New Program Announcements for Biomedical Technology Research Resources

I would like to call your attention to two program announcements recently published in the NIH Guide:

These announcements provide updated instructions for both pre-applications and full applications for Biomedical Technology Research Resource (BTRR) grants. The BTRR program supports development and dissemination of advanced technologies that enable biomedical research The BTRR centers create a wide range of technologies and work with thousands of NIH-supported investigators each year.

The X02 pre-application is strongly recommended. The pre-application provides an opportunity for prospective applicants to receive feedback from both peer reviewers and NIGMS program staff as they formulate their plans for a complex, lengthy proposal for a P41 grant.

Following an evaluation in 2016, we have revised the BTRR program, while preserving the fundamental mission of developing and providing access to advanced technologies. Susan Gregurick, director of our Biomedical Technology, Bioinformatics, and Computational Biology Division, presented on the evaluation and proposed program changes at the September 2016 NIGMS Advisory Council meeting.

Revisions to the program have changed the structure of a BTRR to give the investigators who run the centers more flexibility in how technologies are shared with the community. A new feature, “Technology Development Partnerships,” will enable centers to rapidly adopt and incorporate emerging technologies developed elsewhere that advance a BTRR’s overall mission, rather than focus entirely on technologies developed “in-house.”

The program also will provide investigators with greater flexibility to tailor a center’s approach to technology innovation, user access and training, and dissemination according to the specific technologies being developed and communities being served. At the same time, the program will place a greater emphasis on actively moving technologies out of the BTRR and into the wider community as quickly as possible. We anticipate that most BTRR centers will not be funded beyond three cycles (15 years), and we will require investigators involved with this program to formulate a sustainability plan for their research resources.

The submission date for the first round of X02 pre-applications is August 15, 2017. Future submission dates will follow a regular schedule, occurring twice per year in March and July. That timing allows nine months from submission of the X02 until the anticipated submission of a resulting full application in January or May, respectively.

The next submission date for full applications for a P41 BTRR is September 25, 2017. This is the only submission date for funding in Fiscal Year 2018. In future years, applications will be accepted twice per year, in January and May, with no September submission. To improve consistency in the review of competing applications, the NIH Center for Scientific Review will convene a special study section to review all NIGMS P41 BTRR applications together. There will be no site visits.

NIGMS also supports technology development through several other programs. To help investigators determine which technology development program is right for their project, we’ve posted a decision tree on the NIGMS website. It includes descriptions of the programs designed to support specific stages of technology development.

I welcome questions or comments about these FOAs or our technology development programs in general.

Funding Opportunity for National Cryo-EM Centers

NIGMS and the National Eye Institute (NEI) are leading a new NIH Common Fund program: Transformative High Resolution Cryo-Electron Microscopy. This initiative will establish national service centers to increase research capacity for molecular structure determination by high resolution cryo-electron microscopy (cryo-EM). The centers will provide access to state-of-the-art equipment, technical support and cross-training for the production and analysis of high resolution cryo-EM data. An open application process will offer equal-opportunity access to researchers nationwide.

The NIH Common Fund recently issued a funding opportunity announcement for these national centers. The application deadline is June 30, 2017, with optional letters of intent due by May 30. For more information about the cryo-EM centers announcement, please email me. Please also help us get the word out by letting your community know of this opportunity.

New NIGMS Technology Development Program Announcements

We would like to tell you about two new technology development funding opportunity announcements (FOAs) recently published in the NIH Guide. We previously wrote about the approval of these programs by our Advisory Council. They are part of an ongoing effort to facilitate early stage, investigator-initiated work to create or improve tools for biomedical research. We think the two FOAs briefly described below will stimulate early stage technology research and development by allowing scientists to focus on making the technology work before they begin to apply those tools to biomedical research questions.

Exploratory Research for Technology Development (PAR-17-046): This program will support modest 2-year R21 grants to develop a new technology or radically improve an existing one. Projects will be high-risk and have no preliminary data. The proposed technology should be justified by a significant biomedical research need, but the proposal should not include the application of the technology to a biomedical problem—it should focus on technology development.

Focused Technology Research and Development (PAR-17-045): This program will support R01 grants that are entirely focused on the development of an emerging technology with a strong potential to impact biomedical research. The program will not allow inclusion of a significant biomedical research problem because the technology will not be ready for that until the project is over. These grants will be renewable only once.

The deadline for the first round of applications is February 16, 2017.

To help investigators determine which technology development program is right for their project, we’ve posted a decision tree on the NIGMS website. It includes descriptions of the programs designed to support all stages of technology development.

We welcome questions or comments about these FOAs or our technology development programs in general.

