Year: 2016

Notes from the Diversity Program Consortium Annual Meeting

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DPC Annual Meeting Program CoverAfter attending the Diversity Program Consortium (DPC) Link to external website annual meeting in mid-October and learning about the progress the consortium has made and its future plans, we’re feeling energized as we begin the third year of this grant. The DPC, supported by the NIH Common Fund and managed by NIGMS, is a cooperative agreement focused on finding the best ways to improve research training and mentoring in the biomedical sciences and on engaging a more diverse field of individuals in biomedical research careers. The consortium includes three interconnected programs: Building Infrastructure Leading to Diversity (BUILD), the National Research Mentoring Network (NRMN) and the Coordination and Evaluation Center (CEC).

The annual meeting brought together over 100 representatives from NIH and each grantee site to discuss DPC achievements, challenges and opportunities. The agenda, organized by the CEC, included two full days of presentations and breakout sessions.

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New NIGMS Technology Development Program Announcements

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We would like to tell you about two new technology development funding opportunity announcements (FOAs) recently published in the NIH Guide. We previously wrote about the approval of these programs by our Advisory Council. They are part of an ongoing effort to facilitate early stage, investigator-initiated work to create or improve tools for biomedical research. We think the two FOAs briefly described below will stimulate early stage technology research and development by allowing scientists to focus on making the technology work before they begin to apply those tools to biomedical research questions.

Exploratory Research for Technology Development (PAR-17-046): This program will support modest 2-year R21 grants to develop a new technology or radically improve an existing one. Projects will be high-risk and have no preliminary data. The proposed technology should be justified by a significant biomedical research need, but the proposal should not include the application of the technology to a biomedical problem—it should focus on technology development.

Focused Technology Research and Development (PAR-17-045): This program will support R01 grants that are entirely focused on the development of an emerging technology with a strong potential to impact biomedical research. The program will not allow inclusion of a significant biomedical research problem because the technology will not be ready for that until the project is over. These grants will be renewable only once.

The deadline for the first round of applications is February 16, 2017.

To help investigators determine which technology development program is right for their project, we’ve posted a decision tree on the NIGMS website. It includes descriptions of the programs designed to support all stages of technology development.

We welcome questions or comments about these FOAs or our technology development programs in general.

Stephanie Constant to Direct NIGMS Office of Scientific Review

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Photo of Dr. Stephanie L. ConstantI’m pleased to announce that Stephanie Constant will be joining us in early 2017 as the new chief of our Office of Scientific Review.

Stephanie is currently a scientific review officer at NIH’s National Heart, Lung, and Blood Institute, where her review portfolio is primarily focused on training and career development programs to promote diversity in the biomedical workforce. She also worked on detail in NIH’s Office of Extramural Research, where she contributed to developing and updating policy guidelines to enhance the NIH peer review process. Prior to joining NIH, she was a tenured associate professor in the Department of Microbiology, Immunology and Tropical Medicine at George Washington University. Her research included studies on the regulation of leukocyte migration in acute and chronic inflammation and on the mechanisms of immunomodulation by parasite products.

Stephanie’s deep knowledge of NIH review policies and practices and expertise in the review of training and diversity grant applications make her an ideal fit for this key position in our Institute. Please join me in welcoming her to NIGMS.

For more about Stephanie, see our news announcement.

Your Perspectives: Catalyzing the Modernization of Biomedical Graduate Education

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NIGMS actively supports efforts to catalyze the modernization of biomedical graduate education. We have undertaken a number of initiatives to stimulate this process, including hosting a symposium to showcase innovations in biomedical graduate education and providing administrative supplements to T32 predoctoral training grants to enhance rigor and reproducibility, career development and skills development.

On June 8, 2016, we took another step to encourage such change with the release of a Request for Information (RFI) seeking input on how our institutional predoctoral training grants program can be used to promote innovations in training. The RFI asked members of the community to weigh in on the strengths and weaknesses of the current system, the skills the next generation of graduate students should acquire, barriers to change and strategies to promote change through our institutional predoctoral research training grants.

We received 90 unique responses from stakeholders ranging from students and faculty to institutions and professional societies. Themes represented in the responses were organized around five major categories:

  • Institutional and training-related issues,
  • Skills development,
  • Systemic issues within the research enterprise,
  • Careers, and
  • Administrative and review issues.

Figure 1. Major Categories in Graduate Education RFI Responses. Bar chart showing the number of RFI responses in which one of the major categories was represented. A total of 90 unique responses were received for the RFI.

While NIGMS recognizes that those who responded to the RFI are unlikely to represent a random subset of the individuals and organizations who have a stake in graduate biomedical education, these responses provide insights regarding how members of the extramural community view the current challenges and opportunities in graduate biomedical education. As such, these comments will inform NIGMS’ ongoing efforts to catalyze the modernization of graduate education through a new predoctoral T32 funding announcement, which is currently under development. For more details about the analysis, we encourage you to explore the report.

