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New PSI:Biology Technology Development Opportunities

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psi_logoWe have just issued new program announcements to develop technologies for protein modeling (PAR-10-075, PAR-10-076) and high-throughput structural biology research (PAR-10-074, PAR-10-073). These announcements are part of the PSI:Biology initiative that will apply high-throughput structure determination to a broad range of biological problems. Advances in comparative molecular modeling and high-throughput approaches will play an important role in the success of this initiative.

Protein Modeling

The protein modeling announcements aim to increase the quality of protein structure models. Because they promote collaborative research and exploratory approaches in developing novel comparative modeling technology, we encourage applications from new and established investigators in mathematics, physics, computer science, statistics or other quantitative disciplines.

High-Throughput Structural Biology Research

These announcements solicit proposals for improved experimental methods and techniques for all aspects of structural biology investigations. We particularly welcome projects related to proteins that aren’t currently amenable to high-throughput structural determination by X-ray crystallography and/or NMR spectroscopy.

Successful applicants for all four announcements will become part of the PSI:Biology network.

I can answer specific questions about the modeling announcements, and Charles Edmonds can answer questions about the high-throughput ones.

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ASCB Meeting: It’s an Exciting Time for Cell Biology

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ASCB ProgramLast week, the American Society for Cell Biology held its 49th annual meeting Link to external website in San Diego. There were thousands of attendees, including many of our funded investigators as well as a few of us from NIGMS. As a new program director, I enjoyed meeting many of the grantees and applicants I’ve talked to on the phone or by e-mail. I met a few others, too, who stopped by the NIGMS booth to get information on funding opportunities.

I can’t even begin to come up with an exhaustive list of all highlights from the 5-day program, so I will share just a few.

I was most excited about how discoveries made using “simple” organisms, such as yeast and unicellular algae, are informing models of human disease in new ways. For example, studies of centriole biogenesis and cilia formation in invertebrates have provided a mechanistic understanding of human ciliopathic disorders such as Bardet-Biedl syndrome. Interestingly, the relationship between human disorders and basic research is a two-way street: By doing a genetic analysis of plant and invertebrate orthologs of genes mutated in people with Bardet-Biedl syndrome, researchers have identified an evolutionarily conserved ciliogenesis “toolkit.”

In his keynote symposium talk, Dr. Rudolf Jaenisch presented another way to think about model systems. He discussed the potential of deriving induced pluripotent stem (iPS) cells from patients, causing the cells to differentiate into a certain type or organ system, and then using the differentiated cells to test for patient-specific drug interventions or gene therapy treatments. There are still scientific and technical challenges, such as recreating the progression of disease development and pathology in a culture dish, but I think that using iPS cells to model human disease may revolutionize our understanding of the cellular basis of disease and, in turn, help us learn more about how normal cells work.

The meeting also stressed the importance of science outreach. During a plenary lecture about the role of NIH in supporting basic research, especially in cell biology, NIH Director Dr. Francis Collins also talked about the role of scientists in educating various groups on the intrinsic value and economic impact of scientific research. Dr. Lawrence S. B. Goldstein echoed this sentiment during his acceptance speech for the ASCB Public Service Award by describing how even small efforts, such as explaining the potential of stem cell research to your neighbor, can have a cumulative impact.

I left knowing that this is definitely an exciting time to be a cell biologist, and I’m already looking forward to the 2010 meeting in Philadelphia.

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Update on Funding Opportunities for Collaborations between Investigators with Animal Behavior and Molecular/Genomics Expertise

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The Collaborative Research for Molecular and Genomic Studies of Basic Behavior in Animal Models program announcement (PA-07-096) will expire on January 8, 2010. We will be reissuing this program announcement in 2010, but not in time for you to submit an application for the February or March R01 deadlines.

The purpose of PA-07-096 and its successor is to facilitate collaborative research between investigators with expertise in animal behavior and those with expertise in molecular biology and/or genomics that addresses questions about the mechanisms of behavior in animal models. The long-term goal is to develop new or enhanced animal models for studying aspects of behavior relevant to the NIH mission. We encourage applications from multiple PIs.

The first deadlines for applications submitted in response to the reissued program announcement will be June 7, 2010 (for new applications) and July 6, 2010 (for resubmissions). Beginning in June and July 2010, we’ll start accepting applications for the standard R01 deadlines: June/July, October/November and February/March.

Regardless of when you apply or resubmit an application for this reissued program announcement, you’ll need to use the new R01 application forms and instructions with shorter page limits.

Curious about what the reissued announcement will look like? Ask me!

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Fiscal Year 2009 R01 Funding Outcomes

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Fiscal Year 2009, which ended on September 30, was a time of unprecedented opportunities for NIH due to the American Recovery and Reinvestment Act. As I noted previously, NIGMS used Recovery Act resources to support a variety of funding mechanisms.We have now analyzed the overall results for R01 grants using both our regular appropriation and Recovery Act funds. These results are shown in Figures 1-3.

