High-Resolution Excitement at the 25th AIDS-Related Structural Biology Meeting

HIV Poster. Image copyright David S. Goodsell, RCSB PDB, www.pdb.org

Image copyright David S. Goodsell, RCSB PDB, www.pdb.org

An exceptional array of structural biologists, cell biologists, virologists and other researchers gathered at NIH late last month to discuss achievements, applications and future directions in AIDS-related structural biology. The group was attending the 25th Annual Meeting of the Groups Studying the Structures of AIDS-Related Systems and Their Application to Targeted Drug Design.

I was extraordinarily impressed by the quality of the science, the passion with which it was presented and the interactive culture of the community.

The meeting began with a keynote address by Steve Harrison of Harvard Medical School. He provided valuable historical perspective and then outlined major challenges facing the field. Two days later, the event concluded with a provocative talk by Manuel Navia of Oxford Bioscience Partners about the economics of bringing new lead compounds through the drug development pipeline.

In between were sessions on the HIV life cycle, HIV host-pathogen interactions, imaging, latency, viral host recognition and structure-based drug design and resistance. There were also lively poster sessions showcasing more than 70 projects.

Approximately 2.8% of the NIGMS budget supports research related to AIDS, which includes individual grants, program projects, centers and institutional training grants.

A major focus of our current AIDS-related structural biology efforts is three P50 Centers for the Determination of Structures of HIV/Host Complexes. With cofunding from the National Institute of Allergy and Infectious Diseases, we support the Center for HIV Protein Interactions Exit icon at the University of Pittsburgh; the Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV Exit icon at the University of Utah; and the HIV Accessory and Regulatory Complexes Exit icon Center at the University of California, San Francisco. These centers use a comprehensive, collaborative approach that engages the larger biological community involved in HIV-cell complex research.

Because the funding initiative for the P50 centers expires next year, we solicited feedback on the program from meeting attendees. We also asked them about emerging scientific opportunities in the field and the best way to move forward. We welcome your input on these topics, too. We’ll talk more about future of NIGMS AIDS-related funding opportunity announcements at the May 2011 meeting of the National Advisory General Medical Sciences Council.

Although many scientific questions remain, the 25th anniversary meeting underscored how basic research on the structure of HIV-1 and interacting host proteins has significantly increased our understanding of virus biology and informed structure-based therapeutic approaches.

The Advisory Council’s Critical Roles

Later this month, the National Advisory General Medical Sciences Council will hold the first of its three meetings in 2011. While many applicants, grantees and reviewers are familiar with the roles and processes of study sections, fewer know how an advisory council works. In this post, I’ll provide an overview of its many critical roles.

Council members are leaders in the biological and medical sciences, education, health care and public affairs. Their areas of expertise cover the broad range of scientific fields supported by NIGMS. The Council performs the second level of peer review for research and research training grant applications assigned to NIGMS. Council members also offer advice and recommendations on policy and program development, program implementation, evaluation and other matters of significance to the mission and goals of the Institute.

A portion of each Council meeting is open to the public.

For the peer review function, which occurs during the part of the meeting that is closed to the public, Council members read summary statements, providing a general check on the quality of the first level of peer review. They advise us if they find cases where the comments and scores do not appear to be in good alignment. Their evaluation complements the initial peer review done by study sections, as it focuses primarily on summary statements rather than on applications (although Council members may have access to the applications).

Members also provide advice regarding formal appeals, typically discussing 10-20 cases per meeting in which a procedural aspect may have significantly influenced the initial peer review process.

The Council also provides input on cases where staff are considering exceptions to the well-funded laboratory policy, and it approves the potential funding of grants to investigators at foreign institutions. Another area of Council input relates to Method to Extend Research in Time (MERIT) awards. Finally, Council members point out applications that they feel are particularly interesting based on their scientific expertise and knowledge of trends in particular fields. They explain their perspective to NIGMS staff, who incorporate this input in subsequent steps of the funding decision process. I’ll describe these steps in an upcoming post.

The policy and program advisory function includes discussing “concept clearances,” or ideas for new initiatives being considered within the Institute. These can take the form of proposed requests for applications (RFAs) or program announcements (PAs). Council members provide critical analysis and feedback about the appropriateness of proposed initiatives and factors to consider should they be implemented. Approved concept clearances are posted soon after each Council meeting on the NIGMS Web site and often on the Feedback Loop. NIGMS staff can then receive input from the scientific community as they refine the funding opportunity announcements.

