Call for Stunning Microscopy Images—Deadline March 10

A collage of images showing taste buds on the tongue, nerve fibers, microtubules and actin filaments, small intestine, and plague bacteria.

In a few months, stunning microscopy images from NIH grantees will be featured in an exhibit called Life: Magnified.

The exhibit, a joint project of the American Society for Cell Biology (ASCB), NIGMS and the Metropolitan Washington Airports Authority, will run from June through November of this year at Dulles International Airport. This is an exciting opportunity to educate the public about cutting-edge biomedical research.

If you have images you’d like us to consider for display, please see the submission Web site Exit icon for image requirements and instructions. Submissions are due by March 10. You can contact NIGMS’ Alisa Machalek or ASCB’s Thea Clarke with any questions. You don’t have to be an ASCB member or an NIGMS grantee to contribute images.

If you find yourself near the C Concourse at Dulles later this year, I encourage you to stop by the Gateway Gallery to check it out.

International Year of Crystallography Is Under Way

A crystal of hen egg white lysozyme. Credit: Alex McPherson, University of California, Irvine.
A crystal of hen egg white lysozyme. Credit: Alex McPherson, University of California, Irvine.

As you may know from the coverage in various popular news outlets and science journals (see below for a list), the United Nations Educational, Scientific and Cultural Organization has declared 2014 to be the “International Year of Crystallography Exit icon.” This is in recognition of the 100th anniversary of the Nobel Prize in physics to Max von Laue for the discovery of diffraction of X-rays by crystals.

I first learned about crystallography in college, when I took a course in physical chemistry that included an introduction to chemical crystallography. Crystallography combines math, computer science, chemistry and biology—and that’s what convinced me to do graduate work in the field. When you determine structures, you’re often the first person to ever see that molecule, and that’s pretty exciting.

Since 1914, scientists have made many advances in the use of X-rays for the atomic-level determination of the 3-D structure of molecules. For instance, in the early years of the 20th century, William and Lawrence Bragg, father and son, learned that the newly discovered X-ray radiation could be used to locate the atoms in a crystal of matter. Their work ultimately led to Bragg’s Law for understanding X-ray diffraction and the structure determination of materials ranging from table salt to the ribosome. Breakthroughs made possible by crystallography (and diffraction) have led to 15 Nobel Prizes, including 7 with NIGMS support.

X-ray crystallography has impacted all areas of science, including biomedical research. The first biological finding was made by James Sumner, who discovered that enzymes could be crystallized (urease was the enzyme). In the years following, X-ray diffraction and crystallography have been used to reveal the structure of DNA and countless proteins and enabled structure-based drug design efforts. Crystallography has become an established tool of small molecule and protein studies.

Today, modern biological crystallography is practiced at synchrotron facilities, with access to 20 X-ray crystallography beamlines supported entirely or in part by NIGMS. Efforts are under way to make smaller, more intense beamlines that will allow the study of small crystals. Crystallography is also very much a part of the new X-ray laser facilities, where several NIGMS investigators are carrying out pioneering research on very small crystals of proteins, including membrane proteins, on X-ray scattering of proteins in solution and on protein dynamics.

Clearly, crystallography continues to be a cutting-edge field, and I’m excited to see what advances it brings during the coming years.

Articles about the International Year of Crystallography:

January 30 Special Issue of Nature Exit icon
UN to Raise Awareness of Little-Known Science Behind DNA, Computer Memory, New Drugs Exit icon
2014 Is the International Year of Crystallography (‘What’s Crystallography?’ You Ask) Exit icon

Funding Opportunities: Postbaccalaureate Research Education Program, Research on Issues Related to Central IRBs and Using Clinical Records and Data, Innovative Technologies and Assays in Support of HIV Research

You may be interested in these recent funding opportunity announcements:

Postbaccalaureate Research Education Program (PREP) (R25)
(PAR-14-076)

Purpose: PREP provides support for well-designed courses for skills development and extensive research experiences aimed at preparing individuals from diverse backgrounds to complete doctoral degrees.
Application receipt dates: March 31, 2014; January 25, 2015; and January 25, 2016.
NIGMS contact: Michael Bender, 301-594-0943.

