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 “New NIGMS Initiatives for Supporting Technology Development”
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 “Support of Structural Biology and PSI Resources”
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.
Membrane proteins and large macromolecular assemblies are important targets for understanding cell function and for drug discovery, but their characterization presents unique technical challenges. We’re considering how best to help researchers meet these challenges.
To give the biomedical research community the opportunity to offer comments on this topic, we have just issued a request for information (RFI). We want your opinion on the most effective methods for the determination of membrane protein and large macromolecular assembly structures and/or the need for new tools to aid in structure determination of these proteins or protein complexes.
Continue reading “Comment on the Need for Support of Membrane Protein Structure Determination”
If you use genetically modified mice or work on a gene in another model organism for which a homolog exists in mice, the Knockout Mouse Phenotyping Program (KOMP2) may benefit your research. It’s a resource that generates mice carrying specific genetic mutations and systematically phenotypes them according to uniform, high quality-control standards.
KOMP2 targets a range of phenotypes in order to improve the chances of gaining preliminary insights into the function(s) of genes that influence multiple traits, including targeting genes for which no information is currently available. The resource also captures negative results and disseminates them broadly. It examines male and female mice and provides data down to the individual mouse level.
Continue reading “Resource Spotlight: Knockout Mouse Phenotyping Program”
We support a variety of resources for biomedical research, and we’re considering a new addition: one or more facilities for protein expression. These resources would offer protein expression expertise and high-throughput expression capability for the benefit of the entire research community.
We just issued a request for information (RFI) seeking input on the needs within the biomedical research community for such resources and the types of protein expression services that would be most beneficial. Examples might include the expression of proteins from a large number of sequences, orthologs and homologs; prokaryotic and eukaryotic protein expression; and expression for special needs, such as for large numbers of mutants, proteins requiring anaerobic expression, and the incorporation of nonproteogenic amino acids like seleno-methionine.
Continue reading “Comment on Potential New Resources for Protein Expression”
Cryogenic tanks filled with liquid nitrogen and millions of vials of frozen cells. Credit: Coriell Institute for Medical Research.
We have just funded a new, 5-year award to continue operation of the NIGMS Human Genetic Cell Repository, an important resource for the scientific community since 1972. The repository contains more than 11,300 human cell lines and 5,700 DNA samples derived from them. These high-quality, well-characterized and rigorously maintained resources, which you can order for a nominal fee, include:
- Specimens from individuals with inherited diseases, apparently healthy individuals and those of diverse geographic origins that are divided equally between those from males and those from females.
- A group of 39 induced pluripotent stem (iPS) cell lines that carry disease gene mutations or that are normal control iPS cell lines.
- An inherited disease collection that represents almost 900 disorders.
Last year, 1,500 scientists received more than 5,000 cell lines and 40,000 DNA samples. I encourage you to peruse the catalog and consider whether these specimens may be useful in your research program.
I previously told you about the formation of two committees focused on Protein Structure Initiative (PSI) transition planning. These committees were charged with identifying high priorities for future NIGMS investments in structural biology and determining what unique resources and capabilities developed during the PSI should be preserved to address the needs of the scientific community. Dr. Leemor Joshua-Tor, one of the committee co-chairs, presented the groups’ report at the National Advisory General Medical Sciences Council meeting on January 23.
The committees’ recommendations for preserving PSI resources that the committees felt will be important for the community in the future include:
- Support for a modest number of protein expression resources to serve the needs of the community.
- Continued support for a materials repository similar to the one that has been supported through PSI.
- Possible continued support for a structural biology knowledgebase .
The committees identified these areas as high priorities for the future of structural biology:
- Continued support for synchrotron beamlines for crystallography.
- Support for modern cryo-EM resource centers.
- Continued support for NMR resources for structural biology.
- Support for the integration of structural biology methods.
- Support for collaborative, multi-investigator efforts in membrane protein and large macromolecular assembly structure determination.
We’re now developing plans for implementing the report’s recommendations.