Nobel Prize in Chemistry - 2008

Shared Nobel Prize in Chemistry Goes to Co-Investigator at NCRR Biomedical Technology Research Center

One of three scientists to receive the prize, Dr. Roger Tsien is a co-investigator of the NCRR-supported National Center for Microscopy Imaging Research

On October 8, 2008, Dr. Roger Y. Tsien of the University of California San Diego, along with two other scientists, Osamu Shimomura of the Marine Biological Laboratory in Woods Hole and Boston University School of Medicine, and Martin Chalfie of Columbia University in New York, received the Nobel Prize in Chemistry for their discovery of the green fluorescent protein, GFP, and its development as a tool for observing otherwise invisible cellular processes. The brightly fluorescent GFP can be attached to other proteins within a cell, thereby serving as a location marker of the proteins to which it has been attached. This has given insight into complicated cellular structures and processes.

In announcing the award, the Royal Swedish Academy of Sciences said that "the green fluorescent protein was first observed in the beautiful jellyfish, Aequorea victoria in 1962. Since then, this protein has become one of the most important tools used in contemporary bioscience."

Dr. Tsien was recognized, in part, for extending "the colour palette beyond green allowing researchers to give various proteins and cells different colours. This enables scientists to follow several different biological processes at the same time."

Dr. Tsien is a Co- Investigator on the National Center for Microscopy Imaging Research (NCMIR) grant, a NCRR-supported Biomedical Technology Research Center which is directed by Dr. Mark Ellisman at the University of California San Diego. Dr. Tsien's work has been critical to the capabilities of the center where so many of the images using Tsien's colorful molecular probes have been generated and where biomedical researchers come to learn how to apply the latest of these advanced labeling technologies.

Photo: Figure Caption Golgi twins in late mitosis. Different stages of mitosis can be seen in HeLa cells expressing the Golgi marker (green) and stained for microtubules (red) and DNA (blue). Insert (bottom right): Dynamic imaging of the Golgi apparatus during mitosis using fluorescence microscopy. The cells were fixed when the four Golgi twins were formed and analyzed by correlated electron microscopy (magnifying glass at upper right). Download Photo (526KB JPG)

Dr. Tsien pioneered the tetracysteine-biarsenical method of specifically labeling proteins of interest within the cell with smaller fluorescent probes that don't have the size limitations of the relatively large GFP. This approach allows for viewing the proteins of interest in a live cell using light microscopy, which can reveal the changing locations of the color-tagged proteins during a living process. After a chemical adjustment to the fluorescent tag so it can be visible by electron microscopy as well, the same cell can be viewed at much higher resolution, revealing exquisite details invisible in the light microscope. Tsien is a leader in the development of new indicator systems and their application to cell biology and has been a driving force behind the NCMIR core efforts to develop improved labeling technologies and imaging instruments for correlative light and electron microscopy.

Dr. Tsien's fluorescent probes have served a critical role on numerous research projects. Recently, Tsien and his NCMIR colleagues demonstrated a powerful new approach for observing the complex dynamics of the Golgi apparatus — the organelle responsible for correctly sorting, targeting, and trafficking protein in human cells. Understanding how the Golgi functions is important as this organelle may be linked to Alzheimer's disease and a host of other protein and lipid storage diseases that are likely brought about by the effects of incorrectly sorting proteins and lipids in cells.

Familiar with the intrinsic difficulties that have limited previous studies of the Golgi, the research team designed a molecular probe optimized for correlated light and electron microscopic analysis and fused it to a specific Golgi-resident protein. The fluorescent portion of the probe permitted the researchers to use light microscopy to trace the breakup and subsequent reassembly of the Golgi apparatus in living cells throughout mitosis. Using time-lapse live-cell imaging, the research team traced the dynamics of the Golgi apparatus through the cycle of cell growth and cell division. Following photoconversion of the same Golgi tag for correlated high-resolution electron microscopy, the team precisely located the Golgi proteins with high resolution, revealing the unexpected result that elements of the Golgi complex remained distinct throughout the cell's life cycle and that as celsl exit cell division, there are for a short time two Golgi bodies in each cell on opposite sides of the cell nucleus. These findings and the powerful methods applied have implications and provide new approaches that may help hasten our understanding of the most fundamental processes underlying cell division and the cellularization of specific organs.

The National Center for Microscopy and Imaging Research (NCMIR) at the University of California San Diego develops state-of-the-art 3D imaging and analysis technologies to help biomedical researchers understand biological structure and function relationships in cells and tissues in the dimensional range between 5 nm3 and 50 µm3.

The Biomedical Technology Research Centers Program supports (via the P41 funding mechanism) specialized centers that develop new technologies, create opportunities for collaborative research, and provide access to a broad spectrum of technologies, techniques, and methodologies to this nation's biomedical research community.