Drug Design Data Resource: A Community Participation Project

If you develop or use software for structure-based drug design or generate data on drug target structures and ligand affinities, you may be interested in the Drug Design Data Resource (D3R) Exit icon. This is an NIGMS-funded project to collect and share high-quality protein-ligand data sets, develop computer-aided drug design workflows, and engage the community through blind prediction challenges.

The D3R, hosted by the University of California, San Diego, continues a program initiated by NIGMS under the Community Structure-Activity Resource (CSAR) Exit icon at the University of Michigan. A goal of this program has been to gather previously unpublished data from the pharmaceutical industry and other sources and to make it available for validating and improving software for predicting ligand poses and interaction energies. Several data sets have already been donated by companies, including Genentech, AbbVie, GlaxoSmithKline, and Vertex, as well as by academic groups. Both resources have also generated data sets internally or in collaboration with academia.

The data sets, which contain X-ray crystal structures of protein-ligand complexes and structure/activity data for multiple series of ligands, represent 13 different drug targets, including most recently for HSP90, MAP4K4, and designed steroid and vitamin D binding proteins. D3R has also collected data on host-guest systems and made this data available as part of the SAMPL Exit icon series of challenges for benchmarking software predictions of “simple” small-molecule chemical properties such as solvation free energy, partition coefficients, and binding to hydrophobic cavities.

Building on the success of its 1st Annual D3R Workshop Exit icon, in which the 2015 Grand Challenge Exit icon was discussed and summarized in a report, D3R just announced the 2016 Grand Challenge Exit icon. It is based on structures of the Farnesoid X receptor (FXR) and runs through February 2, 2017.

The resource also has developed a Continuous Evaluation of Ligand Pose Prediction Exit icon (CELPP) series of tests in collaboration with the World Wide Protein Databank Exit icon (wwPDB) and the Research Collaboratory for Structural Bioinformatics Exit icon (RCSB), another resource supported by NIGMS. The CELPP tests, which are distinct from the Grand Challenge, will provide chemical compound identifiers of bound small molecules in addition to the protein polymer sequence five days before release of 3D coordinates, giving developers an opportunity to predict docked poses each week.

D3R and its predecessor CSAR were developed to meet the needs of the drug design community identified during workshops several years ago. Continued community input and participation, including additional data donations, are important to help D3R fulfill its mission. Data releases can be coordinated with publication in other formats and venues. Contact D3R principal investigators Rommie Amaro and/or Michael Gilson or send email to drugdesigndata@gmail.com to see how you can be involved.

Early Notice: Revised Biomedical Technology Research Resources Program

BTRR September 2016 Advisory Council Presentation

My BTRR presentation at the September 2016 Advisory Council meeting begins at 2:23:15.

At its September 2016 meeting, our Advisory Council endorsed a concept for funding the Biomedical Technology Research Resources (BTRR) program. The concept includes a number of changes that reflect feedback from an expert panel of scientists convened by NIGMS to evaluate the program. In its report, the panel made important recommendations to:

  • Increase the flexibility and nimbleness of the program.
  • Incorporate a broader range of technologies into the program.
  • Increase new research directions and program turnover and implement a comparative review process.
  • Enable better integration of the program with the overall technology development plans at NIGMS.

The revised BTRR program will provide greater flexibility for the investigators to support a wider range of approaches for technology innovation and dissemination. The program will include collaborative subprojects to integrate emerging technologies in fast moving fields and to provide access and dissemination of these technologies. In addition, research resources funded through this program will have greater flexibility to tailor approaches for providing access, training users and disseminating the specific technologies to the communities being served.

These changes will better support the dual mission of the BTRR program: to develop high-impact technologies that enable biomedical research, and to move those technologies into wide use in the community.

We expect a funding opportunity announcement to be published in the NIH Guide later this year. In order to improve consistency in the review of competing applications, the NIH Center for Scientific Review will convene a special study section. We anticipate that most BTRR centers will not be renewed beyond three cycles (15 years) and we will require investigators involved with this program to formulate a sustainability plan for their research resources.

We welcome your input and feedback. You can email your comments to me or post them here.

NIH Request for Information: Metrics to Assess the Value of Biomedical Digital Repositories

NIH is requesting input from the community on existing and desired approaches for measuring and assessing the value of biomedical data repositories. The request for information (RFI) seeks input on a number of topics related to these repositories, including but not limited to:

  • Utilization metrics.
  • Quality and impact indicators.
  • Service indicators.
  • Governance and infrastructure metrics.
  • Use case studies.

RFI responses should be sent to NIH_Repository_Metrics_RFI@mail.nih.gov by September 30, 2016. Please see the RFI for additional information on submitting input.

If you have any questions about the RFI, please let me know.