This month’s meeting will include one concept clearance presentation, on macromolecular complexes.

Council members also give input and feedback on assessments and formal evaluations of specific NIGMS programs, such as the Protein Structure Initiative. When the need arises, Council members form working groups focused on specific issues. To ensure an appropriate range of expertise and perspectives, these groups can include non-Council members, as well. Finally, the Council receives periodic reports about ongoing initiatives in order to monitor how they are proceeding and offer advice about possible changes.

PSI Tools for Your Lab

Short articles summarizing PSI tools and technologiesOver the course of its 10-year existence, the Protein Structure Initiative has supported the development of new technologies and methods that improve the throughput of protein structure determination. Many of them apply to the production of purified proteins for functional and structural studies, and you don’t need access to major research centers to use them.

To help you take advantage of these resources, the PSI Structural Biology Knowledgebase Exit icon offers a series of short articles summarizing tools and technologies developed by PSI-supported investigators. You may also request plasmid clones via the PSI Materials Repository Exit icon.

As always, you can nominate targets Exit icon for PSI investigators to solve.

If you’re going to the 2011 American Crystallographic Association meeting Exit icon (May 28-June 2 in New Orleans) and want to know more about using these PSI products in your own lab, plan on attending my session, “PSI Tools for the Home Lab.” Also, the Structural Biology Knowledgebase will offer workshops at the International Conference of Structural Genomics Exit icon (May 10-14 in Toronto).

Register for 25th Annual NIGMS AIDS-Related Structural Biology Meeting

X-ray structure of hexameric HIV-1 CA (PDB entry 3H47)

Registration is now open for the 25th Annual Meeting of the Groups Studying the Structures of AIDS-Related Systems and Their Application to Targeted Drug Design. The meeting will take place March 28-30, 2011, on the NIH campus in Bethesda.

Plenary sessions will cover the HIV life cycle, host-pathogen interactions, imaging, latency, viral host recognition and structure-based drug design and resistance. The first two days will also include afternoon poster sessions and breakout discussion groups on the future of NIGMS AIDS research initiatives.

Principal investigators, postdoctoral fellows and students are welcome to attend. The meeting is free and open to the public, but advance registration is required. If you’d like to submit a poster presentation, please check the speaker box on the meeting registration page and e-mail me.

The focus of NIGMS-supported HIV studies has evolved from determining the structures of AIDS-related proteins and developing structure-based drug design techniques to identifying mechanisms of drug resistance and host proteins related to the HIV life cycle.

During this special anniversary meeting, the community will have an opportunity to reflect on past accomplishments, describe current advances and develop ideas for future NIGMS AIDS-related funding opportunities. Please visit the meeting Web site for more details about the agenda and confirmed speakers.

We hope to see you in March!

Cell Biology Celebration

The American Society for Cell Biology 50th Annual MeetingCell biologists, including many of our funded investigators and a few of us from NIGMS, were in a celebratory mood as the 50th Annual Meeting of the American Society for Cell Biology Exit icon kicked off December 11 at the Philadelphia Convention Center. The keynote symposium began with Gary Borisy’s description of the first ASCB meeting, when Hans Ris described his then-heretical finding that chloroplasts contain DNA. For more details about the genesis and early years of the ASCB, check out John Fleishman’s article, A Place of Our Own, in the December 2010 ASCB Newsletter Exit icon.

An exciting addition to this year’s meeting was the science discussion table format. Eminent researchers sat at tables for an hour at the beginning of each poster session and took questions from relative newcomers to the field. I stopped by to say hello to some of the NIGMS-supported investigators in my grant portfolio, but each table was crowded with graduate students and postdocs eager to discuss science and seek advice from their fields’ leaders. Two thoughts came to mind as I watched the scene unfold: I wish that there had been these tables when I was a young scientist, and I hope this format becomes a regular feature of the ASCB meeting.

While science is the major focus of the ASCB meeting, education, mentoring and career development also are important features. A number of education workshops focused on topics such as pedagogy, science literacy and online teaching resources. Women in Cell Biology-sponsored events focused on careers, mentoring and managing life as a scientist. In addition, NIH program and review staff answered questions about the grant process. I was one of them, and my favorite part was talking to postdocs and investigators I know from phone calls and e-mail exchanges.

