov http://www.grants.gov. Applications must be submitted via Grants.gov.
Grants.gov, providing a simplified grant application process, is a centralized electronic online system to find and apply for over 900 grant programs from the 26 Federal grant-making agencies.
Foreign Organizations
Several special provisions apply to applications submitted by foreign organizations:
Proposed research should provide a unique research opportunity not available in the U.S.
The following instructions will apply for this PAR using SF-424:
An application should include Specific Aims, Background and Significance, Preliminary Studies, and Research Design and Methods:
Page limitation for Research Plan: 10 pages single-spaced (excluding appendices).
Appendix: up to two publications may be included in the appendix. The appendix may include original, glossy photographs or color images of data provided that a photocopy (may be reduced in size) is also included within the page limits of the research plan.
3. Submission Dates and Times
Applications must be submitted on or before the receipt date described below (Section IV.3.A). Submission times N/A.
3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date: August 16, 2005; December 21, 2005; April 20, 2006
Application Receipt Date(s): September 14, 2005; January 18, 2006; May 18, 2006
Peer Review Date: December 2005-January 2006; April-May, 2006; August-September, 2006
Council Review Date: January 2006; May 2006; October 2006
Earliest Anticipated Start Date: February 2006
3.A.1. Letter of Intent
Prospective applicants are asked to submit a letter of intent that includes the following information:
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning of this document.
The letter of intent should be sent to:
Ingrid Li, Ph.D.
Molecular Libraries Assay Access Project Team
NIH Molecular Libraries & Imaging Roadmap
National Institute of Mental Health/NIH/DHHS
6001 Executive Boulevard, Room 7185, MSC 9641
Bethesda, MD 20892-9641
Rockville, MD 20852-9641 (for express/courier service)
Telephone: (301) 443-5288
FAX: (301) 402-4740
Email: [email protected]
3.B. Sending an Application to the NIH
Applications must be submitted using the original SF-424 Forms downloaded from the application package Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (MLSCN) which is posted on Grants.gov.
3.C. Application Processing
Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.) Upon receipt, applications will be evaluated for completeness by CSR and responsiveness by the NIMH. Applications that are not responsive 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. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique.
Applicants will automatically receive acknowledgements once Grants.gov approves the submission, and are generally notified of the review and funding assignment within eight (8) weeks.
4. Intergovernmental Review
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. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).
6. Other Submission Requirements
PIs should submit a letter with their application, agreeing to allow their application to be shared with the MLSCN Steering Committee members. The information in their applications will be kept confidential.
Registration and Application Instruction for Submission of Applications via Grants.gov.
Three separate actions are required: (1) registration of the applicant's institution with the Central Contractor Registry, the Credential Provider, and Grants.gov; (2) registration of the applicant's institution and the principal investigator in the NIH eRA Commons; and (3) preparation of the application (SF 424) and additional documentation by the applicant and electronic submission by the Authorized Organizational Representative (AOR). Registration must be completed before the application can be submitted.
Applicants should immediately check with their sponsored research office to determine whether their institution is registered. Please note that the registration process could take up to two weeks. The institution's AOR is responsible for completing the registration process. Applicants should work with their AOR to provide instructions, detailed below.
What is an Authorized Organizational Representative (AOR)?
The AOR is the designated representative of the grantee organization in matters related to the award and administration of its NIH grants, including those that require NIH approval. In signing a grant application, this individual certifies that the applicant organization will comply with all applicable assurances and certifications referenced in the application. This individual's signature further certifies that the applicant organization will be accountable both for the appropriate use of funds awarded and for the performance of the grant-supported project or activities resulting from the application. This individual is also responsible to NIH for ensuring that the organization complies with applicable Federal laws and regulations, including required certifications and assurances, their application, and the terms and conditions of individual awards. Under NIH's eRA Commons, this individual is referred to as the Signing Official (SO). Although NIH requires that the grantee organization designate such an official, NIH does not specify the organizational location or full set of responsibilities for this official.
What does the AOR need to do as part of the application process?
The AOR must:
If the institution is not already registered in Grants.gov, how does an organization register to apply for the Resource Access Award?
For more information on the Grants.gov registration process, please see: http://www.grants.gov/GetStarted.
If the institution is not already registered in the NIH eRA Commons, how does an organization become registered?
Only an individual with signatory authority for the institution in grant-related matters can register an institution in the NIH eRA Commons. To register in the NIH eRA Commons,
Please ensure that the Principal Investigator (PI) who will be named on your application is also registered in the NIH eRA Commons. It is important to ensure that this individual has a Commons PI account, and that this account is affiliated with your institution. We recommend that this process be completed at least two weeks prior to the submittal date of the application through Grants.gov.