Give Input on the Support of Biomedical Research Resources

NIGMS is considering how best to support two important activities: the development of biomedical technologies and access to those technologies as they become research resources. These topics are closely related, but there are aspects of each that should be explored independently.

Last summer, the Institute issued a request for information (RFI) on the support of biomedical technology development. The responses we received contributed significantly to initiatives for exploratory and focused technology development to be launched later this year. We now request your input in response to a new RFI on the need for and support of research resources (NOT-GM-16-103).

We’d like to know your thoughts on a number of topics, including:

  • The appropriateness and usefulness of existing research resources to the biomedical research community.
  • Examples of unmet needs for research resources.
  • The relative value of resources that serve many investigators versus specialized resources used by fewer investigators.
  • The value and manner of coupling technology development to research resources.
  • The review of research resource applications and the evaluation of funded projects.
  • The role of academia, other biomedical institutions and industry in developing and providing access to research resources.
  • The role of investigators and user fees in supporting institutional, regional and national resources.
  • The role of NIGMS in supporting research resources and technology development at various levels.

We also welcome any other comments that you feel are relevant to supporting research resources.

To respond to this RFI, send an email to nigmsresource@mail.nih.gov by June 3, 2016.

If you have any questions about the RFI, please let us know.

New NIGMS Initiatives for Supporting Technology Development

The January 2016 Advisory Council meeting presentation on the initiatives begins at 1:14:43

The January 2016 Advisory Council meeting presentation on the initiatives begins at 1:14:43.

We would like to tell you about two new technology development initiatives recently approved by our Advisory Council. These programs are part of an ongoing effort that we’ve previously described to facilitate early stage, investigator-initiated work to create or improve tools for biomedical research.

Developing and providing access to technologies that enable biomedical research is a high priority for NIGMS, as expressed in our 2015 strategic plan. Historically, support for technology development has generally been coupled to using the technology to answer a biomedical research question. Although in the later stages of technology development this coupling is often useful, in the early stages it can hinder exploration of innovative ideas that could ultimately have a big impact on research.

We think the two initiatives briefly described below will stimulate early stage technology research and development by allowing scientists to focus on making the technology work before they begin to apply those tools to biomedical research questions.

Continue reading

Support of Structural Biology and PSI Resources

The 15-year Protein Structure Initiative (PSI) ended on June 30, 2015. In preparation for the termination of the program, an external committee of structural biologists and biomedical researchers identified high-priority areas for NIGMS’ future support of structural biology and the preservation of certain PSI resources. Here are some of their key recommendations and what we’re planning to do in response.

Continue to support synchrotron beamlines for macromolecular crystallography.

Recognizing the importance of synchrotron beamlines in modern structural biology, we intend to continue to support these community resources. Part of this effort includes using a new funding approach to ensure that NIH-supported investigators have reliable access to mature synchrotron-based resources.

Maintain the technologies that make structural investigations possible at the most advanced level; meet the need for modern cryo-electron microscopy resources.

We’ll continue to use existing grant mechanisms to support structural biology research, including
X-ray crystallography, NMR, cryo-EM and integrative or hybrid methods. To facilitate the use of
cryo-EM for structure determination we have started a program to provide support for consortia of
cryo-EM labs to upgrade their facilities
. NIGMS is also developing plans for establishing regional
cryo-EM centers that could provide access to state-of-the-art cryo-EM resources for the broader structural biology community.

Continue reading

Early Notice: Mature Synchrotron-Based Resources Funding Opportunity Plan

At its September 2015 meeting, our Advisory Council endorsed a concept for funding existing NIGMS-supported synchrotron resources in which the technologies have become mature. This plan will align the funding mechanism used to support the beamlines with the goal of ensuring reliable access to these essential resources for structural biology.

In place of the variety of mechanisms we currently use, we intend to issue a funding opportunity announcement (FOA) called Mature Synchrotron Resources (P30) for 5-year, renewable grants in the range of $1-3 million per year in direct costs. The Institute intends to maintain overall support for mature beamline facilities at the same level it has in the past, but to replace the previous constellation of funding mechanisms with a single, more coherent one.

The focus of the FOA will be on user access, training and support in data collection, processing and analysis. Peer review will assess the resources primarily on their ability to meet the research needs of the user community and on the impact the resources have on their users’ scientific productivity. To ensure that the beamlines maintain their state-of-the-art operations, the FOA will also include support for a limited amount of technology development and implementation.

Since the goal of the effort is to improve the stability of current NIGMS-supported synchrotron structural biology resources for community use, the initial funding opportunity will be open only to synchrotron-based resources already supported by NIGMS.

We welcome your input and feedback on these plans. You can email your comments to me or post them here.

Charles Edmonds, Susan Gregurick, Ward Smith and Mary Ann Wu contributed to this blog post.