|
Frequently Asked Questions
On This Page:
General
- Can investigators apply for more than one RFA in this program?
Yes. For example, it is conceivable that an applicant may have the capacity to not only establish a mapping center but could also successfully compete for an award to be the Epigenomics Data Analysis and Coordinating Center (EDACC); and/or could successfully compete for the discovery of novel epigenomic marks, and/or the development of new technologies. Additionally, when disease-specific RFAs are announced by the Roadmap Epigenomics Program, the competition will be open to all investigators at eligible institutions.
- I am an NIH intramural investigator. Am I eligible to apply?
Yes. See special application instructions under Section IV.2. “Applications involving federal agencies” of each RFA.
- What if I still have questions after reading the FAQs?
You may call or email the Scientific/Research Contacts listed under Agency Contacts in Section VII in the specific RFA of interest.
- What should be included in the Letter of Intent (LOI)?
Your contact information, co-PI’s information (if applicable), your key personnel including institution affiliations for all of the above, what you are proposing, and what areas of expertise you think your application most covers. This last piece of information is valuable to the Review Administrators so that they can make sure the appropriate experts are represented on the study section.
Up to Top
All Center Applications
- How integrated will the Epigenomics Data Analysis and Coordinating Center (EDACC) and Reference Epigenome Mapping Centers (REMCs) be?
The EDACC and REMCs should be highly integrated. PIs from the EDACC and all REMCs will serve on the same steering committee, and data from all REMCs will be coordinated and analyzed in close collaboration with the EDACC to generate the finalized reference epigenome maps. Applicants should propose how this integration will work.
- How will the EDACC and REMCs be evaluated?
At minimum, the Notice of Grant Award (NGA) will establish specific metrics for the EDACC, REMCs, and other Roadmap Epigenomics Program funded projects. Concrete, quantitative milestones should be described in the center applications. Milestones for the funded centers will be negotiated with NIH program staff at the time of award and become a condition of the award. All Roadmap projects will be expected to report on the progress through their non-competing renewals.
An external scientific panel (with nominees provided by the Centers) will be assembled approximately twice a year to assess progress of the consortium and make recommendations for improvements.
- Are applications for foreign institutions allowed?
Applications from foreign institutions are not allowed. However, foreign components of applications are permitted provided they meet the criteria outlined in section IV.2 under “Foreign Organizations” of the RFAs.
- How many meetings will Center Directors be required to attend each year?
Center Directors should budget for two face-to-face meetings each year. One will be a Steering Committee meeting with the Center Director from EDACC, and any other RM epigenomics programs as deemed necessary by Steering Committee members and/or the Epigenomics Working Group. The other face-to-face meeting will be an all-hands meeting for the entire cadre of Roadmap Epigenomic Program investigators. It would be appropriate that the Center Director and one or two key personnel attend the all-hands meetings. Center Directors will also be required to participate in monthly teleconferences or videoconferences.
Up to Top
RFA-RM-07-013 – Reference Epigenome Mapping Centers (REMC) (U01)
- Why human embryonic stem cell (hESC) emphasis?
The scientific community has identified these cell lines as a critical source for reference epigenomes, at multiple meetings and workshops over the last 3 years, and as a necessary resource to gain better understanding of normal differentiation, development, and disease progression. For more information on the Epigenetics of Human Health and Disease workshop held March 19-20, 2007, see http://nihroadmap.nih.gov/epigenomics/brainstorming0307/.
- Are all REMCs required to have hESC capabilities and expertise?
Yes, each Center should have the capacity to grow and maintain the hESC cell lines that will be used for developing reference epigenome maps.
- Will the Steering Committee have the final say regarding which hESC cell lines and other cells/tissues will have the epigenomes mapped?
Yes. The Steering Committee should have the hESCs and other cell lines nominated by the Center Directors and justified as required in the FOA; but, collectively, the Steering Committee will determine which cell lines/tissues will have epigenomes mapped for the most comprehensive and global mapping efforts.
- Why are data released so rapidly?
The reference epigenome maps are considered a community resource. As such, the data generated by the centers must be made freely available as rapidly as possible, i.e. as soon as the data are verified. The specific data release policy for the consortium will be established with the NIH and the steering committee. Although mapping data are released, once verified, both individual centers and the centers as a consortium are encouraged to publish using data gathered as part of this effort.
- How would collaborations with disease RFA investigators work in terms of budget?
The funding under this RFA will be for the analysis of normal cells. Applications for the disease-specific RFA(s) should allocate budget to any REMC they interact with to provide specific epigenome mapping data that has not been previously submitted to the Epigenomics Data Analysis and Coordination Center (EDACC). Collaborative arrangements are likely to be subject to subcontract arrangements. Additional questions in this area should be directed to grants management staff listed in the RFAs.