Figure 1. Competing R01 applications reviewed (open rectangles) and funded (solid bars) in Fiscal Year 2009. The thicker bars (blue) correspond to applications supported using regular appropriated funds, while the thinner bars (red) correspond to applications supported using Recovery Act funds (2-year awards).

Figure 1. Competing R01 applications reviewed (open rectangles) and funded (solid bars) in Fiscal Year 2009. The thicker bars (blue) correspond to applications supported using regular appropriated funds, while the thinner bars (red) correspond to applications supported using Recovery Act funds (2-year awards).
Figure 2. NIGMS competing R01 funding curves for Fiscal Years 2005-2009. For Fiscal Year 2009, two curves are shown. The thicker curve (black) corresponds to grants made with regular appropriated funds, while the thinner curve (red) includes grants made with both regular appropriated and Recovery Act (ARRA) funds.

Figure 2. NIGMS competing R01 funding curves for Fiscal Years 2005-2009. For Fiscal Year 2009, two curves are shown. The thicker curve (black) corresponds to grants made with regular appropriated funds, while the thinner curve (red) includes grants made with both regular appropriated and Recovery Act (ARRA) funds. The success rate for R01 applications paid with regular appropriated funds was 27%, and the midpoint of the funding curve was at approximately the 22nd percentile. This percentile is slightly lower than that for Fiscal Year 2008. The success rate for R01 applications paid with regular appropriated and Recovery Act funds in Fiscal Year 2009 was 32%, with a midpoint on the funding curve near the 30th percentile. The curve including Recovery Act-funded awards is fairly broad because NIGMS considered additional factors in making funding decisions for Recovery Act awards.

The total NIGMS expenditures (including both direct and indirect costs) for R01 grants are shown in Figure 3 for Fiscal Year 1995 through Fiscal Year 2009.

Figure 3. Overall NIGMS expenditures on R01 grants (competing and noncompeting, including supplements) in Fiscal Years 1995-2009. The dotted line shows the impact of awards (including supplements) made with Recovery Act funds. Results are in actual dollars with no correction for inflation.

Figure 3. Overall NIGMS expenditures on R01 grants (competing and noncompeting, including supplements) in Fiscal Years 1995-2009. The dotted line shows the impact of awards (including supplements) made with Recovery Act funds. Results are in actual dollars with no correction for inflation.

We are analyzing additional data on NIGMS funding trends and will be posting these results on the NIGMS Funding Trends Web site.

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Join a Discussion on the Impact of Modeling

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Using computers to model basic processes is becoming more prevalent across all areas of scientific research. Modeling can predict information about systems—weather forecasts have been based on computer models for decades—or simulate interactions that increase our understanding of fundamental processes like those within cells.

Give us your input on the impact of modeling in biomedical research during a meeting at NIH on December 15 and 16. You can join the discussion remotely through the NIH Videocast Web site. For videocast details, see the Day 1 and Day 2 videocast pages.

The meeting is hosted by the Interagency Modeling and Analysis Group (IMAG), which includes program directors from eight government agencies in the United States and Canada.

Participants in this year’s meeting, called “IMAG Futures,” will address modeling efforts at five biological scales: population, whole-body, cell-tissue-organ, pathways and networks, and atomic and molecular. For more information, see the meeting agenda.

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New Research Education Program to Enhance Diversity in the Neurosciences

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NIH Blueprint for Neuroscience Research

The NIH Blueprint for Neuroscience Research, which NIGMS actively participates in, recently announced the Blueprint Program for Enhancing Neuroscience Diversity through Undergraduate Research Education Experiences (BP-ENDURE).

The program will support the development of collaborative research education partnerships to increase the number of students from underrepresented groups who are well-prepared to enter and complete Ph.D. degree programs in the neurosciences. It will connect academic enhancement and research training activities at research-intensive institutions (such as those participating in the Jointly Sponsored Institutional Predoctoral Training Programs and the Initiative for Maximizing Student Development (IMSD) Program) and institutions that have substantial enrollments of undergraduate students from underrepresented groups majoring in areas relevant to the neurosciences. These activities must be designed to increase students’ interest in the neurosciences and better prepare them for graduate studies in the field.

The deadline to submit a letter of intent is February 24, 2010, and the application deadline is March 24, 2010. Please see the funding opportunity announcement or contact me if you need more information.

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Propose Research Using the World’s Most Powerful Supercomputer

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How to Get Involved

Watch Videocast on
Dec. 17, 2-4 p.m.

