Register Now for the Protein Data Bank’s 40th Anniversary Symposium

A special symposium marking the 40th anniversary of the Protein Data Bank (PDB) Exit icon will be held this year at Cold Spring Harbor Laboratory in New York, October 28-30.

It’s quite fitting that the meeting is being held here. It was a 1971 symposium at the laboratory titled “The Structure and Function of Proteins at the Three-Dimensional Level” that led to the establishment of the PDB as a freely accessible portal for the experimentally determined structures of biological macromolecules. Since then, the PDB has grown into an international resource for structural biology, today containing nearly 75,000 structures of proteins, nucleic acids and complex assemblies.

Because it is such a vital resource for researchers, NIGMS and other parts of NIH, along with the National Science Foundation and Department of Energy, have helped fund the PDB’s operation for many years. NIGMS is also a sponsor of the symposium.

The October event, which is open to all, will include presentations by many prominent scientists who have been instrumental in the development of the PDB and the field of structural biology. Among the confirmed speakers are Michael Rossmann of Purdue University, an early advocate of the PDB; Wayne Hendrickson of Columbia University, a leader in solving the structures of membrane proteins; and Kurt Wüthrich of the Scripps Research Institute and the ETH Zürich, a pioneer in NMR structure determination techniques.

A limited number of travel awards to attend the symposium are available for students and early career scientists; applications are due by
August 1
.

More information about the program, registration and travel is on the meeting Web site.

Meetings Help Develop a Diverse Scientific Workforce

SACNAS National ConferenceAs part of our commitment to developing a diverse scientific workforce, we sponsor the Society for Advancement of Chicanos and Native Americans in Science (SACNAS) national conference Exit icon and the Annual Biomedical Research Conference for Minority Students (ABRCMS) Exit icon.

ABRCMS Seal

These conferences represent two of the largest gatherings of science and math undergraduate students from groups that are underrepresented in the biomedical and behavioral sciences. They are terrific opportunities for you to meet and recruit outstanding students. You also can volunteer to mentor students or judge their posters.

This year, SACNAS will meet in San Jose, CA, October 27-30, and ABRCMS in St. Louis, MO, November 9-12. For more information or to register, visit the meeting Web sites.

Connecting at Lindau

Greetings from Lindau, Germany, where I and my NIH colleagues, Irene Eckstrand and Katrin Eichelberg, are attending the 61st Lindau Nobel Laureate Meeting Exit icon. This year’s meeting, focused on physiology and medicine, has brought together 23 Nobel laureates and 566 outstanding pre- and postdoctoral students, including 80 from the United States, to share their passion for science and their commitment to finding solutions to the world’s biggest problems.

Video remarks from NIH Director Francis Collins at the Lindau meeting.

Video remarks from NIH Director Francis Collins at the Lindau meeting.

This is the third year that NIGMS has participated in the Lindau program, and the first year in which participation was NIH-wide.

Each morning, six Nobel laureates have given short lectures about the history of their science, their successes and failures, and their visions of the future. Among the NIGMS-funded laureates giving these talks are Elizabeth Blackburn, Oliver Smithies, Thomas Steitz, Roger Tsien and Ada Yonath. The afternoons are reserved for free-ranging discussions among the laureates and young researchers. It has been a delight to watch the two groups get to know each other and discuss important scientific problems of global interest and importance.

On the opening day, Countess Bettina Bernadotte, whose family has sponsored the meeting since its beginning, welcomed the assembly. Her enthusiasm for science and her commitment to the meetings was apparent in her introduction of the Lindau mission – “Educate. Inspire. Connect” – and her advice that we “never cease to be curious.” Expanding on this, Annette Schavan, the German Federal Minister of Education and Research, stressed that connections among the generations, such as those made at this meeting, are crucial to scientific progress.

The American delegation, which was sponsored by NIH, the Department of Energy, Oak Ridge Associated Universities and Mars Incorporated, organized a U.S.-themed International Day on Monday, June 27. This series of events truly jumpstarted the week.

As part of International Day, NIH-supported Nobel laureate Peter Agre explained his view of the scientist-citizen who uses his or her knowledge and talents to make the world a better place. The discoverer of aquaporins, Agre talked about applying his research to fighting malaria in Zambia. NIGMS’ Irene Eckstrand then spoke about using the power of computing to inform policies for the control and eradication of infectious diseases. An energetic discussion ensued between the highly engaged students and speakers, focusing on efforts to understand the epidemiology of malaria, approaches to reducing the number of deaths from the disease and the importance of collaborative research between developed and developing nations.

The International Day evening program included a very well-received video address from NIH Director Francis Collins on the strength of American medical science. His message about NIH’s commitment to global health aligned perfectly with the focus of earlier talks, including a presentation by Bill Gates, who was inducted into the Honorary Senate of the Lindau Foundation.

Irene, Katrin and I are all quite proud to have been a part of this effort and look forward to sharing more about our experiences here.

Post written by Donna Krasnewich, Irene Eckstrand and Katrin Eichelberg (NIAID)

At the Interface of Evolution and Medicine

At last week’s Evolution and Medicine Symposium Exit icon at the Evolution 2011 meeting in Norman, Oklahoma, experts from around the country came together to discuss how evolutionary biology is influencing our understanding of human health and disease.