- I plan to submit an application with a co-PI or with the multiple PI option. What percent effort do I need to commit to the Center?
If you submit with a co-PI, you must still commit the minimum 20% effort to scientific research and center administration. Although no minimum requirement is stated in the RFA for a co-PI, it is expected that a significant level of effort be committed to the program dependent on the specific roles that individual will have on the project.
If you use the multiple PI option, both PI’s must commit a minimum effort of 20%.
- How much technology development are the centers expected to conduct?
The primary objective of the REMCs is to generate mapping data. The centers are expected to keep up with the state-of-the-art in terms of technology, and by their very nature, are likely to contribute to incremental improvements in technology. However, technology development, per se, is not a focus of these centers. Please see RFA-RM-07-011 and RFA-RM-07-012 for support of technology development.
- Can I request a budget for equipment purchases?
The REMCs are expected to be fully operational upon funding and equipped to meet their milestones. A maximum of $300,000 may be requested in the first year only for the purchase of equipment.
- How much informatics and data analysis will be expected to occur in each REMC?
Each center must have personnel that will be able to communicate and work effectively with the EDACC. These individuals must be capable of providing data to the EDACC in the agreed upon format and will be expected to work very closely with EDACC personnel.
Centers are allowed and expected to publish on their own work, and the center should be staffed appropriately to conduct the relevant data analysis.
- Will all of the REMCs use homogenized technologies in developing maps that will be determined post award?
No. They will determine collectively through the REMC Steering Committee the selection of cells used for mapping. It is conceivable that some Centers may focus on specific types of marks, e.g., DNA methylation or histone modifications or non-coding RNAs, and some may include analysis of multiple marks. REMC applicants should propose analysis of marks that they possess expertise in and use whatever technology is available to them to do genome scale mapping of the epigenomic marks they propose.
- If an applicant proposes to map DNA methylation in the genome, should they propose to map all methylated CpGs in the genome?
No. Applicants should propose and justify when possible, functional marks, e.g., CpG methylation. There likely will not be an advantage to mapping all sites of DNA methylation unless there are scientifically justifiable reasons to map these sites. Applicants should make their best cases for what they propose mapping.
- If the REMCs succeed in reducing costs with technology advances over time as requested, what happens with the extra funding?
It is an ambitious goal that has been set for the REMCs to develop the comprehensive maps that are desired. If costs are reduced and goals are met ahead of schedule because of technological advances, there are some options that may be considered at the front end of this program, but flexibility will be important so that none of the following options are pursued. That said, additional cells may be mapped, animal models may be added, novel marks that have been discovered may be used to expand the maps. However, the NIH Epigenetics Working Group along with the REMC Steering Committee may solicit the scientific community to determine how best to use the developed infrastructure of the REMCs and utilize the Roadmap funds allocated to this effort.
- Is it required that we have extensive experience with 'in-house' hESC culture? Is any sub-contract acceptable for cell culture?
It is requisite that all REMCs have extensive experience with hESC culture, whether this is achieved by in-house capabilities or subcontracting, as long as it is a component of the REMC proposal.
- How many hESC lines, isolated primary stem cells and differentiated cell types should be included in our study?
As many cell types may be proposed that are commensurate with budget requests. Final determination of selected cell lines will be done by the REMC Steering Committee immediately post-award.
- How important, if at all, is it to exclude cancer cells? Can studies include HL-60?
It is not important to completely exclude cancer cells. It is conceivable that HL-60 may be included, but again the final determination of selected cells will be made post award by the REMC Steering Committee.
- Should we identify all non-coding (nc) RNAs or chromatin-associated ncRNAs?
Not necessarily. Only the nc RNAs that a best case can be made for as epigenomic marks.
- How much validation and follow-up is expected versus pure data gathering?
It is not critical to validate each mark mapped, but some level of validation is required prior to submission of data to EDACC. It is anticipated that some validation will occur via the activities of other Centers that may be mapping some identical marks by different methods, in perhaps different cell types.
- The new PHS 398 forms do not correlate well with the instructions in RFA RM-07-013 for preparing an REMC application. What are my options?
You may use either the older version of PHS 398 (4/2006) or the current version (11/2007). Both versions may be found at: http://grants1.nih.gov/grants/forms.htm. For additional information please visit: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-028.html.
Up to Top
RFA-RM-07-014 – Epigenomics Data Analysis and Coordination Center (EDACC) (U01)
- Will the EDACC be expected to create a publicly accessibly site for the Roadmap Epigenomics Program data?
