Roger Yonchien Tsien (born February 1, 1952) is an American biochemist. He is a professor at the Department of Chemistry and Biochemistry, University of California, San Diego. He was awarded the 2008 Nobel Prize in chemistry "for his discovery and development of the green fluorescent protein (GFP) with two other chemists: Martin Chalfie of Columbia University and Osamu Shimomura of Boston University and Marine Biological Laboratory.
Tsien has a number of accomplished engineers in his extended family, including his father Hsue-Chu Tsien who was a MIT graduated mechanical engineer and his mother's brothers Y. T. Li (李耀滋) and Shihying Lee (李诗颖) who were engineering professors at MIT. Tsien's parents Hsue-Chu Tsien and Yi-Ying Li (李懿颖) came from Hangzhou and Beijing, respectively. The famous rocket scientist Tsien Hsue-shen, regarded as the co-founding father of JPL of Caltech and later the director of the Chinese ballistic-missile and space programs, is a cousin of Tsien's father. Tsien's brother Richard Tsien is also a renowned scientist currently at New York University. Tsien, who calls his own work molecular engineering, once said, "I'm doomed by heredity to do this kind of work."
Tsien suffered from asthma as a child, and as a result, he was often indoors. He spent hours conducting chemistry experiments in his basement laboratory. When he was 16, he won first prize in the nationwide Westinghouse talent search with a project investigating how metals bind to thiocyanate.
He attended Harvard University on a National Merit Scholarship, where he was elected to Phi Beta Kappa as a junior. He graduated summa cum laude with a Bachelor of Science in chemistry and physics in 1972. According to his freshman-year roommate, economist and Iowa politician Herman Quirmbach, “It’s probably not an exaggeration to say he’s the smartest person I ever met... [a]nd I have met a lot of brilliant people.”
After completing his bachelor's degree, he joined the Physiological Laboratory at the University of Cambridge in Cambridge, England with the aid of a Marshall Scholarship. He received his PhD in physiology from Churchill College, University of Cambridge in 1977, with the doctoral dissertation The Design and Use of Organic Chemical Tools in Cellular Physiology (1976) supervised by Prof. Jeremy Sanders.
Tsien was a Research Fellow at Gonville and Caius College, University of Cambridge from 1977 to 1981. He was appointed to the faculty at the University of California, Berkeley, from 1982 to 1989. Since 1989 he has been working at the University of California, San Diego, as Professor of Pharmacology and Professor of Chemistry and Biochemistry, and an investigator of the Howard Hughes Medical Institute.
Tsien is renowned for revolutionizing the fields of cell biology and neurobiology by discovering genetically programmable fluorescent tags, thereby allowing scientists to watch the behavior of molecules in living cells in real time. He also developed fluorescent indicators of calcium ions and other ions important in biological processes.
In 2004, Tsien was awarded the Wolf Prize in Medicine "for his seminal contribution to the design and biological application of novel fluorescent and photolabile molecules to analyze and perturb cell signal transduction."
The multicolored fluorescent proteins developed in Tsien's lab are used by scientists to track where and when certain genes are expressed in cells or in whole organisms. Typically, the gene coding for a protein of interest is fused with the gene for a fluorescent protein, which causes the protein of interest to glow inside the cell when the cell is irradiated with ultraviolet light and allows microscopists to track its location in real time. This is such a popular technique that it has added a new dimension to the fields of molecular biology, cell biology, and biochemistry.
Former trainees include Atsushi Miyawaki and Alice Y. Ting.
Timelines of GFP-development involved by Tsien:
- 1994: Tsien showed the mechanism that GFP chromophore is formed in a chemical reaction which requires oxygen but without help from the other proteins.
- 1994–1998: Tsien and collaborators made various GFP mutants by genetic modification and structural tweaking. Newly created variants of GFP can shine more brightly and show different colours, such as yellow, cyan, and blue.
- 2000–2002: Tsien produced monomeric variants of DsRED, which can glow in shades of red, pink, and orange. Remarkably, since then complicated marcromolecular networks of living organisms can be labelled or marked by using "all the colours of the rainbow".
Other detailed highlights involved by Tsien:
- 2002: The critical structural difference between GFP and DsRed was revealed. One extra double-bond in the chromophore of DsRed extends its conjugation thus causes the red-shift.
- 2002: Monomeric DsRed (mRFP) was first developed.
- 2004: New "fruit" FPs were generated (by in vitro and in vivo directed evolutions).
In 2009, a new kind of IFP was developed by Tsien's group, and further reported and described by Science. The new IFPs are developed from bacterial phytochromes instead of from multicellular organism like jellyfish. Under normal conditions, bacterial phytochromes absorb light for signaling instead of fluorescence, but they can be turned fluorescent after deleting some of the signaling parts by genetic means such as site-directed mutagenesis. In order to fluorescence, tetrapyrrole is also required, however, it's abundant in living bodies.
