Public Briefing for RFAs
Mouse Mutagenesis and Phenotyping: Developmental Defects (HD-99-007)
Mouse Mutagenesis and Phenotyping: Nervous System and Behavior (MH-99-007)
June 21, 1999

Two overheads were presented to illustrate some of the major goals and the coordination of the Mutagenesis and Phenotyping Facilities

• Slide 1 - Facility Goals
• Slide 2 - Mutagenesis & Phenotyping Facilities Coordination

Attendees were reminded of up-coming dates.

Attendees asked, and received, answers to questions.

Up-Coming Dates

Questions & Answers

1. Given that the facilities funded under MH-99-007 probably will find several mutants with developmental defects, and that the facility funded under HD-99-007 will probably find mutants with nervous system and behavioral phenotypes, how will the different facilities interact so that each can analyze mutants developed by the others?

We appreciate that a facility may produce phenotypes in which they are not interested, and that some of these phenotypes may be of interest to another facility. Sharing mutants between facilities is a major feature of these RFAs. This is an important reason why facilities will be funded under the cooperative agreement mechanism (U01), rather than the standard R01 mechanism. We hope that cooperation among the facilities and between the facilities and the NIH — through the oversight committees — will foster the exchange of mice among the facilities and distribution of mice to the scientific community.

2. By what mechanisms will the mice be shared, or distributed, between the facilities? Where will we get the funds to enable this sharing?

Each facility will meet regularly with its Oversight Committee, and describe the types of mutants being produced. The committee will recommend that particular mice be sent to another facility to be examined further. Additionally, each facility must be aware of the mutants that are produced by the other facilities, and they must make information about their own mutants available to the other facilities. A portion of the budget may be allotted to these activities.

3. How flexible is the number of Facilities to be established? Could there be more than 1 facility established under HD-99-007?

   A. There may be some flexibility. But, we won’t know whether we need to be flexible until we see the applications. The outcome of the peer review will help to determine what, if any, flexibility would be beneficial.

4. The RFA states that NIH will eliminate the potential for patenting mutant mice, sperm, and embryos. Likewise, will NIH prevent the patenting of genes?

   The Bayh-Dole Act stipulates that the U.S. Government will not interfere with a grantee’s right to derive economic benefit from their intellectual property, except under extenuating circumstances. NIH believes that the ready distribution of the mice developed by these facilities constitutes such an exceptional situation. This is because creation and distribution of new mouse models to the scientific community is one of the main purposes of these facilities, and because we are establishing these facilities in response to the community’s needs. NIH’s policy is that exceptions to the Bayh-Dole Act be defined in a fashion that is as least restrictive as possible. Thus, the decision was made to not extend the patent prohibition to also include genes and gene products.

5. Who will be the members of the steering committees for projects funded under the two RFAs?

The External Steering Committee (ESC) and the Neuroscience Steering Committee (NSC) will be composed of the PI(s) of the facility(ies), NIH program staff, and three other scientists with appropriate expertise who are not affiliated with any facility.

6. Who selects the steering committee members?

   NIH program staff.

7. Who is on the committee that provides oversight for the steering committees?

   A. The Mouse Genomics and Genetics Scientific Panel (MSP) will be made up of about 10 scientists who are not affiliated with any of the facilities. They will have broad expertise covering all aspects of the facilities, such as animal husbandry, databases, phenotyping, etc. The members will be selected by NIH program staff.

8. Are the PIs members of the steering committees for the facilities established under the two RFAs?

PIs will serve on the Neuroscience Steering Committee (which will oversee facilities funded under MH-99-007) or the External Steering Committee (which will oversee the facility funded under HD-99-007). Oversight of these two steering committees will be provided by the Mouse Genomics and Genetics Scientific Panel, which will not include any researchers affiliated with any of the facilities.

9. Do you see these RFAs as a way of establishing infrastructure? Do you consider this to be a pilot? Is there a static amount of money for these efforts, or do you plan to expand in the future?

These initiatives are building blocks for a broad and comprehensive course of NIH-funded research to enhance mouse genetics and genomics resources. Future initiatives to exploit these resources and encourage further research on mouse biology are important components of NIH’s long-term plans.

10. Establishing and maintaining a database can be very expensive. How do we apportion the funds between the database and the other components of the project?