What must the applicant do to prepare an application?
The applicant must:
How does the applicant download and complete the application form?
How is the application submitted?
After t he applicant completes all sections of the application, he/she sends the entire application package as an e-mail attachment to the AOR. The AOR submits the application package. Details of this process are below.
The applicant
The AOR
What computer and software are required?
The AOR will need the following:
and
and
Note that regardless of which system is used to complete the application, it must be submitted by the AOR from a PC.
How will I know if the application was received?
An e-mail confirmation and a validation receipt will be sent to the AOR.
Whom do I contact if I need help?
For questions regarding the submission process, contact the Grants.gov customer support at [email protected], or call 1-800-518-4726 Monday-Friday, 7:00 a.m.-9:00 p.m. Eastern Daylight Time.
Plan for Sharing Research Data
Since the inception of the ML Roadmap, NIH has emphasized that in order to yield the maximum benefit, all physical and intellectual research resources should be publicly available. There are strong scientific arguments supporting this position. Small molecule probes that selectively interact with biological targets are key research tools for understanding the functions of proteins and for elucidating biological pathways. A collection of such probes that would allow the comprehensive study of all of the proteins and other gene products encoded by the human genome would be an invaluable contribution to biomedical research. It will take the combined efforts of researchers in the public and private sectors many years of using small molecule probes to completely characterize the biology of genes and proteins in health and disease, and then to use that information to develop approaches that will improve public health. Clearly, the open sharing of data, research tools, and resources will lead more rapidly to the identification and validation of novel targets for drug discovery, and will facilitate the rapid development of therapeutics by both the private and public sectors, with resulting benefits to public health, especially for rare or marginalized disorders.
All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.
The willingness to comply with the NIH data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.
Sharing Research Resources
Guidance for Community Resources The following data and materials generated or developed through the ML Roadmap initiative are expected to be community resources: (1) primary data from HTS and from secondary screens; (2) protocols for assays implemented in the MLSCN; (3) the chemical structures of compounds tested in the MLSCN; and (4) the optimization chemistry protocols for probe development conducted within the MLSCN centers. In keeping with this approach, NIH expects that (1) all assays and assay protocols submitted to the NIH under this PAR, and (2) biological screening data derived from implementing the assays in the MLSCN will be made readily available and accessible, consistent with other facets of the ML Roadmap http://grants.nih.gov/grants/guide/notice-files/NOT-RM-04-014.html.
It is NIH's understanding that the utility of the resources and data generated by the ML initiative will be maximized if they are treated as community resources and made broadly available, consistent with achieving the goals of the ML Roadmap. While NIH recognizes that under the Bayh-Dole Act, awardees have the right to elect title to subject inventions and seek appropriate IP protection, the data sharing and IP plans should take all of the above considerations into account. Applicants should provide clear explanations and rationales for their plans, especially for any proposed plan that involves principles differing from those described in this PAR.
A separate component of the IP plan should address any other data and resources that are expected to be generated by the grantees under this PAR. NIH encourages applicants to consider inclusion of "non-assert" language in IP plans for all potentially patentable inventions to ensure that, while an institution might apply for a patent on an invention, the institution would not attempt to enforce that patent against organizations utilizing the technology for research purposes.
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 resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization and by NIH Project Team staff when making recommendations about selecting assays for implementation within the MLSCN.
Submitting investigators will be required to provide necessary reagents such as cells expressing recombinant enzymes/proteins, primary and secondary antibodies, tagged peptide substrates, and available positive controls (e.g. a known inhibitor of the target).
Submitting investigators and MLSCN Centers will be expected to use Materials Transfer Agreement (MTA) approved by the MLSCN Steering Committee for transfer of assays and materials to the individual MLSCN Centers. The majority of transfers to not-for-profit entities should be implemented under terms no more restrictive than the Uniform Biological Materials Transfer Agreement (UBMTA). In particular, submitting investigators are expected to use the Simple Letter Agreement provided at http://www.nih.gov/od/ott/RTguide_final.htm or another document with no more restrictive terms, to readily transfer unpatented materials to MLSCN Centers.
Section V. Application Review Information1. Criteria
Only the review criteria described below will be considered in the review process.
2. Review and Selection Process
Applications that are complete and responsive to the PAR will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIMH in accordance with the review criteria stated below.