I saw a number of outstanding talks and posters at the meeting, and to say that there is not enough room here to mention them all is an understatement. I was particularly intrigued by presentations from Ron Vale’s lab at University of California, San Francisco, on the cytoplasmic dynein motor domain at 6 Å resolution and from Tom Schwarz at Harvard Medical School on identifying a role for Parkinson’s disease-associated proteins in the regulation of mitochondrial transport within axons. As someone interested in intracellular transport, both presentations offered answers to long-standing problems in cell biology and provided a launching pad for testing new ideas about how organelles move to specific cellular destinations.

I’m already looking forward to the 2011 meeting in Denver.

The 10th Anniversary of ABRCMS: Preparing Underrepresented Minority Students for Scientific Careers

The 10th Anniversary of ABRCMS: Preparing Underrepresented Minority Students for Scientific Careers

Last week, I had the privilege of giving a keynote address at the 10th Annual Biomedical Research Conference for Minority Students (ABRCMS) Exit icon in Charlotte, North Carolina. The conference, sponsored by NIGMS and organized by NIGMS Council member Cliff Houston, had a record attendance of 3,100, including more than 2,000 students and about 20 NIGMS staff members.

The meeting contributes in two major ways to the goal of a scientific workforce that reflects the diversity of the U.S. population. It provides a forum for promising scientists from underrepresented groups to showcase their talent and knowledge and make important training and career connections. It also gives faculty mentors valuable resources for facilitating their students’ success.

My address was organized around the themes from Randy Pausch’s lecture “Really Achieving Your Childhood Dreams Exit icon,” and it described key events and strategies that facilitated my own path to a career in science. I greatly enjoyed discussing science and career opportunities with many of the students at the poster session and after my talk.

Other keynote speakers at this impressive conference included Neil DeGrasse Tyson, Maya Angelou, NIH Director Francis Collins and NIGMS grantee Carolyn Bertozzi.

Jilliene Mitchell, who staffed the NIGMS exhibit booth and talked to a lot of attendees, writes:

The energy level among the meeting attendees soared through the roof of the Charlotte Convention Center. The undergraduate and graduate students were tremendously enthusiastic about networking, presenting their research, listening to scientific talks and getting advice about their career paths from accomplished scientists. The NIGMS exhibit booth received a lot of traffic, with students lined up to talk about training opportunities and faculty members lined up to discuss their grants.

Throughout the conference, I encountered many students who thanked NIGMS for sponsoring ABRCMS. One postdoc summed it up best when she said, “This is the best career development workshop I’ve been to—it’s huge!”

These video clips I took capture the mood and excitement.

The announcement for next year’s ABRCMS meeting is expected soon, and we will post information here when it is available.

National Festival Put Science in the Spotlight

Supermodels of ScienceMany kids (and adults) learned more about science and technology at the 2-week-long USA Science & Engineering Festival Exit icon this month in Washington, D.C. The event featured hundreds of activities, including performances, workshops, demonstrations, tours of mobile labs and interactive games. A number of these were hosted by NIH, which was also one of the event sponsors, and most of its components. The festival wrapped up last weekend with a grand finale expo on the National Mall.

On Sunday, I helped host the NIGMS booth, where we presented a computer activity called “Supermodels of Science.” It showed how model organisms—from slimy worms to furry mice—help scientists learn more about human health. The kids were most excited about responding to the quiz questions at the end of each segment. They also were very interested in how scientists use GFP to make organisms glow different colors.

Other NIH activities included a musical performance by NIH Director Francis Collins; the National Human Genome Research Institute’s “Strawberry DNA Extraction,” a hands-on lab experiment where visitors used a soapy mixture to remove DNA from mashed strawberries; and the National Institute on Deafness and Other Communication Disorders’ “It’s a Noisy Planet,” where staff increased the volume on an iPod to demonstrate dangerous noise levels.

The festival’s turnout was excellent—about 500,000 people attended the weekend event. The kids were excited about science and eager to learn, and the volunteer staff members were thrilled to teach them about the research we support.

We’ll post the “Supermodels of Science” activity on the NIGMS Web site soon, and you’re welcome to use it in your own educational outreach efforts.

Nominate Your Outstanding Graduate Students to Meet Nobel Laureates

Graduate Student Awards for the Lindau Meeting of Nobel Laureates and Students in Lindau, GermanyIt’s the 1st of October, and there’s a Nobel buzz in the air. We’re eagerly awaiting next week’s prize announcements and hoping to see more of our grantees added to the list.

But we’re also feeling the Nobel excitement in another way: the opening of the nomination process for your graduate students to attend the next Lindau Nobel Laureate Meeting Exit icon. Nominations are due from your universities on November 1.