Empirical Research on Ethical Issues Related to Central IRBs and Consent for Research Using Clinical Records and Data (R01)
(RFA-OD-14-002)

Purpose: This program furthers NIH’s commitment to enhanced protections for human subjects by encouraging research on the use of central Institutional Review Boards and on the use of clinical records and data.
Application due date: April 18, 2014.
NIGMS contact: Jeremy Brown, 301-594-2755.

Innovative Technologies and Assays in Support of HIV Cure Research (ITAS-Cure)
(PA-14-101) (R43/R44)
(PA-14-102) (R41/R42)

Purpose: ITAS-Cure encourages Small Business Innovation Research and Small Business Technology Transfer grant applications focusing on the development of sensitive and quantitative assays, methods or imaging techniques with commercial potential that can be applied to the measurement of residual HIV reservoirs in HIV-positive individuals on effective antiretroviral therapy.
Application due date: Standard AIDS application due dates apply
NIGMS contact: Mike Sakalian, 301-594-0829.

Wanted: Program Directors to Manage Grants in Developmental and Cellular Processes, Research/Student Research Development Programs

NIGMS is looking for two program directors (also known as “health scientist administrators/program officers”) to manage research grants and/or student research development program(s).

One position is in our Developmental and Cellular Processes Branch of the Division of Genetics and Developmental Biology. This branch supports research on the genetic and biochemical pathways that cells utilize in development and in normal physiological processes. Candidates should have expertise in the use of state-of-the-art molecular genetics and/or genomics-based approaches to address questions in these scientific areas.

The other position is in the Postdoctoral Training Branch of the Division of Training, Workforce Development, and Diversity. This branch supports research training, fellowship and career development programs for postdoctoral scientists. Candidates should have knowledge of and/or experience in understanding, planning and managing research/student research development program(s) at the postdoctoral or early stage investigator career level, including those targeted to groups that are underrepresented in biomedical and behavioral sciences. Candidates also should have expertise in innovations for teaching in STEM fields as well as research experience in other scientific areas within the NIGMS mission.

For both positions, candidates should have leadership, managerial, and strong oral and written communication skills. Familiarity with NIH extramural funding as a grant applicant, reviewer or NIH scientific administrator is a plus.

Vacancy announcements typically are open for only a very short time, and this one closes soon—Sunday, February 23. Please see the NIH HSA Web site for position requirements and application procedures. The Applying for Scientific Administration Jobs at NIGMS blog post offers additional background and tips.

Scientific Careers in the Federal Government

Broadening the definition of a “successful scientific career” is a key theme of the NIGMS training strategic plan as well as the NIH Biomedical Workforce Working Group Report.

To help graduate students, postdocs and even faculty become more familiar with the range of opportunities available to those trained for research, I participated in a 2013 ASCB meeting Exit icon  panel discussion with ASCB Executive Director Dr. Stefano Bertuzzi about science careers outside academia. We had a lively Q&A session about our reasons for leaving bench science, how our previous experiences have helped us in our current positions, and what one needs to do to prepare for careers in science policy and research administration.

Not too long ago, some might have considered me a science “dropout” because I left academia for federal work as a program director. I may no longer have my own lab, but I think about science every day and help researchers obtain funding for their work. I’m happy that I made the transition.

If you’re considering a science administration career in the federal government, here are a few tips to help you find available opportunities.

Job vacancies for individuals at all career stages are posted on USAJOBS.gov Exit icon. The Overview section of each announcement will tell you how many vacancies the job announcement intends to fill. Without going too far into the minutiae, the site has an advanced search Exit icon feature that lets you find open positions by salary, location, keyword and more. One search field is Occupational Series Exit icon. The series that may be of most interest to Feedback Loop readers are 0601 – General Health Science, which includes most scientific administration jobs at NIH, and 0401 – General Natural Resources Management and Biological Sciences, which includes science administration jobs at NSF. Both the 0601 and 0401 job “families” include bench science positions, as well.

As of today, the 0601 and 0401 series offered more than 80 open positions. While not all of the jobs may be relevant to you, this gives you an idea of the scope of the federal science and health mission.

