Roger Y. Tsien
Roger Y. Tsien was an influential American biochemist renowned for his groundbreaking contributions to the field of fluorescent protein research, particularly the development and application of green fluorescent protein (GFP). Born in New York City in 1952 and raised in New Jersey, Tsien displayed an early fascination with chemistry, which led him to pursue higher education in the sciences. He earned a bachelor's degree from Harvard University and a PhD from Cambridge University, focusing on neuroscience and molecular biology.
Tsien's academic career began at the University of California, Berkeley, and later moved to the University of California, San Diego, where he made significant advancements in using GFP to visualize biological processes in living cells. His work enabled researchers to track proteins and cellular dynamics with unprecedented clarity, impacting areas such as genetics, cell biology, and drug development.
In recognition of his pivotal role in the discovery and enhancement of GFP, Tsien was awarded the Nobel Prize in Chemistry in 2008. His innovations not only transformed biological imaging techniques but also advanced science education by making complex biological processes more accessible through GFP-based demonstrations. Tsien's legacy continues to influence scientific research and education, underscoring the importance of his contributions to modern biology before his untimely passing in 2016.
Subject Terms
Roger Y. Tsien
- Born: February 1, 1952
- Birthplace: New York City, New York
- Died: August 24, 2016
- Place of death: Eugene, Oregon
Scientist
A pioneer in biological imaging, Roger Tsien characterized and exploited green fluorescent protein from jellyfish as an agent for visualizing biological processes within living cells. Tsien’s ingenious use of the protein and its variants revolutionized the ability of scientists to visualize a broad range of biological processes that were thought to be beyond imaging technologies.
Full name: Roger Yonchien Tsien
Also known as: Qian Yongjian
Area of achievement: Science
Early Life
Roger Yonchien Tsien was born in New York City to Hsue Chu Tsien, a prominent engineer who had worked as a liaison officer for the Chinese government and several American companies, and Yi Ying Tsien, who had trained as a nurse. He grew up in Livingston, New Jersey, the youngest of three boys. Tsien’s earliest memories are of his fascination with building sand paths and bridges. Because he suffered from asthma, Tsien had to spend a great deal of time indoors, so his parents bought him a chemistry set, which he used to make colored crystals of metal silicates and solutions of potassium permanganate that changed colors when filtered through paper. These experiments cultivated a lifelong preoccupation with colors.
Tsien attended Livingston High School, where he was frequently bored. In 1967, he spent the summer at Ohio State University in the laboratory of Robert Kline, examining the binding of metals to thiocyanate. The next summer, when he was sixteen years old, he won first prize in the nationwide Westinghouse Talent Search for this work.
With the help of a National Merit Scholarship, Tsien matriculated at Harvard University in the fall of 1968. The dullness of his chemistry classes caused him to search for a new focus, and he became entranced by neuroscience. In 1972, at age twenty, Tsien graduated from Harvard with a bachelor’s degree in chemistry and physics. In order to continue his study of neuroscience, he won a Marshall Scholarship to Cambridge University, where he worked with Jeremy Sanders on the design of small molecules that could detect calcium ion changes in nerve cells. He received a PhD in physiology from Churchill College, Cambridge in 1977 and remained as a research fellow at Gonville and Caius College, Cambridge from 1977 to 1981. During this time, he met his wife, Wendy.
Life’s Work
In 1982, Tsien received an appointment to the Department of Physiology-Anatomy at the University of California, Berkeley. Despite a cut in funds, he was able to make some significant achievements, developing synthetic dyes for calcium ions and sodium. In 1989, he left Berkeley for the University of California, San Diego, where he was given funding from the Howard Hughes Medical Institute, more space, and a dual appointment in the chemistry and biology departments to facilitate his research interests, which lay in a combination of these two fields.
Tsien’s ultimate goal was to express genes in cells that had fluorescent molecules attached to them. This would allow scientists to observe the appearance and movement of proteins in single living cells. The problem was finding a molecule that could be engineered directly into the gene that encodes the protein of interest. In 1992, green fluorescent protein (GFP) was discovered in the marine jellyfish Aequorea victoria by Douglas Prasher and his colleagues at Woods Hole Oceanographic Institute. The instant he read about this protein, Tsien knew that he had found the fluorescent molecule that would do what he wanted.