Through this extraordinary opportunity, the most exceptional young researchers go to Lindau, Germany, to engage with Nobel Laureates and meet their peers from around the globe. The upcoming meeting takes place June 26-July 1, 2011, and will feature Nobel prizewinners from physiology or medicine.

A student from last year’s meeting said, “Lindau is much more than a meeting. It is an experience that will change how you look at science and inspire your career.” Other students have told us that it’s “amazing” and “life-changing,” giving them extensive opportunities to network and have focused discussions with the Nobelists. John Schwab and Ravi Basavappa, NIGMS program directors who accompanied the students in past years, came back from the meeting equally charged up.

You can get a sense of what the excitement is all about by viewing a video about the meeting Exit icon.

If you would like to nominate one of your students, visit http://www.orau.org/lindau/ Exit icon for details, instructions and forms. Your universities must submit the applications via this Web site by the November 1 deadline.

Please note that your university president or designee can submit only two candidates to be considered for NIH support. Eligible students can be supported by any NIH institute or center, as long as it funds the research the student is involved in or supports the student through a training award. Universities may also submit up to six additional nominations (two to each of the three other sponsors—DOE, ORAU and Mars, Inc.).

The application process has three phases. First, candidates are selected by their universities for consideration by NIH. Second, NIH selects approximately 40 student nominations, which represents more than half of the U.S. delegation. The last phase is conducted by the Lindau Meeting. Selection is a highly competitive process, and we’re counting on you to identify the best candidates to represent U.S. science next year!

The Value of Attending SACNAS and ABRCMS

SACNAS National ConferenceThis fall, NIGMS will be sponsoring the Society for Advancement of Chicanos and Native Americans in Science (SACNAS) national conference in Anaheim, CA, September 30-October 3, and the Annual Biomedical Research Conference for Minority Students (ABRCMS) in Charlotte, NC, November 10-13.

ABRCMS Seal

These meetings present two wonderful opportunities for you to meet and recruit science-oriented undergraduate students from groups that are underrepresented in the biomedical sciences. In addition to listening to research talks, you can volunteer to mentor students during the meeting or judge their posters. For those of you who are MORE program directors, you’ll also be able to support your students.

I encourage you to attend one or both of these meetings, as they bring in some of the best and brightest undergraduate students in the nation.

You can visit NIGMS staff at SACNAS exhibit booth 817 or ABRCMS exhibit booth 700.

For additional information or to register as a meeting participant, mentor and/or judge, visit the SACNAS Exit icon and ABRCMS Exit icon Web sites.

Model Organisms and the Significance of Significance

I recently had the opportunity to speak at the Model Organisms to Human Biology meeting Exit icon sponsored by the Genetics Society of America. I shared some of my perspectives on the powerful interplay between studies of model organisms and studies of humans (both individuals and populations) enabled through genetics. I illustrated why results over many decades have shown that studying fundamental mechanisms in a wide range of organisms can elucidate important processes relevant to human health and disease.

I also discussed aspects of the NIH peer review system, particularly with regard to proposed studies of model organisms.

One of the key changes in the new peer review system is the use of individual scores for five specific criteria. During my talk, I focused on the significance criterion:

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

This definition is intended to cover the entire range of research supported by NIH, spanning basic studies of fundamental mechanisms through applied studies that have the potential for direct clinical impact.

Some applicants who use model organisms try to explain the significance of their project by making relatively tenuous links to specific clinical areas. As an alternative, they should consider highlighting the study’s importance to a basic field of biomedical or behavioral research and the reason for using a specific experimental system.

To examine how reviewers apply the significance criterion in determining overall impact scores, I analyzed 360 NIGMS R01 applications reviewed during the October 2009 Council round. A plot comparing the average significance scores with the overall impact scores for these applications is shown below.

Plot of significance and overall impact scores in a sample of 360 NIGMS R01 applications reviewed during the October 2009 Council round.

Plot of significance and overall impact scores in a sample of 360 NIGMS R01 applications reviewed during the October 2009 Council round.

As anticipated, the scores are reasonably strongly correlated, with a Pearson correlation coefficient of 0.63. Similar comparisons with the other peer review criteria revealed correlation coefficients of 0.74 for approach, 0.54 for innovation, 0.49 for investigator and 0.37 for environment.

This analysis indicates that approach and significance are the most important factors, on average, in determining the overall impact score, at least for this sample of NIGMS R01 grant applications.

UPDATE: Jeremy Berg has posted similar analyses of the approach and innovation criteria.