The Blue Waters petascale computing system, under construction by the National Center for Supercomputing Applications (NCSA) Link to external website at the University of Illinois, will be the most powerful computer in the world when it comes online in 2011. The National Science Foundation is currently soliciting proposals for computing time Link to external website to explore big questions that can’t be addressed with other existing computer systems.

We will be hosting a virtual workshop and applicant briefing on Blue Waters to encourage our grantees to develop high-impact community proposals for computing time on this very important new resource. Given the amount of NIGMS-supported biological and biomedical research that utilizes a variety of computing platforms, we think there are a lot of great research opportunities.

The videocast is scheduled for Thursday, Dec. 17, from 2-4 p.m. You will be able to access it at http://videocast.nih.gov/summary.asp?live=8324. During the discussion, we will tell you about the opportunity, identify areas of science within the NIGMS mission that may benefit from Blue Waters, and help interested scientists form collaborations to submit proposals.

Presenters include Jeremy Berg, Stephen Meacham from NSF, Eric Jakobsson and Thom Dunning from the University of Illinois, and John Moult from the University of Maryland. You may join the live discussion by e-mailing questions and comments via the NIH Videocast Web site or by sending them to me. You also can send me your ideas or questions ahead of time.

Because of the considerable NIGMS investment in protein folding and prediction of protein structure from sequence, we will explore this area during the videocast. We realize that many other areas within the NIGMS mission may also benefit from access to Blue Waters, and we welcome discussion about those as well.

We have also set up a Web site where you can post your ideas and interests in using Blue Waters and/or forming collaborations.

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First Human Embryonic Stem Cell Lines Approved Under New Guidelines Now Available

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NIH Director Francis Collins announced today that the first 13 human embryonic stem cell (hESC) lines to be approved under the new NIH Guidelines for Human Stem Cell Research have been placed on the NIH Human Embryonic Stem Cell Registry, and NIH grantees may now use them. These lines were not previously eligible for NIH funding under the 2001 guidelines.

Investigators whose grants were awarded with restrictions on using the funds for hESC research should check the registry to determine if any of the lines are suitable for their projects. Please see today’s NIH Guide notice for more details, including procedures on how to request that the award restrictions be lifted.

An additional 96 lines have been submitted for inclusion in the registry. We expect that more will become eligible for use in the coming months.

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NIH Public Access Policy

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What should I do?

I recently had several peer-reviewed scientific manuscripts accepted. As an NIH-funded investigator (with an intramural laboratory in the National Institute of Diabetes and Digestive and Kidney Diseases), I complied with the NIH Public Access Policy and deposited the articles in NIH PubMed Central. I also included the PubMed Central ID numbers (PMCIDs) in my CV list of scientific publications.

I wanted to take this opportunity to remind other NIH-funded investigators of the public access policy, which also requires the inclusion of PMCIDs in all applications and progress reports, including those for training grants and fellowships. If a PubMed Central submission by a journal is in process and you do not have a PMCID yet, you can indicate “PMC Journal – In Process” at the end of the citation. If you have submitted the manuscript and so far only received an NIH Manuscript Submission System reference number (NIHMSID), NIH will accept it as a placeholder for the PMCID.

One area of confusion is that PMCIDs are not the same as PMIDs assigned by PubMed.

NIH’s frequently asked questions helped guide me through the PubMed Central submission process, and you may find the information there useful, as well.

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New Resource to Address Glycoscience Bottlenecks

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There are over 750 human enzymes dedicated to glycan synthesis, catabolism and recognition. They include glycosyltrasferases (GTs) and glycoside hydrolases (GHs). While there is tremendous demand for these enzymes in the scientific community, few are available in sufficient quantities for synthetic purposes or for structural/functional studies. Not surprisingly, glyco-enzymes are exceptionally underrepresented in the Protein Data Bank.

To help overcome these bottlenecks, NIGMS is partnering with NIH’s National Center for Research Resources to provide a two-year Recovery Act supplement to the NCRR-sponsored Resource for Integrated Glycotechnology at the University of Georgia. The center will draw additional expertise from investigators at the University of Arizona and University of Wyoming to generate libraries of gateway and expression vectors for glyco-enzymes. The gateway and expression libraries for these enzymes will begin to be made available to the scientific community over the next few months.

The team also will work to express and distribute a subset of these enzymes. Your input for this expression effort is welcome. Please direct inquiries regarding these vectors/enzymes to Kelley Moremen.

This new repository for mammalian GT and GH libraries will speed expansion of the chemical space for carbohydrates as well as speed structural and biochemical studies of these enzymes. The resource should benefit multiple scientific communities and accelerate progress on both the basic biology of the enzymes and their use for development of screening tools (arrays), diagnostics and therapeutics.

The GT and GH expression vectors libraries also may be a useful resource for researchers planning to respond to the upcoming PSI:Biology program announcements mentioned in an earlier post.