Last year, Mitzi Kosciulek of NIH’s Office of Human Resources wrote about applying for scientific administration jobs at NIGMS. Some of the general principles she outlined are applicable to any federal job search. For example, as part of an effort to speed the hiring process, many USAJOBS postings are open for only 5 days. For that reason, consider creating a profile, building a resume in the system and uploading your academic transcripts so you’re ready to roll when the right job opportunity presents itself. Once you have a profile, you can save your most pertinent search specifications and then ask the system to send you new “hits” by e-mail.

Protein Structure Initiative Transition Planning Committees

Shortly after NIGMS Director Jon Lorsch announced plans to sunset the Protein Structure Initiative after the completion of the PSI:Biology phase in 2015, he commissioned two committees to determine what unique resources and capabilities developed during the PSI should be preserved and how that should be done. The committees, which are working together, held their first meetings in December and expect to present their recommendations within the year.

The external committee, which includes practitioners of structural biology and biomedical researchers who use structural biology data and resources in their work, will primarily focus on community needs. It also will suggest emerging challenges and opportunities in structural biology.

The internal committee, which is composed of NIH staff, will focus on how to implement the priorities identified by the external committee. The group includes a member from each NIGMS scientific division as well as several representatives from other NIH institutes who have experience managing structural biology and large, complex research programs.

The work of these committees will help define how we can provide continued access to important structural biology resources and identify new directions for technology development with potential for broad biomedical impact.

As Jon wrote in a Feedback Loop post about bolstering support for investigator-initiated research and as also reported in a Nature news article Exit icon, the decision to sunset a large set-aside program that has received substantial investments, such as the PSI, should not be interpreted as a lack of support for team science. Multidisciplinary collaborations are likely to become increasingly important as we delve deeper into complex biological problems, and we will continue to sponsor team approaches to biomedical research. We also remain committed to supporting structural biology research through investigator-initiated grant mechanisms, innovative technology development and access to critical resources.

Our Investigator-Initiated SBIR/STTR Program

In January, NIH and several other agencies issued new omnibus solicitations for the Small Business Innovation Research (PA-14-071) and Small Business Technology Transfer (PA-14-072) programs. A program descriptions and research topics document gives details about each funding component’s areas of interest. The NIGMS section begins on page 91.

Potential SBIR/STTR applicants often assume that, like some other federal agencies, NIGMS will be an end user of the tools, devices, products or services being created under the grant or will play an active role in their ongoing development toward eventual commercialization. As a result, we get questions like:

  • How can I ensure that my project offers what NIGMS needs?
  • Can NIGMS provide technical and/or regulatory assistance to help my project obtain FDA approval?
  • What clinical trial/technology development expertise does NIGMS have that I may access?

These assumptions are not correct. Like the vast majority of NIGMS-funded research, our SBIR/STTR program is investigator-initiated. Applicants propose what to do, how to do it and the best path toward commercialization. Although we may occasionally issue or participate in SBIR/STTR funding opportunity announcements targeted to stimulate activity in a specific area, these are still independent projects because we do not prescribe what the activity should be or how it should be pursued.

Our goal is to support innovative SBIR/STTR projects that could benefit the broader research and development communities and/or directly impact human health.

If you’re interested in applying for an SBIR/STTR grant in an NIGMS area of interest, you can get general advice and answers to many procedural and technical questions about the application and review process from NIGMS program and grants management staff. If you don’t know whom to contact, you can start by asking me your program questions or asking Patrice Molnar your grants management questions. If we don’t know the answers ourselves, we can refer you to others as appropriate.

You can also find useful information on the NIH SBIR/STTR Web site and in a recent blog post from NIH’s Sally Rockey titled What’s New with NIH’s Small Business Research Programs?

Funding Trends and Factors Affecting Success Rate

On January 17, the President signed into law the Consolidated Appropriations Act of 2014 Exit icon, funding the Federal Government for the remainder of the fiscal year and providing increased support for NIH relative to the post-sequester levels of 2013. The NIGMS Fiscal Year 2014 budget is $2.359 billion, which is about $66 million, or 2.9%, higher than it was in Fiscal Year 2013.

