We congratulate long-time NIGMS grantee Peter Walter of the University of California, San Francisco, on being recognized with the 2014 Albert Lasker Basic Medical Research Award for his elegant and insightful work on the signal that activates the unfolded protein response (UPR). He shares the honor with Kazutoshi Mori of Kyoto University in Japan.
For more than 30 years, we have funded the Walter lab to investigate how yeast cells control the quality of their proteins and organelles to maintain homeostasis. In the 1990s, at the time Walter was conducting the research that led to this award, we supported his studies of protein translocation and the signal recognition particle, which links the nascent protein chain to the endoplasmic reticulum, where folding then occurs. This work led, in part, to his research on the downstream events associated with protein misfolding and his identification of the key signal that activates the UPR.
The UPR mechanism adjusts as needed to maintain normal cellular function and prevent disease. Sustained overactivation of the UPR has been implicated in cancer, diabetes, autoimmune conditions, liver disorders and neurodegenerative diseases. Additional studies have shown that the UPR is highly conserved and present in every cell.
The Lasker Award to Walter, who’s also an HHMI investigator, is a strong endorsement of question-driven basic research and its role in revealing unpredicted, medically important pathways.
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 .
Jim Deatherage contributed to this post.