At the meeting, I talked about NIGMS’s commitment to funding research on the principles and dynamics of evolution and highlighted the importance of studying biological systems, such as infectious diseases and physiology, in their evolutionary context.

In preparing my remarks, I realized that the work of clinicians and evolutionary biologists could be highly synergistic. M.D.s know a great deal about individual variation and clinical presentation, while evolutionary biologists have a good grasp of variation at the population level. Both of these perspectives are very valuable to the field of personalized medicine, for example. The question now is: How do we create an opportunity for these two groups to work with each other?

The meeting featured many interesting talks, including:

  • Dyann Wirth of the Harvard School of Public Health explained that in the very near future we will have enough sequence data from Plasmodium, mosquitoes and humans to understand regional variation as well as co-evolution of the malaria pathogen and its hosts. We should be able to use this information to build computational models and evaluate intervention, eradication and elimination strategies. Wirth said these capabilities stem from advances in DNA sequencing technologies that are having a revolutionary effect on evolution research, including evolution and medicine.
  • Carl Bergstrom of the University of Washington spoke on the integration of mathematical modeling and evolution. He gave a real example of how to use antiviral drugs most effectively in an influenza outbreak. The question was how to deploy antivirals to reduce the likelihood of resistance and minimize illness and death. Bergstrom said that the answer is non-obvious unless you understand how phylogenies work and know a little bit of math.
  • Angela Hancock of the University of Chicago talked about recent data showing that human genetic variation that’s adaptive in one context will not be so in other contexts. Studying 61 populations from different parts of the world, she identified signals of selection in a variety of genes related to UV radiation, infection and immunity, and cancer.

This symposium came at the perfect time to describe two new NIGMS-related efforts. We previewed an NIH high school curriculum supplement on evolution and medicine that will be released this fall. Also, in conjunction with the National Science Foundation and the U.S. Department of Agriculture, we will be announcing later this summer a call for applications to study dynamic biological systems in their ecological and evolutionary contexts. I’ll share more details about these efforts in the near future.

Moving Cell Migration Forward: Meeting Highlights Progress

Frontiers in Cell Migration and Mechanotransduction meeting posterLast week, NIGMS hosted the Frontiers in Cell Migration and Mechanotransduction meeting. It brought together an impressive group of scientists working at many levels, from molecules to cells, tissues and organs.

The overall sense from the meeting is that a wide variety of tools, approaches and even fields have converged on this topic of how and why cells move and that this convergence has become a source of collaboration between communities that historically have not interacted.

Several important themes emerged, including:

  • Events, such as cell signaling, are highly localized and closely coordinated. In a fascinating talk, Klaus Hahn (University of North Carolina, Chapel Hill) presented new experimental data using a photoactivable and completely reversible probe that he developed for RhoG. Important in wound healing, RhoG turns on immediately at the leading edge when the cell moves and seems to regulate the direction of cell migration and whether a cell can turn.
  • It’s all about forces—once invisible to most techniques that biologists have used, forces are now being deduced and measured internally. Chris Chen (University of Pennsylvania) showed us a stem cell’s response to the dish surface generates cellular forces and that these forces affect whether the cell rounds up or spreads. Chen’s data suggests that cell spreading is essential for triggering distinct differentiation pathways—and that whether a stem cell becomes a brain or a bone cell is driven by this contractility.
  • Cells communicate and influence each other. In a talk that linked basic biology to clinical research, Anna Huttenlocher (University of Wisconsin-Madison) showed that leukocyte migration can be an immune response to cell wounding. By using photo-caged biosensors developed by Klaus Hahn, she found that neutrophil cells are more active and recruited more quickly after subsequent wounding events. They also recruit other cells to the wound sites.

The talks, as well as the poster session, pointed to additional conclusions: Cell migration is a collective behavior, and feedback mechanisms control many cell migration events.

This was the third and final meeting organized by the NIGMS-funded Cell Migration Consortium (CMC), whose project will sunset in August 2011. The consortium developed a cell migration gateway Exit icon that will continue to exist as a resource for updates in the field; you can subscribe at http://www.cellmigration.org/cmg_update/ealert/signup.shtml Exit icon.

Jim Deatherage contributed to this post.

Fiscal Year 2012 Budget Update

The Senate hearing on the Fiscal Year 2012 President’s budget request for NIH happened on May 11, and you can watch the archived Webcast.

My written testimony and NIH Director Francis Collins’ written testimony on next year’s budget are also now available. The ultimate outcome will be a bill appropriating funds for NIH and its components (view history of NIH appropriations).

For more on the proposed NIGMS budget, see my update from February 15.

Council Tribute to Director Berg

At today’s National Advisory General Medical Sciences Council meeting, member Howard Garrison offered the following statement to Jeremy Berg on behalf of the entire Council:

“In appreciation of your 7 years of leadership at NIGMS, the members of the Council express their profound gratitude to you for your distinguished service to science and the nation. We recognize your outstanding work in the pursuit of excellence in research and education, mentoring and advocacy for basic research. Your willingness to deal directly with challenging issues has earned you our respect and admiration. It has been a pleasure and an honor to work with you, and we will miss you. We wish you continued success in your new endeavors.”

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 (May 10-14 in Toronto).