It’s too early to know what this will mean for the NIGMS grant application success rate—the number of competing R01 applications we fund divided by the total number of competing R01 applications we receive. A number of other, largely independent factors in addition to the budget can impact the success rate, as well. We hope that our latest analysis of NIGMS funding trends illuminates the interplay among some of these factors. Thanks to Tony Moore, Jim Deatherage and Ching-Yi Shieh for help with the data collection and analysis.

Figure 1 shows the percentage of R01 applications funded by NIGMS as a function of percentile scores for Fiscal Years 2009-2013. Fewer grants scoring above about the 12th percentile were funded last year than in the previous 4 years. In fact, the funding curves shifted more to the left each year in this period, except in 2012, which had a slightly better success rate than 2011. This was due in part to a dip in noncompeting R01 grants that had to be funded along with no increase in the number of competing applications relative to 2011. (For a 4-year R01, the second, third and fourth years are all noncompeting grants because they are funded without review by a study section. The funds required to pay the noncompeting awards are often referred to as “out-year commitments.”) Funding levels fell again in Fiscal Year 2013 due to the sequester cuts and increases in the numbers of competing applications and noncompeting grants (see below).

Figure 1. Percentage of competing R01 applications funded by NIGMS as a function of percentile scores for Fiscal Years 2009-2013. For Fiscal Year 2013, the success rate for R01 applications was 21%, and the midpoint of the funding curve was at approximately the 17th percentile. See more details about Figure 1 analysis.

Figure 2 presents a more granular view of the data for Fiscal Year 2013. The solid black bars correspond to the number of NIGMS competing R01 applications that scored at each percentile. The striped red bars show the number of these applications that we funded.

Figure 2. Number of competing R01 applications (solid black bars) assigned to NIGMS and number funded (striped red bars) in Fiscal Year 2013 as a function of percentile scores. See more details about Figure 2 analysis.

Figure 3 shows the success rate for Fiscal Years 2000-2013 (green line with triangles; right axis), the total number of NIGMS R01 applications each year (blue line with diamonds) and the number of funded competing R01 grants (red line with squares, left axis). Between Fiscal Years 2000 and 2003, the last year of the NIH budget doubling, the success rate was 37-38%. After the budget doubling ended, the success rate declined, falling to 26% in 2006. In 2007, the success rate jumped to 33%, largely due to a combination of a budget increase for NIH and a dip in the number of noncompeting grants NIGMS had to fund that year. (See below for more about changes in the number of noncompeting grants.) Over the next 6 years, the success rate for R01s dropped to 21%, the lowest level in two decades. Note that the Fiscal Year 2013 success rate for all research project grants (RPGs), which include R00s, R01s, R15s, R21s, R37s, P01s, DP1s, DP2s and U01s, was 19.9%. This is lower than the success rate for R01s alone, which was 21%.

Figure 3. Number of competing R01 applications assigned to NIGMS (blue line with diamonds, left axis) and number funded (red line with squares, left axis) for Fiscal Years 2000-2013. The success rate is shown in the green line with triangles (right axis).

One reason the success rate has fallen is that the number of applications increased between Fiscal Years 2002-2005 and then again between Fiscal Years 2010-2013. Similar trends are seen NIH-wide and are the result of a 50% increase in the number of investigators applying for grants along with a smaller increase in the average number of applications submitted per investigator.

Another factor that influences the success rate is the number of noncompeting awards. The more noncompeting awards we need to make in a given year, the fewer competing grants we can fund. The number of noncompeting RPGs cycles with a 4-year period, as shown in Figure 4.

Figure 4. Number of noncompeting (blue line with diamonds, left axis) and competing (red line with squares, right axis) RPGs funded by NIGMS for Fiscal Years 2000-2013. Note that the Y axes do not start at 0.

This cycle was apparently set in the early 1990s when the Institute shifted the duration of most competing RPGs from 5 to 4 years. The result was that the last group of 5-year awards and the first group of 4-year awards ended in the same year, creating a significant dip in noncompeting grants and a corresponding jump in competing grants that the Institute could fund. The bolus of grants awarded that year kept noncompeting commitments high for the next 3 years, until they all came up for renewal again. As you can see in Figure 4, the cycle has persisted to this day.

