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.
Jon Lorsch recently posted a message about the responsibility that our grantee community shares with us to help the research enterprise thrive. One way that we have addressed this is by taking a hard look at the funding of investigators who are already well supported. As most of you know, in an effort to increase efficiency and to support as many outstanding scientists as possible, we have long required special advisory council approval for any grant that, in combination with the principal investigator’s (PI’s) other research support, would provide over $750,000 in direct costs.
We have now developed guidelines that we will use in awarding R01s and other research grants to investigators with substantial levels of long-term, unrestricted research funding from any source. Unrestricted funding means that it is not project-based and may be used to conduct research on a broad topic at the PI’s discretion. We consider such support substantial and long-term if it is over $400,000 in direct costs (excluding the PI’s salary and direct support of widely shared institutional resources) and extends for at least 2 years from the time the NIGMS grant would be funded.
Abiding by these new guidelines will enable us to fund additional labs, increasing the likelihood of making significant scientific advances. The guidelines will take effect for applications submitted on or after January 2, 2016. If you might be affected by the new guidelines, I encourage you to discuss your plans with your program director.
Using a technique made possible by super-resolved fluorescence microscopy, scientists captured this image of a cellular skeleton. More details
We were excited to learn this morning that our grantee William E. Moerner will share the 2014 Nobel Prize in chemistry with Eric Betzig and Stefan W. Hell "for the development of super-resolved fluorescence microscopy." We congratulate them on this well-deserved recognition of their pioneering work, which has provided an unprecedented window into the cell and paved the way for understanding a range of biological processes.
I’m particularly thrilled with today’s news because it highlights an NIGMS-supported field that I’ve been closely involved in for more than 15 years. I remember my first conversation with W.E. on moving single-cell spectroscopy into biology, which led to a 2000 workshop we held to explore the state of the art in—and potential for—research in single molecule detection and manipulation. The recommendations from that workshop informed the development of a number of initiatives to apply the tools and approaches of the physical sciences to biological problems. The initiatives include our single molecule detection and manipulation program announcement and an NIH Roadmap for Medical Research program on the development of high-resolution probes for cellular imaging.
Since then, we have witnessed an explosion in the use of optical methods to look at single molecules at the nanoscale level and are gaining a wealth of insights as a result.
A statement from NIGMS on the prize is at http://www.nigms.nih.gov/news/results/pages/20141008.aspx. More information about our support of Nobel Prize winners is at http://www.nigms.nih.gov/education/pages/factsheet_NIGMSNobelists.aspx and at http://www.nigms.nih.gov/pages/GMNobelists.aspx.
The National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory (BNL) closed earlier this week as a newer, more advanced facility, NSLS-II , began to come online.
Thousands of NIH researchers have used beamlines at NSLS over the last 30 years to collect data to characterize biological macromolecules including drug targets, ion pumps and enzymes. Because the beamlines for biological research at NSLS-II will not be available until 2016, other synchrotron facilities are temporarily expanding their capacity to address the beamline reduction.
Here are some sources that will help you identify and access beamlines at other U.S. synchrotrons:
If you have questions about NIH-funded synchrotron resources, please contact me or Ward Smith.
As part of the ongoing examination of our large-scale research initiatives and centers, we’re in the process of evaluating the NIGMS National Centers for Systems Biology program. This includes conducting quantitative analyses of the program’s contributions to systems biology research, training and outreach as well as gathering qualitative input from a panel of external scientific experts.
We expect the evaluation to be complete by early 2015. The results and recommendations will help us determine a future path for supporting this field in the most effective and efficient way and in the context of competing research funding priorities and opportunities. In the meantime, we’re only accepting renewal applications for projects seeking their second, and final, 5 years of funding.
Over the 10-year course of the program , we’ve funded 21 centers covering a broad range of areas, from structural and cell biology to physiology and pharmacology. To learn more about the current and past centers, visit the Centers Web site.
We congratulate long-time NIGMS grantee Peter Walter of the University of California, San Francisco, on being recognized with the 2014 Albert Lasker Basic Medical Research Award for his elegant and insightful work on the signal that activates the unfolded protein response (UPR). He shares the honor with Kazutoshi Mori of Kyoto University in Japan.
For more than 30 years, we have funded the Walter lab to investigate how yeast cells control the quality of their proteins and organelles to maintain homeostasis. In the 1990s, at the time Walter was conducting the research that led to this award, we supported his studies of protein translocation and the signal recognition particle, which links the nascent protein chain to the endoplasmic reticulum, where folding then occurs. This work led, in part, to his research on the downstream events associated with protein misfolding and his identification of the key signal that activates the UPR.
The UPR mechanism adjusts as needed to maintain normal cellular function and prevent disease. Sustained overactivation of the UPR has been implicated in cancer, diabetes, autoimmune conditions, liver disorders and neurodegenerative diseases. Additional studies have shown that the UPR is highly conserved and present in every cell.
The Lasker Award to Walter, who’s also an HHMI investigator, is a strong endorsement of question-driven basic research and its role in revealing unpredicted, medically important pathways.
The basic biomedical research NIGMS supports is essential for the groundbreaking advances that enhance human health, but drawing a connection between an NIGMS-funded research project and a specific medical advance can be difficult. First, it can be decades between the study of a scientific question and the application of the resulting knowledge to improving human health. Second, in most cases, it’s not a single project or experiment that leads to a “eureka moment” with tangible benefits, but rather the combination of many projects. Third, the projects may be supported by different funding sources (various NIH institutes, other federal agencies, private organizations and foundations), and these sources often change during the decades of development. What started as an NIGMS project may later get funded by an NIH institute whose mission is disease-specific, followed by private funding as the advance becomes commercialized.
We’re always looking for new ways to identify these connections, and we think you can help. We’re soliciting stories that make a clear association between NIGMS-funded research and improvements in health, well-being or other tangible benefits to the public and/or economy. We’re also interested in applications in medicine, industry, technology or elsewhere that have their roots in NIGMS-funded research projects. We especially encourage our long-time grantees to share their stories of discovery.
We’re not looking for “Nobel Prize”-type stories or scientific breakthroughs that might in the future lead to improvements in the human condition. Rather, we want complete stories that can trace current treatments, therapeutics or diagnostics back to knowledge or insights gained from one or more NIGMS-funded projects. These examples will augment our own staff’s efforts to identify such stories and help us further fill out the historical context of breakthroughs in basic research and their impacts.
We’re using the Challenge.gov mechanism for this purpose, which enables us to give monetary awards of $500 to winning entries. We’ll also post the winning stories on our Web site. Submissions are due by October 20, 2014, and we look forward to seeing what you send in!
The latest update brings the total number of PDB entries to 100,147.
The Protein Data Bank (PDB) just passed a major threshold—the release of its 100,000th entry. This free online repository of experimentally determined protein and nucleic acid structures, which NIGMS and other parts of NIH have helped fund since 1978, facilitates atomic-level insight into protein structure and function. PDB is widely used by the scientific community to study basic biological processes like transcription, translation, enzymology, bioenergetics and metabolism and also for more medically oriented investigations into disease mechanisms and drug design.
In addition to scientists, students and educators use the digital resource for their own explorations of protein structure, function and interactions as well as to gain greater knowledge about biology.
Approximately 260,000 visitors access PDB each month. Scientists around the world currently deposit about 200 structures per week, which PDB staff review, annotate and augment with links to other relevant biological data. To meet the challenges posed by large structures, complex chemistry and use of multiple experimental methods, the repository recently launched a software tool for structure deposition and annotation .
If you aren’t already a PDB user, I encourage you to check out its resources to see if they could help advance your research.