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.
I would like to draw your attention to proposed revisions to the federal policy for the protection of human subjects , often referred to as the Common Rule. Even if you’re not currently involved in human subjects research activities, your research might be affected by the proposed changes.
The modifications are intended to enhance the ability of individuals to make informed decisions about participating in clinical research and also to modernize and streamline the regulatory approval process. One of the major reforms would expand the definition of human subjects research to include the secondary use of human biospecimens, regardless of identifiability. Some of the other proposed changes would affect the processes for obtaining informed consent and for determining the exemption status of human subjects research activities.
I encourage you to review the notice of proposed rulemaking and submit comments by the December 7, 2015, deadline. Please note that each proposed change described in the document includes specific questions for public comment.
We congratulate our long-time grantee Steve Elledge of Brigham and Women’s Hospital on being recognized with the 2015 Albert Lasker Basic Medical Research Award for “discoveries concerning the DNA-damage response—a fundamental mechanism that protects the genomes of all living organisms.” He shares the honor with Evelyn M. Witkin of Rutgers University.
For a quarter century, we’ve funded Elledge’s investigations of the molecular underpinnings of this fundamental biological process. While working with the yeast model system in the 1990s, his group showed that the Rad53 kinase plays an important role in coordinating DNA repair with progression through the cell cycle.
More recently, Elledge and his team have identified over 1,000 candidate proteins that may participate in the mammalian DNA-damage response. They are now seeking to uncover the precise functions of these proteins.
The Lasker Award is a fitting occasion to reflect on how far we’ve come in this field and the exciting opportunities that lie ahead.
As I wrote in a previous post on the Pharmacogenomics Research Network (PGRN), we have been transitioning our support of pharmacogenomics research from set-aside funding to regular competition with other scientific areas. This is part of the Institute’s efforts to bolster support for investigator-initiated research. We’ll now fund pharmacogenomics research primarily through regular research grant mechanisms, such as R01s or well-justified P01s.
To learn more about how pharmacogenomics-related applications fare in review, our Office of Program Planning, Analysis, and Evaluation conducted an analysis of NIH-wide pharmacogenomics-related applications assigned to Center for Scientific Review study sections. The analysis showed that these applications have comparable success in the review and award processes as applications in other scientific fields. Even so, I still recommend that applicants include a cover letter describing the kinds of expertise they believe are needed for an appropriate review. This can be particularly beneficial for a multidisciplinary research area like pharmacogenomics.
Mike Rogers, who has directed the NIGMS Division of Pharmacology, Physiology, and Biological Chemistry for the past 22 years, retired today. Throughout his NIH career, Mike has been a champion for chemistry and its important role in biomedical research.
Before joining NIGMS 26 years ago, Mike worked for more than a decade in what is now the Center for Scientific Review, where he oversaw the Bioorganic and Natural Products study section.
Between these two positions, Mike completed a detail assignment on Capitol Hill working for Senator Ted Kennedy’s Health, Education, Labor and Pensions Committee, an experience that he says allowed him to see NIH from a different perspective.
Throughout his time at NIGMS, Mike has sought to build scientific bridges. He created the chemistry-biology interface predoctoral training program, which aims to cross-train students in both disciplines. He was instrumental in developing the large-scale collaborative project awards program that “glued” together scientists with diverse expertise to tackle big, unanswered questions in biology. More recently, he forged a link between two fields to help form the new field of quantitative and systems pharmacology. Along the way, he mentored and encouraged others to develop major NIGMS and trans-NIH initiatives, such as those in glycoscience, pharmacogenomics and synthetic organic chemistry.
I am pleased to announce the availability of the new NIGMS strategic plan. This document outlines many of the priorities and activities that the Institute will pursue over the next 5 years. It’s designed as a framework to both codify and focus our efforts, while still allowing us the flexibility to pursue untapped opportunities in areas relevant to our mission.
The plan, which incorporates valuable input from the scientific community, highlights the goals and objectives listed below. It also contains specific implementation strategies for each objective.
- Maximize investments in investigator-initiated biomedical research to drive fundamental scientific discoveries that advance understanding of human health and disease.
- Invest in and sustain a broad and diverse portfolio of highly meritorious research.
- Promote the ability of investigators to pursue new research directions, novel scientific insights and innovative ideas.
- Support the development of a highly skilled, creative and diverse biomedical research workforce.
- Assess Institute research training and education programs and policies to ensure that they achieve positive outcomes related to the NIGMS mission.
- Promote the identification of best practices to continually improve the quality of research training activities.
- Support the development of and access to essential research tools, resources and capabilities for biomedical research.
- Support access to essential research resources and the development of new technologies that enable novel scientific advances.
- Continue the development of institutional research capacities and communities.
- Advance understanding of fundamental biomedical research and the NIGMS role in supporting it.
- Use a broad range of approaches to inform the public about NIGMS goals, activities and results.
- Continue to engage in an open dialogue with the scientific community and other stakeholders about NIGMS programs, processes and policies.
In addition, the plan includes a goal related to the optimization of Institute operations.
Finally, the plan reiterates our commitment to the stewardship of taxpayer funds and an atmosphere of open dialogue, collaboration and shared responsibility with the scientific community. In that spirit, we welcome suggestions to help us become as efficient and effective as possible in the pursuit of our mission.
I recently had the opportunity to talk to Phil Bourne, NIH’s associate director for data science, about some of the current Big Data to Knowledge (BD2K) initiative activities. I asked him how they tie together his vision of a digital enterprise for biomedical research and how they might benefit NIGMS grantees.
Phil explained that the goal of his office, commonly referred to as ADDS, is to achieve efficiencies in biomedical research, such as by making it easier for researchers to locate and manipulate data and software. “If we could just achieve a 5 percent improvement in efficiency in research that would be, in NIH budget dollars, more than $150 million a year that could be spent on funding more people and doing more research,” he said.
An active area that we at NIGMS are engaged in with ADDS is sustaining biomedical data resources, of which we support a fair number. As someone who previously set up databases and who now oversees them, I’m very passionate about this topic. A key question is how to sustain support of data resources in the current research budget environment. Led by Phil’s team, NIH has issued a request for information on sustaining biomedical data repositories that seeks input on every aspect of maintaining these resources. I encourage you to share your ideas by the March 18 response date.
Training is important in Phil’s vision for a digital enterprise, too. He told me of a number of recent training activities at NIH, including a “software carpentry” workshop for experimental researchers to learn how to use a wide variety of analysis tools. In a blog post about this and another event, the ADDS office asks for suggestions on other types of data science courses to offer. They want to provide workshops that train more experimentally versed scientists to work with big data and take those skills back to their labs. In addition, the ADDS office is planning to stand up a workforce development center to catalog classroom and online courses in the data sciences.
Another effort that’s in the works is creating a virtual space called the Commons where researchers can share, locate, utilize and cite datasets, software, standards definitions and documentation. Phil anticipates that the first components of the Commons will be available in 2016.
I’m really excited about Phil’s efforts and believe that they will help drive the “data quantum leap” I described in my first Feedback Loop blog post.
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.