The cycle may lead you to wonder if you should try to time your application to correspond to a trough in noncompeting grants. You might get lucky and have all of the factors that drive success rate work in your favor. However, if other factors act to decrease the success rate, you might end up worse off. For example, even though 2011 was a trough year for noncompeting grants (Figure 4, blue line with diamonds), a jump in the number of applications (Figure 3, blue line with diamonds) worked in the opposite direction, and the success rate actually fell (Figure 3, green line with triangles).

Finally, the Institute’s budget is also a factor in determining the success rate. Figure 5 shows the NIGMS budget (red line with squares, left axis), the budget committed to competing and noncompeting RPGs (blue line with diamonds, left axis) and the ratio of the RPG budget to the total NIGMS budget (green line with triangles, right axis).

Figure 5. Total NIGMS budget (red line with squares, left axis) and budget committed to competing and noncompeting RPGs (blue line with diamonds, left axis) for Fiscal Years 2000-2013. The green line with triangles shows the ratio of the RPG budget to the total NIGMS budget (right axis). The jump in the NIGMS budget and corresponding drop in the RPG/NIGMS budget ratio occurred when large, primarily non-RPG programs were transferred to NIGMS along with their associated funds from the former National Center for Research Resources.

The Institute’s budget grew during the NIH budget doubling (1998-2003). It also jumped by nearly $400 million when the Institutional Development Award (IDeA) and Biotechnology Research Resources programs moved from the former National Center for Research Resources to NIGMS. A variety of pressures were responsible for the ~2% decline in the ratio of RPG funds to the NIGMS budget that occurred during Fiscal Years 2005-2011, including commitments to targeted initiatives and increased funding for training programs.

Because we don’t yet know the number of applications we will receive or the number of noncompeting grants that will end early due to retirements or other events, we can’t predict what our success rate will be in Fiscal Year 2014. We hope, however, that the steps we are taking to bolster our commitment to investigator-initiated RPGs will have a positive impact on the success rate.

Give Input on Training Activities Relevant to Data Reproducibility

Data reproducibility is getting a lot of attention in the scientific community, and NIH is among those seeking to address the issue Exit icon. At NIGMS, one area we’re focusing on is the needs and opportunities for training in areas relevant to improving data reproducibility in biomedical research. We just issued a request for information to gather input on activities that already exist or are planned as well as on crucial needs that an NIGMS program should address.

I strongly encourage you and your colleagues to submit comments by the February 28 deadline Exit icon. The information will assist us in shaping a program of small grants to support the design and development of exportable training modules tailored for graduate students, postdoctoral students and beginning investigators.

Biomedical Technology Research Resources: Funding and Access Opportunities

Our Biomedical Technology Research Resources (BTRRs)—until recently known as Biomedical Technology Research Centers—develop and disseminate cutting-edge technologies and methods that allow scientists nationwide to advance their projects beyond the levels that could be attained using commonly available laboratory resources.

If you’re a researcher who works collaboratively to create and integrate potentially transformative biomedical technologies and are interested in providing service and training to the scientific community, you may want to apply for a BTRR grant. The first step is to submit your concept in a pre-application. Feedback from its review can help you decide whether to submit a full application.

If you’re a biomedical researcher with a project in need of technology resources, you may be able to access them at an existing BTRR. The Biomedical Technology Resources Portal Exit icon includes descriptions of the available resources Exit icon, including those funded through NIH’s National Institute of Biomedical Imaging and Bioengineering, and instructions for accessing them Exit icon.

Before granting use of its technologies (whether remotely or in-person), the BTRR will evaluate your research project for demonstrated need as well as the level of engagement and assistance that would be required of resource staff. It’s also possible that, if your project has potential for advancing a newly emerging technology, you’ll be able to collaborate with BTRR investigators as they develop it. This close collaboration benefits your research and also furthers innovation at the BTRR.

For more details about the BTRR program, please contact me or Doug Sheeley.