MBI’s Professor Sheetz wins Albert Lasker Basic Medical Research Award
The MBI community congratulates Michael Sheetz upon winning the prestigious Albert Lasker Basic Medical Research Award. Michael Sheetz, Director of the Mechanobiology Institute, Singapore, Distinguished Professor of the Department of Biological Sciences, NUS and William R Kenan, Junior Professor at Columbia University, shares this award with two of his collaborators, James Spudich (Stanford University) and Ronald Vale (University of California, San Francisco). The Award was presented at a ceremony on Friday, September 21, 2012, in New York City.
The Albert Lasker Basic Medical Research Award was given to Prof Sheetz, Prof Spudich and Prof Vale in honor of seminal contributions made in establishing methods to study cytoskeletal motor proteins. These developments paved the way to study molecular motors and enabled the discovery of the motor protein, kinesin. The landmark achievements in deciphering new components of cellular motors, which helped explain how these motors worked, were pivotal in understanding the basic fundamental process of energy conversion within the cell. These have led to explorations of these physiologically relevant molecules, as potential drug targets in a variety of disease conditions.
The new players
Many basic cellular functions depend on the directed movement of cytoplasmic organelles, macromolecules, membranes or chromosomes from one place to another within the cell. The transport of this intracellular cargo is achieved by molecular motor proteins, such as myosin and kinesin, which provide force and movement through the conversion of chemical energy (ATP) into mechanical energy. Molecular motor proteins move along scaffolds made of specific protein polymers, with kinesins moving along microtubules and myosins along actin filaments, in order to carry their cargo to the appropriate destination within the cell.
Michael Sheetz and colleagues, Ronald Vale and Thomas Reese, carried out pivotal experiments that ultimately led to the discovery of kinesins, a novel and hitherto unknown family of motor proteins. These experiments involved the development of an in vitro motility assay, whereby proteins from the cytoplasm of neuronal cells were shown to power the movement of microtubules across the surface of glass coverslips. This technique was found to be a sensitive and rapid assay for testing the activity of kinesin and was adopted by numerous labs following these crucial initial experiments.
Subsequently, Sheetz and Spudich worked out an in-vitro method for visualizing actin filaments creeping along myosin coated surfaces, and this system still remains the gold-standard assay for studying myosin movement. With a read-out in hand, many details of the mechanism of action of the motor molecules within the cell were worked out.
For more details of the award winning contribution towards understanding the basics of cellular machinery, please go to http://www.laskerfoundation.org/media/index.htm and also http://www.laskerfoundation.org/media/pdf/2012citation_basic.pdf
A new concept
Michael Sheetz, along with James Spudich and Ronald Vale strongly believe in an open culture of scientific exchange. ‘The most interesting scientific insights result from collaborative, interdisciplinary adventures’, has been the one common theme of Michael Sheetz career. A firm believer of an open laboratory concept where students from different labs and backgrounds, share bench space and often ideas, he emulated the Open Lab model (learn more about MBI’s open labs) at the Mechanobiology Institute, Singapore. This new model of open laboratory environment in interdisciplinary institutes provides an excellent way to encourage fast paced discovery process.
“My greatest excitement comes from considering the puzzle provided by an unexpected result when new technology is applied to an old problem, says Professor Sheetz.„
In his acceptance essay, which can be read here (PDF), Michael Sheetz refers to the importance of collaborations, where the parties are learning from each other and also ‘encourages young scientists to perform speculative experiments whenever they have such an idea, even if most of them fail; since an experiment, even a flawed on, can reveal the solution to an important problem’.
The research in Michael Sheetz’s laboratory continues to explore how mechanical forces are transduced by cells and the molecular processes underlying the mechanisms of cell motility. These general problems are being examined through subcellular analyses of force effects on the dynamics of membranes and the cytoskeleton, using nanofabricated devices.
The answers to these questions will be critical in understanding stem cell differentiation, cancer metastasis and the immune response.
Further to Prof Sheetz’s vital role in developing the in vitro assay that catalyzed the discovery of the kinesins, he has made numerous contributions to the field of single molecule biochemistry. These research efforts have resulted in over 21,000 citations of his work, with two seminal papers being cited over 1000 times each (Sheetz and Singer, 1974 on the bilayer couple hypothesis and Vale et al., 1985 on the discovery of kinesin). In addition to receiving the title of Senior Humboldt Fellow, the First Laurens L.M. van Deenan Award and the Wiley Prize in Biomedical Sciences (2012), Prof Sheetz continues to encourage discoveries through both his research efforts at MBI, services to societies and journals and as Editor-in-Chief of the multimedia, educational website, mechanobio.info.
The Lasker Awards are among the most respected science prizes in the world. Since 1945, the Awards Program has recognized the contributions of scientists, physicians, and public servants who have made major advances in the understanding, diagnosis, treatment, cure, and prevention of human disease. The Lasker Awards often presage future recognition by the Nobel committee, so they have become popularly known as “America’s Nobels.” Eighty-one Lasker laureates have received the Nobel Prize, including 29 in the last two decades.
The Albert Lasker Basic Medical Research Award honors scientists whose fundamental investigations have provided techniques, information, or concepts contributing to the elimination of major causes of disability and death.
By Srivani Sistla