No. The EDACC funds are not to be used for a publicly accessible site for data. The National Center for Biotechnology Information (NCBI) is creating a publicly accessible database for this purpose, and all data will ultimately be submitted to them. The applicant should explicitly propose how the data is envisioned to be sent from the Reference Epigenome Mapping Centers (REMCs) to the EDACC and then submitted to NCBI.
- I am a computational biologist and my expertise in epigenetics/epigenomics is weak. Will my EDACC U01 be considered responsive?
The EDACC RFA states that the applicant must have:
- demonstrated prior experience in successfully leading the coordination of intensive activities and high-throughput, large datasets such as those to be generated by the Roadmap Epigenomics Program;
- demonstrated prior experience in successfully leading the analysis of large and disparate datasets; and
- strong epigenomic scientific expertise that will be integral to the success of an EDACC.
Applicants not meeting these criteria risk a consideration of non-responsiveness. One suggestion would be to submit an application as co-PI with another person with the appropriate expertise to be sure that the criteria are met.
- Will REMCs be responsible for archiving?
No, archiving will be the responsibility of NCBI. The EDACC will submit clean, verified, and validated RAW and metadata to NCBI.
- REMCs will have some informatics capabilities – specifics? Data in relational database formats, can we assume the REMCs will have some capacities?
EDACC needs to be flexible to accept data from multiple formats. REMCs need enough informatics expertise and capacity to do some own data analysis. The EDACC essentially will serve as a collective analysis for the REMCs and should perform some validation cross centers.
- Will there be opportunities for the Steering Committee to register marks in a cell line that is available? In other words, is there a mechanism for EDACC to request data – for example, resequence or re-evaluate marks if using cell line with a rearranged genome?
EDACC will need to show how open communication with mapping centers will occur. The EDACC should be able to request a re-analysis of a particular mark if the data quality are questionable, or if the marks are found to be missing or needed in a particular cell line.
- Regarding the EDACC, it is stressed that 'common' and 'standard' data formats need to be developed. Is it expected that all standardized data formats be developed de novo, or will applicants be encouraged to apply existing data formats and information models, along the lines of what has been developed through initiatives like MGED or caBIG?
Existing data formats can be used in the application, provided that they are used as an example pending agreement by NCBI. EDACC (with help from NCBI) will insure that common data formats will be used for the program. It is important to provide an explicit proposed data format and how that format (existing or otherwise) will be useful for the mapping centers, the EDACC and NCBI. Flexibility to use other formats will be necessary. No one knows who the players will be; data formats, etc. Therefore, there is a need to demonstrate capabilities, but the EDACC should also demonstrate flexibility.
- Can you clarify the U01 mechanism?
The U01 is a cooperative agreement award mechanism in which the NIH and extramural scientists work in cooperation and partnership with each other. Under the cooperative agreement, the NIH role is to support and stimulate the recipients’ activities through the involvement in the research activities and by generally working jointly with the award recipients in a partnership. NIH staff does not assume direction, primary responsibility, or a dominant role in the activities. The major distinction between a U01 and R01 mechanism is that under the R01, all executive decisions are made by the PI without collaboration with NIH. Under the U01, the NIH has input on some decisions through input on the steering committee.
- Are there specific aspects of analysis that NCBI plans to manage?
NCBI will be responsible for analysis in the following ways:
- As it relates to developing the web interface – where the analysis of the interface will be informed largely by EDACC and community input
- As it relates to integrating the epigenomic data with other relevant NCBI-specific resources, such as dbGaP, dbSNP, etc.
These types of analysis that NCBI will be doing do not relate to generating the maps themselves. Analysis of the data from the REMCs, metadata, and other sources is the responsibility of the EDACC and the REMCs in collaboration.
Up to Top
RFA-RM-07-011 (R01) and RFA-RM-07-012 (R21) – Technology Development in Epigenetics
- What are the scientific goals of the RFA?
One scientific goal of these RFAs is to develop transforming technologies that would revolutionize epigenetic profiling or whole epigenome studies. A long term goal is to enable epigenetic profiling or whole epigenome studies of single cells. A second scientific goal of these RFAs is to develop revolutionary technologies that enable in vitro and in vivo imaging of epigenetic changes at the level of the cell or tissue, with the long term goal of imaging epigenetic changes in living organisms.
- Would a purely computational application be responsive to these RFAs?
Any purely computational application would not be responsive to these RFAs. However, if you submit an application with aims that address one of the “wet lab” objectives of the RFA, and there is a related computational component, this could be considered responsive.
- Is a letter of intent required?
The information provided in the letter of intent allows NIH staff to estimate the potential review workload and plan the review; however, a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application.
- Will these RFAs be reissued?
We hope to reissue this pair of RFAs for 2010 funding, contingent on both the success of the program and the availability of funds.
- Do I need preliminary data for the R21 RFA?