The RFA states that one of the objectives of primary importance is to develop and maintain a database of all phenotypic data generated from mutants. This is not meant to be a comprehensive database from which generated data will be downloaded by scientists in the wider community. Such databases and repositories will be made available to accomplish these purposes. It is expected that databases developed by the facilities funded under the RFAs will minimally contain the data generated, and will be sufficiently flexible to permit downloading of data to common, public repositories currently established or to be established.

11. The Neuroscience RFA states that a website at each individual facility is not sufficient to disseminate data to the wider scientific community. Which databases will be used to accomplish this?

Several such databases are being developed, and further information will be available at the time of award. The important point for applicants to bear in mind is that it is preferable for applicants to propose a plan by which data, protocols, technologies, and biomaterials generated in grants funded under the RFA will be placed in common, public repositories that are widely accessible to the scientific community.

12. Will the NIH support the renovation of our facilities to enable them to be use by guest investigators? Can some of the funds from the RFAs be used for that purpose?

Technically, some of the funds can be budgeted for facilities renovations. However, we view the NIH funds as providing partial support for the project of guest investigators. We would like to see evidence of institutional commitment to provide additional support, for example, to do necessary facility renovation.

13. What is the proper balance of depth verses breadth?

An important goal of these RFAs is to establish facilities for generating mutants that ultimately will be studied by a wide range of scientists in the broader community. It is highly likely that more mutants may be generated that can be intensively studied by any one facility. One of the award criteria is that each facility will serve as a resource for the broader scientific community; consequently, breadth is of paramount importance.

14. Will all of the applications for the Neuroscience RFA be reviewed by the same review group?

Yes. In fact, all of the application for both of the RFAs will be reviewed by the same group of reviewers during the same review meeting.

15. So, is there going to be only one Study Section?

    Yes. There will be only one Review Group for all of the applications.

16. After awards are made, how long does NIH expect it to take for facilities to begin functioning?

We expect the facilities to be functioning within several months to a year of the award date.

17. How "large-scale" is large-scale mutagenesis?

Researchers should propose what they feel is both scientifically justified and feasible. Ultimately, this question is one to be addressed by the scientific review panel.

18. Given that NIH has issued these two RFAs, will similar investigator-initiated projects submitted in the future be considered for funding?

Yes. The NIH will continue to consider submission of investigator-initiated applications for mutagenesis and phenotyping. In fact, we expect the facilities that are being established through these RFAs to serve as focal points for other investigators. Thus, we hope that these facilities will enable many investigators to examine mutants for phenotypes in which they are interested. We expect applications from other investigators to take advantage of the mutants produced by these facilities.

19. Projects that are funded by these RFA will be subjected to restrictions for the good of the community (e.g., the prohibition against patenting mutant mice). This prohibition will only be beneficial if all similar projects — not only those funded with the RFAs — are subjected to the same restrictions. Are there plans to impose similar restrictions on other existing projects and on projects that may be funded in the future?

We would like to convert existing, and future, large-scale NIH-funded mutagenesis and phenotyping projects to cooperative agreements so that they can be monitored and coordinated along with the facilities funded by these RFAs. We think that this action may also enable us to prevent those projects from imposing proprietary restrictions on their mutant mice, hence limiting their wide availability to the scientific community.

20. Can we study mutants paid for by non-NIH sources (e.g., a biotechnology company)?

    Yes, but the expectation is that such animals will not be patented and will be made available to the wider scientific community. Contractual arrangements with third parties who provide funding for the creation of animals used by the facility will be expected to acknowledge this, and NIH will review such contracts prior to any award being made.

Additional Questions

1. Can one institution submit applications in response to both RFAs (i.e., the Developmental Defects RFA and the Nervous System and Behavior RFA)?

You may submit an application in response to each RFA. However, we believe that there is a low probability that a review group would give fundable scores to two applications from the same group. Generally, a successful application requires the undivided attention of a group of researchers. When a group prepares two applications, neither one is as good as it could be. Thus, one concern is that submitting two applications could prevent either one from being funded.

Of course, there might be benefits of having the Developmental Defects Facility and a Neuroscience and Behavior Facility at the same location. Accordingly, we do not wish to dissuade a group from submitting an application for each type of facility. If you choose to do so, be sure that each facility would stand on its own in the event that the other one is not awarded. Also, each application must clearly describe the advantages of having the other facility at the same location.

2. Can an applicant to one of these RFAs submit another application at the same time for an additional small project to do related work?

   No.