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.
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.
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.
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.