Preliminary data is not required for an R21 application; however, it is important to convey the rationale and feasibility of the proposed approach. This justification may include presentation of theoretical, computational or ‘wet’ preliminary work within the allotted space limitations. An R21 is an exploratory application; therefore, it is appropriate to undertake unproven technologies with sound scientific rationale.
- Do I need preliminary data for the R01 RFA?
It is expected that an R01 application would have sufficient preliminary data to demonstrate the feasibility of the proposed approach. A successful R01 applicant will have significant ‘proof-of-principle’ and propose in depth development and validation of the proposed technology.
- Are these RFAs restricted to mammalian cells or tissues?
No.
- Would the research I do be considered technology development in epigenetics?
Feel free to contact program staff (John Satterlee or David Balshaw) to solicit their opinion. They may be able to provide guidance to make your application more appropriate for these RFAs or suggest other funding opportunities. We are specifically interested in revolutionary technologies rather than evolutionary changes to currently existing technologies. These novel or transforming technologies or methodologies must have the potential to dramatically enhance the ability of researchers to generate and use epigenetic data and knowledge. Our highest priorities are in the development of technologies that enable epigeneticists to perform research that was previously not possible or that constitutes an order of magnitude or greater improvement on the current state of the art.
- I am not a US citizen. Am I eligible to apply?
Yes.
- My institution is not in the US. Am I eligible to apply?
Qualified investigators at non-US (foreign) institutions may apply.
- I am proposing to improve standard epigenetic technologies. Would this be responsive to the RFAs?
Only if you are proposing to improve these technologies an order of magnitude or more beyond the current state of the art in some quantitative measure such as sensitivity, cost, etc. If so, be sure to make this point in the required section on technological innovation. Applications proposing to make incremental improvements to standard technologies would not be responsive.
- The budget for my technology development application will be greater than $500,000 in direct costs. Do I require permission in advance?
No, however we strongly recommend that you contact program staff in advance to discuss your plans as well as the potential pitfalls of such a proposal. You should try to determine if the aims of your application are both fully responsive to the RFA and of significant programmatic interest. The budget should be commensurate with the research proposed.
Up to Top
RFA-RM-07-015 (R01) and RFA-RM-07-016 (R21) – Discovery of Novel Epigenetic Marks
- How are these two RFAs related to the overall Roadmap Epigenomics Program?
Through the Epigenomics Mapping Centers and Data Coordinating Center, the Epigenomics Roadmap Program will provide high resolution maps of epigenetic marks across the full human genome for a representative selection of cell and tissue types. The mapping centers will begin with established methodologies and the purpose of the Discovery RFAs is to develop and validate additional marks which would be incorporated into the comprehensive mapping strategies of the Centers.
- Is the study of the mechanisms by which putative marks are established responsive to these RFAs?
No. Investigators wishing to pursue such studies should consider submission to NIH through regular mechanisms and deadlines.
- Is the study of the role of epigenetic mechanisms in a particular biological process or disease responsive to these RFAs?
No. As part of the overall Roadmap Epigenomics Program, NIH anticipates that RFAs will be issued beginning in 2008 to fund applications supporting research on fundamental epigenomic changes or mechanisms underlying specific diseases; conditions of development or aging; or response to exposures (physical, chemical, behavioral, and social factors).
- Are these RFAs restricted to particular model systems or cell types?
RFA-RM-07-015 (R01) must include mammalian cells or tissues. RFA-RM-07-016 (R21) can explore novel epigenetic mechanisms in any model system including mammalian systems.
- I am not a US citizen. Am I eligible to apply?
Yes.
- My institution is not in the US. Am I eligible to apply?
Qualified investigators at non-US (foreign) institutions may apply for either RFA-RM-07-015 or RFA-RM-07-016.
- Do I need preliminary data for an R21 submission to RFA-RM-07-016?
Evidence of the ability to carry out the proposed studies, including facility with proposed methodologies, is required in all submissions. Preliminary data for the experiments proposed in the application are not required.
- Do I need preliminary data for an R01 submission to RFA-RM-07-015?
It is expected that an R01 application would have sufficient preliminary data to demonstrate the feasibility of the proposed approach.
- Will these RFAs be reissued?
We will consider a solicitation for R01 proposals in 2010, if funds are available, based on progress on R21s funded by RFA-RM-07-016, or developments in the field in general.
- Is the identification of known mechanisms (i.e., H3 K9 methylation) in an unstudied cell type considered discovery of a novel mark for the purposes of this RFA?
No. Discovery in the context of this RFA refers to a qualitatively distinct mechanism that result in a measurable non-genetic change (mark) at a particular locus of the genome. The absence or presence of this mark should reflect the functional state of this region of the genome.
Up to Top |