Drug Design Data Resource: A Community Participation Project

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If you develop or use software for structure-based drug design or generate data on drug target structures and ligand affinities, you may be interested in the Drug Design Data Resource (D3R) Link to external website. This is an NIGMS-funded project to collect and share high-quality protein-ligand data sets, develop computer-aided drug design workflows, and engage the community through blind prediction challenges.

The D3R, hosted by the University of California, San Diego, continues a program initiated by NIGMS under the Community Structure-Activity Resource (CSAR) at the University of Michigan. A goal of this program has been to gather previously unpublished data from the pharmaceutical industry and other sources and to make it available for validating and improving software for predicting ligand poses and interaction energies. Several data sets have already been donated by companies, including Genentech, AbbVie, GlaxoSmithKline, and Vertex, as well as by academic groups. Both resources have also generated data sets internally or in collaboration with academia.

The data sets, which contain X-ray crystal structures of protein-ligand complexes and structure/activity data for multiple series of ligands, represent 13 different drug targets, including most recently for HSP90, MAP4K4, and designed steroid and vitamin D binding proteins. D3R has also collected data on host-guest systems and made this data available as part of the SAMPL Link to external website series of challenges for benchmarking software predictions of “simple” small-molecule chemical properties such as solvation free energy, partition coefficients, and binding to hydrophobic cavities.

Building on the success of its 1st Annual D3R Workshop Link to external website, in which the 2015 Grand Challenge Link to external website was discussed and summarized in a report, D3R just announced the 2016 Grand Challenge Link to external website. It is based on structures of the Farnesoid X receptor (FXR) and runs through February 2, 2017.

The resource also has developed a Continuous Evaluation of Ligand Pose Prediction Link to external website (CELPP) series of tests in collaboration with the World Wide Protein Databank Link to external website (wwPDB) and the Research Collaboratory for Structural Bioinformatics Link to external website (RCSB), another resource supported by NIGMS. The CELPP tests, which are distinct from the Grand Challenge, will provide chemical compound identifiers of bound small molecules in addition to the protein polymer sequence five days before release of 3D coordinates, giving developers an opportunity to predict docked poses each week.

D3R and its predecessor CSAR were developed to meet the needs of the drug design community identified during workshops several years ago. Continued community input and participation, including additional data donations, are important to help D3R fulfill its mission. Data releases can be coordinated with publication in other formats and venues. Contact D3R principal investigators Rommie Amaro and/or Michael Gilson or send email to drugdesigndata@gmail.com to see how you can be involved.

More Information About New and Early Stage Investigator MIRA Outcomes

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There has been ongoing discussion—both here and in the general scientific community—related to the first MIRA awards to New and Early Stage Investigators (NI/ESI). One question that arose was why applications were administratively withdrawn. Both the NIH Center for Scientific Review and multiple NIGMS staff members, including the program director with a portfolio of grants closest to the applicant’s area of science, screened the applications. Of the withdrawn applications, a majority (~80%) were returned prior to review because they proposed research that fell outside of the NIGMS mission. Others were withdrawn because the applicant was not eligible for the FOA. After review, some applications were withdrawn because the PI accepted another award that was mutually exclusive with the MIRA. As recommended on the MIRA website and elsewhere, we encourage anyone who intends to apply for the Early Stage Investigator MIRA to discuss their plans with the appropriate NIGMS program director to determine whether the proposed research area is within the mission of the Institute and if the applicant is eligible to apply.

A major NIGMS goal is to support a broad portfolio that is diverse in research topics, approaches, institutions and investigators. This means we are looking carefully at the outcomes of awards, including gender and race/ethnicity data. We are also trying to take proactive steps to prevent bias during the review, for instance by covering the topic as part of reviewer orientations that take place several weeks before the MIRA study sections meet.

In our recent summary of MIRA applicant and awardee demographics, we looked to see how applications from underrepresented groups compared to those from well-represented groups (White and Asian). The p-value for a difference between the distributions of funded and unfunded applications from these groups was 0.63, meaning that there was no statistically significant difference between the two groups. We also compared the MIRA success rates to those of ESI applicants for NIGMS R01s in fiscal years (FY) 2011-2015 (Table 1).

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Trending Young in New and Early Stage Investigator MIRA

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Dr. Jon Lorsch

The MIRA presentation at the September 2016 Advisory Council meeting begins at 17:13.

Following up on the previous post regarding the first MIRA awards to New and Early Stage Investigators, we issued awards to a total of 94 grantees. In addition to ensuring that we are funding the highest quality science across areas associated with NIGMS’ mission, a major goal is to support a broad and diverse portfolio of research topics and investigators. One step in this effort is to make sure that existing skews in the system are not exacerbated during the MIRA selection process. To assess this, we compared the gender, race/ethnicity and age of those MIRA applicants who received an award with those of the applicants who did not receive an award, as well as with New and Early Stage Investigators who received competitive R01 awards in Fiscal Year (FY) 2015.

We did not observe any significant differences in the gender or race/ethnicity distributions of the MIRA grantees as compared to the MIRA applicants who did not receive an award. Both groups were roughly 25% female and included ≤10% of underrepresented racial/ethnic groups. These proportions were also not significantly different from those of the new and early stage R01 grantees. Thus although the MIRA selection process did not yet enhance these aspects of the diversity of the awardee pool relative to the other groups of grantees, it also did not exacerbate the existing skewed distribution.