Tsien is a key pioneer of calcium imaging and well known for developing various dyes which become fluorescent in the presence of particular ions such as calcium. One such dye, Fura-2, is widely used to track the movement of calcium within cells. Indo-1, another popular calcium indicator, was also developed by Tsien's group in 1985. He has also developed fluorescent indicators for other bio-relevant ions.
Aequorin is also a useful tool to indicate calcium level inside cells; however, it has some limitations, primarily is that its prosthetic group coelenterazine is consumed irreversibly when emits light, thus requires continuous addition of coelenterazine into the media. To overcome such issues, Tsien's group also developed the calmodulin-based sensor, named Cameleon.
- "FLASH-EDT2": Fluorescein arsenical helix binder, bis-EDT adduct,
- "EDT": 1,2-ethanedithiol.
Fluorescence-assisted cancer surgery
Mouse experiments by Tsien's group suggest that cancer surgery can be guided and assisted by fluorescent peptides. The peptides are used as probes, and are harmless to living tissues and organs. Their lifetime in the body is only 4 or 5 days. Clinical trials are awaited.
Industrial and educational activities
Tsien is also a notable biochemical inventor and holds or co-holds about 100 patents till 2010. In 1996, Tsien co-founded the Aurora Biosciences Corporation, which started its public commerce in 1997. In 2001, Aurora was acquired by the Vertex Pharmaceuticals. Similarly, Tsien was also a scientific co-founder of Senomyx in 1999.
Awards and honors
Roger Y. Tsien has received numerous honors and awards in his life, including:
- National 1st Prize, Westinghouse Science Talent Search (1968)
- National Merit Scholarship, USA (1968)
- Detur Prize, Harvard College (1969)
- Marshall Scholarship, British government (1972)
- Comyns Berkeley Research Fellowship, Gonville and Caius College, Cambridge (1977)
- Gedge Prize, University of Cambridge (1978)
- Searle Scholar, Searle Scholar program (1983)
- Lamport Prize, New York Academy of Sciences (1986)
- Javits Neuroscience Investigator Award, National Institute of Neurological Disorders and Stroke (1989)
- Young Scientist Award, Passano Foundation (1991)
- W. Alden Spencer Award in Neurobiology, Columbia University (1991)
- Artois-Baillet-Latour Health Prize, Belgium (1995)
- Gairdner Foundation International Award, Canada (1995)
- Basic Research Prize, American Heart Association (1995)
- Elected to the United States Institute of Medicine (1995)
- Doctorate honoris causa, Katholieke Universiteit Leuven, Belgium (1995)
- Faculty Research Lecturer, UC San Diego (1997)
- Elected to the American Academy of Arts and Sciences (1998)
- Elected to the United States National Academy of Sciences (1998)
- Award for Innovation in High Throughput Screening, Society for Biomolecular Screening (1998)
- Pearse Prize, Royal Microscopical Society (2000)
- ACS Award for Creative Invention, American Chemical Society (2002)
- Christian B. Anfinsen Award, Protein Society (2002)
- Heineken Prize for Biochemistry and Biophysics, Royal Netherlands Academy of Arts and Sciences (2002)
- Max Delbrück Medal, Max Delbrück Centrum für Molekulare Medizin, Berlin (2002)
- Wolf Prize in Medicine, Israel (2004)
- Keio Medical Science Prize, Japan (2004)
- UCSD Chancellor's Associates Award for Excellence in Science & Engineering Research, UC San Diego (2004)
- Perl Prize in Neuroscience, University of North Carolina (2004)
- Associate Member, European Molecular Biology Organization (2005)
- J.Allyn Taylor International Prize in Medicine, Robarts Research Institute, Canada (2005)
- ABRF Award, Association of Biomolecular Resource Facilities (2006)
- Lewis S. Rosenstiel Award for Distinguished Work in the Basic Medical Sciences, Brandeis University (2006)
- Foreign Member of the Royal Society, UK (2006)
- BioPharma Leadership Award, the 6th Annual San Diego BioPharma Conference, San Diego (2007)
- US Department of Defense (DoD) Breast Cancer Innovator Award
- Nobel Prize in Chemistry, Sweden (2008)
- E.B. Wilson Medal, American Society for Cell Biology (2008)
- Honorary Fellow of the Royal Society of Chemistry (HonFRSC), UK (2008)
- Honorary Academician, Academia Sinica (2008)
- February 18, 2009, Roger Tsien Day, in the City of San Diego, California, USA
