NIGMS Feedback Loop Blog – National Institute of General Medical Sciences

Last 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 that will continue to exist as a resource for updates in the field; you can subscribe at http://cellmigration.org/cmg_update/ealert/signup.shtml (no longer available).

Jim Deatherage contributed to this post.

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 at the University of Pittsburgh; the Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV at the University of Utah; and the HIV Accessory and Regulatory Complexes 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.