In Tsien’s laboratory, researcher Roger Heim and his coworkers identified the color-emitting (chromophore) portion of GFP and worked out the enzyme-free, oxygen-dependent mechanism by which the chromophore is constructed inside cells. Heim also isolated several mutants of GFP that glow more intensely and emit different colors. In 1995, Mats Ormö and Jim Remington at the University of Oregon solved the crystal structure of mutant GFP, suggesting new ways to engineer GFP to generate a protein that was more stable than the blue version of GFP. These discoveries contributed to Tsien’s own research in the field.
One of Tsien’s greatest aspirations was to use GFP and its sundry variants to image biological processes within living cells. Atushi Miyawaki, a postdoctoral research fellow in Tsien’s lab, used fluorescence resonance energy transfer (FRET), in which an excited GFP molecule transfers its energy to a nearby dye molecule that then fluoresces at a distinct wavelength, to image protein and calcium ion binding in cells. Miyawaki called these calcium-ion-sensing proteins “chameleons,” and the research group used them to image cell signaling and cell division in many different cell types under various conditions.
In 2009, Xiaokun Shu from Tsien’s lab engineered plant molecules called phytochromes to fluoresce in the infrared spectrum. This achievement, in combination with the earlier isolation of a red fluorescent protein from corals in a Moscow aquarium by researchers from the Russian Academy of Sciences, greatly enhanced the ability of fluorescent proteins to function in living cells and emit light at a wide spectrum of colors and frequencies. In 2012, Tsien received an inaugural Golden Goose Award, which honors federally funded research that has had a significant societal impact.
Tsien was able to recover from a debilitating stroke in 2013. By 2016, he and his team had managed to achieve mammalian expression of small ultra-red fluorescent proteins (smURFPs) from a cyanobacterial phycobiliprotein. Shortly after, following the publication of a paper to present this finding, it was reported that Tsien had died unexpectedly on August 24, 2016, while visiting Eugene, Oregon; he was sixty-four years old.
Significance
Roger Y. Tsien won the 2008 Nobel Prize in Chemistry for his work on GFP. His introduction of GFP to biological research caused seismic shifts in biological imaging; in addition to allowing such imaging to be done easily and cheaply, it also vastly increased the applications of fluorescent imaging in general. For example, by fusing GFP to the control regions of various genes, geneticists can easily quantify gene expression. Protein chemists have used GFP fusions to study protein folding and other parameters of protein function. Cell biologists have also used GFP to visualize a range of phenomena, including waves of increased calcium ion concentrations during cell division, activation of receptors in cancer cells, and the entrance of viruses into cells during viral infection. Drug developers have used GFP-protein fusions to screen for drugs that inhibit the formation of amyloid bodies, those protein agglomerations in the brain that are responsible for most of the pathology associated with Alzheimer’s disease. These are just a few of the myriad uses of GFP imaging.
The ease of GFP visualization also made it a prime choice for educational demonstrations. Several science education equipment suppliers now sell GFP-based gene expression kits that illustrate gene expression, protein function, bacterial transformation, and other biological processes through the ingenious use of GFP. Thus Tsien’s discoveries revolutionized not only biological research but also science education.
Bibliography
Chang, Kenneth. "Roger Y. Tsien, Nobel Winner for Use of Glowing Proteins, Dies at 64." The New York Times, 4 Sept. 2016, www.nytimes.com/2016/09/05/science/roger-y-tsien-nobel-winner-for-use-of-glowing-proteins-dies-at-64.html. Accessed 27 Oct. 2017.
Tsien, Roger Y. “Roger Y. Tsien—Biographical.” Nobelprize.org, Nobel Media, 2008, www.nobelprize.org/nobel‗prizes/chemistry/laureates/2008/tsien-bio.html. Accessed 27 Oct. 2017. An extensive overview of Tsien’s life, including his childhood and the development of his research.
Tsien, Roger Y. “The Green Fluorescent Protein.” Annual Review of Biochemistry, vol. 67, no. 1, 1998, pp. 509–44. A technical summary of the work on GFP that won Tsien the Nobel Prize.
Tsien, Roger Y. “Molecular Designer: An Interview with Roger Y. Tsien.” Interview by Steven Adler. A Passion for Ideas: How Innovators Create the New and Shape Our World, edited by Heinrich von Pierer and Bolko von Oetinger, Purdue UP, 2002, pp. 133–50. Discusses specific aspects of Tsien’s work, education, and approach to research.
Zimmer, Marc. Glowing Genes: A Revolution in Biotechnology. Prometheus, 2005. An introduction to new advances in biotechnology, highlighting many usages of GFP in the field.