- Distinguished Science and Technology Award, The 2009 Asian American Engineers of the Year (AAEoY) Award (April 2009)
- Lifetime Innovation Award, UC San Diego (May 20, 2009)
- AHA Distinguished Scientists, American Heart Association (2009)
- Molecular Imaging Achievement Award, Society of Molecular Imaging (2009)
- Doctor of Science honoris causa, The University of Hong Kong (2009)
- Doctor of Science honoris causa, Chinese University of Hong Kong (2009)
- General President Gold Medal, the 97th Indian Science Congress, India (January 3, 2010)
- Spiers Memorial Award, Royal Society of Chemistry, UK (2010)
- Bowditch Lectureship, American Physiological Society (1992)
- Hans L. Falk Memorial Lectureship, National Institute of Environmental Health Sciences (1993)
- Quastel Lectureship, Hebrew University of Jerusalem (1994)
- President's Lectureship, American Thoracic Society (1994)
- Roger Eckert Memorial Lecture, Göttingen Neurobiology Conference of the German Neuroscience Society (1995)
- Melvin Calvin Lectureship, UC Berkeley (1999)
- Herbert Sober Lectureship, American Society for Biochemistry and Molecular Biology (2000)
- Keith Porter Lectureship, American Society for Cell Biology (2003)
- Konrad Bloch Lectureship, Harvard University (2003)
- Grass Foundation Lectureship, Society for Neuroscience (2004)
- The 1st Academia Sinica Lecturer (the highest honor of the academy), Dec 2009
- The 2010 National Lecturer of the Biophysical Society (the highest honor of the society)
- The 2011 UCL Prize Lecture in Clinical Science (University College, London)
- 诺贝尔化学奖得主钱永健系吴越国王34世孙 [Nobel Chemistry Prize winner Roger Tsien is the 34th-generational descendant of the King of Wuyue] (in Chinese). Sina.com. October 9, 2008. Retrieved October 9, 2008.
- Ruth Williams; Horsfall, MJ; Van Helten, JB; Glickman, BW; Mohn, GR (October 8, 2007). "People & Ideas – Roger Tsien: Bringing color to cell biology". J Cell Biol 179 (1): 6–8. doi:10.1083/jcb.1791pi. PMC 2064723. PMID 17923526.
- Steele, D. (2004) Cells aglow. HHMI Bulletin, Summer 2004, 22–26
- Nicole Kresge, Robert D. Simoni, and Robert L. Hill. "The Chemistry of Fluorescent Indicators: the Work of Roger Y. Tsien", Journal of Biological Chemistry, September 15, 2006. Accessed September 18, 2007. "At age 16, Tsien won first prize in the nationwide Westinghouse talent search with a project investigating how metals bind to thiocyanate."
- Swayze, Bill. "Jersey teens call science a winner: Two finalists say just being in Westinghouse talent competition is prize enough", The Star-Ledger, March 11, 1997. Accessed September 18, 2007. "Only one New Jersey teenager has ever captured top honors in the history of the competition. That was Roger Tsien in 1968. The then-16-year-old Livingston High School math-science whiz explored the way subatomic particles act as bridges between two dissimilar metal atoms in various complex molecules."
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- Nobel lecture
- Shaner N, Steinbach P, Tsien R (2005). "A guide to choosing fluorescent proteins" (PDF). Nat Methods 2 (12): 905–9. doi:10.1038/nmeth819. PMID 16299475.
- Heim R, Cubitt A, Tsien R (1995). "Improved green fluorescence" (PDF). Nature 373 (6516): 663–4. doi:10.1038/373663b0. PMID 7854443.
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- Xiaokun Shu, Antoine Royant, Michael Z. Lin, Todd A. Aguilera, Varda Lev-Ram, Paul A. Steinbach, Roger Y. Tsien (2009). "Mammalian Expression of Infrared Fluorescent Proteins Engineered from a Bacterial Phytochrome". Science 324 (5928): 804–07. doi:10.1126/science.1168683. PMC 2763207. PMID 19423828.
- Miyawaki A, Llopis J, Heim R, McCaffery JM, Adams JA, Ikurak M, Tsien RY (1997). "Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin.". Nature 388 (6645): 882–7. doi:10.1038/42264. PMID 9278050.
- B. Albert Griffin, Stephen R. Adams, Roger Y. Tsien (1998). "Specific Covalent Labeling of Recombinant Protein Molecules Inside Live Cells". Science 281 (5374): 269–72. doi:10.1126/science.281.5374.269. PMID 9657724.
- "PNAS: Fluorescence + MR imaging probe can guide cancer surgery" (php). PNAS. March 4, 2010. Retrieved March 11, 2010.
- San Diego Science Festival Lunch with a Laureate
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