We did observe significant differences among the mean ages of the MIRA grantees, MIRA applicants who did not receive an award and the R01-funded grantees. The MIRA grantees are 1.5 years younger on average than those MIRA applicants who did not receive an award (37.2 vs. 38.7 years, p<0.05), and about 2 years younger than the FY 2015 R01-funded Early Stage Investigators (37.2 vs. 39.1 years, p<0.001). The R01-funded New Investigators in FY 2015, a pool which includes a few individuals older than 60 years, average an age of 45.6 years. This selection for funding investigators earlier is a promising feature of the first round of MIRA awards to New and Early Stage Investigators. As noted at the recent meeting of our Advisory Council, where Jon presented these data, 37 years is still relatively late for investigators to be getting their first major NIH grant. We will continue to monitor this issue with the goal of further decreasing that figure.

Final FOA for NIGMS Program Project Grants

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We have reissued a funding opportunity announcement (FOA) for program project grants (P01) in areas related to NIGMS’ mission. The program remains unchanged from the previous FOA. The next application deadline is January 25, 2017. The program project grant is designed to support research in which the funding of several interdependent projects offers significant scientific advantages over the support of these same projects as individual regular research grants.

We’re exploring alternative approaches to fund team science projects. We recently requested community input on this topic. The responses we received included a recommendation to support interdisciplinary, challenging science beyond multiple-PI R01s that would allow greater flexibility than what is possible with the existing P01 program. We’ll keep you posted on our plans.

Upcoming NIGMS Job Vacancy for a Biomedical Technology Program Director

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UPDATE: The two vacancy announcements for this position are now available on USAJOBS: one is for candidates with current and former federal employment status and the other is for candidates without such status.

We’re looking for a program director with expertise in the development and application of advanced technologies for biomedical research. This individual will manage grant programs that support technology development, as well as access to research resources.

The position is located in the Biomedical Technology Branch of our Division of Biomedical Technology, Bioinformatics, and Computational Biology. Expertise in the following areas is of particular interest: structural biology technologies covering X-ray methods, including macromolecular crystallography, scattering, and spectroscopy and cryo-electron microscopy methods, including single particle, tomographic and micro-electron diffraction applications; and bioanalytical technologies, including mass spectrometry, separations and protein chemistry.

Candidates should have strong oral and written communication skills. Familiarity with NIH extramural funding as a grant applicant, reviewer or NIH scientific administrator is a plus.

The vacancy, which is part of an NIH-wide global announcement, will be available on USAJOBS  on October 3 and will close on October 12. In the meantime, a description of the position is posted on the NIGMS Job Vacancies page. Previous blog posts on Applying for Scientific Administration Jobs at NIGMS and Scientific Careers in the Federal Government offer additional background and tips.

If you have any questions about the position, please contact me. If you have questions about NIGMS or this hiring process, contact Claudia Gonzalez. I’d appreciate it if you would share this upcoming job announcement with individuals who may be interested in this opportunity.

Moving Further Afield

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In recent talks for iBiology Link to external website and TEDx Link to external website, NIGMS grantee Alejandro Sánchez Alvarado proposes that because so much of biomedical research focuses on only a handful of model organisms we are limiting our knowledge of biology. He suggests that many important discoveries lie waiting in species that have not yet been the subjects of sufficient investigation. This is a topic of interest to us as well; in fact, Dorit Zuk, director of our Division of Genetics and Developmental Biology, is currently leading an internal working group that’s examining the varied landscape of organisms studied by NIGMS grantees and the new scientific questions that could be answered using a diversity of organisms. We’ll be discussing these topics in future posts.

In addition to the number of organisms we study, other aspects of the biomedical research system may be limiting the breadth of our knowledge. For example, does the expectation that junior faculty work on a problem closely related to their postdoctoral research constrain our explorations to “islands” of study, leaving vast areas under- or unexplored?

The forces keeping biomedical junior faculty within their postdoctoral research areas include the expectations of faculty search committees, grant review panels and funding agencies, as well as the promotion policies of academic institutions. Interestingly, in the chemical sciences, junior faculty are usually expected to develop projects that are distinct from their postdoctoral work, which often involves moving into completely new areas of study. Why the sociology of chemistry evolved so differently in this regard from other fields related to biomedical research is an interesting question.

Should the biomedical research enterprise change its expectations to empower junior researchers to move further away from their postdoctoral work when they start their independent research careers? Would this accelerate the pace of discovery? New programs such as the Maximizing Investigators’ Research Awards (MIRA) for Early Stage Investigators give us an opportunity to revise our expectations for researchers at the beginning of their independent careers. Would this be desirable? What might we look for in assessing outcomes? If we, as funders, successfully made such a change in expectations, would the rest of the research ecosystem make parallel changes to support efforts by junior scientists to leave their home “islands” and move into new territory?

I would be interested to hear your thoughts on these questions.