As part of the initial merit review, all applications will:
The following is the anticipated process for assay review and selection:
Assay Access Review Committee (SEP): Evaluate assay proposals for scientific merit and feasibility for HTS. The Scientific Review Administrator (SRA) for this panel will be a NIH review staff member, and the panel members will be primarily non-federal scientists. Recommendations of the Assay Access Committee will be communicated to the NIH MLSCN Project Team and to the MLSCN Steering Committee.
NIH MLSCN Project Team: Review summary statements and develop a balanced portfolio that is consistent with NIH-wide programmatic priorities. The list of assay proposals will be presented to the MLSCN Steering Committee for implementation within the screening centers network. Review the recommendations of the MLSCN Steering Committee regarding the choice and distribution of assays to specific centers and make final assignments of these assays to specific centers and give final approval for assay assignments to individual centers.
MLSCN Steering Committee: Review HTS assay proposals selected by NIH project team and develop a plan for distribution of assays to specific centers within the screening centers network based on the NIH Project Team's prioritization of assays acceptable for implementation, and information about existing capacity and expertise of each center such as assay target, cost, workload, detection system, etc.
The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed HTS assay will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.
1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or practice be advanced? Is this assay for a novel biological target or cellular process? Is there no known small molecule modulator for this biological target available? Is this class of target extensively investigated? Is there an adequate plan for evaluating the activities of the compounds identified in a high throughput screen, e.g., in secondary screens? Are there important and well-defined goals for the use of active compounds identified with the proposed assay, either as research tools or for therapeutics development?
2. Approach. Is the assay well established and ready for HTS? Is the assay pharmacologically validated? Is there sufficient preliminary data for assay validation? Is there an assay performance parameter calculated, such as Z-factor? Is the assay readily adaptable by screening centers to an HTS format that is primarily characterized by miniaturization and automation? Is the assay feasible and reproducible, and does it and meet minimum statistical thresholds for robotic screening? Is there an adequate plan for assay reagents? Is there an adequate plan for secondary assays to evaluate active compounds identified in primary assays?
3. Innovation. Is the assay development project original and innovative? For example: Does the assay challenge existing paradigms or practice; address an innovative hypothesis or barrier to progress in the field of HTS? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?
4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Are the investigators knowledgeable about assay development and screening compounds library? Is the proposed work appropriate to the experience level of the principal investigator and other researchers?
5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?
2.A. Additional Review Criteria:
In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:
Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed.
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 Form 398 research grant application instructions will be assessed.
Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.
2.B. Additional Review Considerations
Budget: Not applicable
2.C. Sharing Research Data
Data Sharing Plan: 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. The funding organization will be responsible for monitoring the data sharing policy. The presence of a data sharing plan will be part of the terms and conditions of the award. Program staff of the funding organization and NIH Project Team staff will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.
2.D. 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 (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.
The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant.
Submitting investigators will be required to indicate whether or not they have Material Transfer Agreements or Sponsored Research Agreements in place to use patented technology or assay reagents proposed in this application for non-commercial, research purposes. Investigators will be asked to provide documentation prior to assay being selected for implementation within the MLSCN.
3. Anticipated Announcement and Award Dates
Not applicable
1. Award Notices
After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.
The Principal Investigator who submitted the assay proposal will be notified by NIH staff if the assay has been selected for implementation in a specific MLSCN center. A Materials Transfer Agreement (MTA) signed by the assay provider and a screening center as recipient will be required.
2. Administrative and National Policy Requirements
Not applicable
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:
Ingrid Li, Ph.D.
Molecular Libraries Assay Access Team
National Institute of Mental Health/NIH/DHHS
6001 Executive Boulevard, Room 7185, MSC 9641
Bethesda, MD 20892-9641
Rockville, MD 20852-9641 (for express/courier service)
Telephone: (301) 443-5288
FAX: (301) 402-4740
Email: [email protected]
2. Peer Review Contacts:
Yong Yao, Ph.D.
NIH Molecular Libraries & Imaging Roadmap
Scientific Review Branch
National Institute of Mental Health/NIH/DHHS
6001 Executive Boulevard, Room 6149, MSC 9608
Bethesda, MD 20892-9608 (20852 for overnight couriers)
Telephone: (301) 496-9223
FAX: (301) 402-0182
Email: [email protected]
3. Financial or Grants Management Contacts:
Jane Lin
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6154M, MSC 9605
Bethesda, MD 20892-9604
Telephone: (301) 443-3858
FAX: (301) 443-2229
Email: [email protected]
Required Federal Citations
Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.
Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).
Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.
Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.
Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.
Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this 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.
Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).
Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. 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.
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.
Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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