Roger Y. Tsien

Roger Tsien
Born	Roger Yonchien Tsien (1952-02-01) February 1, 1952 New York City, United States
Residence	San Diego
Citizenship	United States
Nationality	American
Fields	Biochemistry
Institutions	University of California, San Diego University of California, Berkeley
Alma mater	Harvard University University of Cambridge
Thesis	The design and use of organic chemical tools in cellular physiology (1976)
Doctoral advisor	Jeremy Sanders
Known for	Green fluorescent protein Calcium imaging
Notable awards	Nobel Prize in Chemistry (2008) Golden Goose Award (2012) E. B. Wilson Medal (2008) Rosenstiel Award (2006) ForMemRS (2006) Wolf Prize in Medicine (2004) Keio Medical Science Prize (2004) Dr A.H. Heineken Prize (2002) Artois-Baillet Latour Health Prize (1995) Gairdner Foundation International Award (1995)
Website www.tsienlab.ucsd.edu

Roger Y. Tsien
Traditional Chinese	錢永健
Simplified Chinese	钱永健
Transcriptions Standard Mandarin Hanyu Pinyin Qián Yǒngjiàn

Roger Yonchien Tsien (Chinese: 錢永健) (born February 1, 1952) is an American biochemist. He is a professor at the Department of Chemistry and Biochemistry, University of California, San Diegoand 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.

Education and early life

Tsien was born in New York, in 1952. He grew up in Livingston, New Jersey and attended Livingston High School there.

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, Cambridge 1977 for research on The Design and Use of Organic Chemical Tools in Cellular Physiology supervised by Jeremy Sanders.

Research and career

Following his PhD, Tsien was a Research Fellow at Gonville and Caius College, 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 contributed to 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."

In 2008, Tsien shared the Nobel Prize in Chemistry with Osamu Shimomura and Martin Chalfie for "the green fluorescent protein: discovery, expression and development."

Fluorescent proteins

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.

Since the discovery of the wild type GFP, numerous different mutants of GFP have been engineered and tested. The first significant leap forward was a single point mutation (S65T) reported by Tsien in 1995 in Nature. This mutation dramatically improved the fluorescent (both intensity and photostability) and spectral characteristics of GFP. A shift of the major excitation peak to 488 nm with the emission peak staying at 509 nm thus can be clearly observed, which matched very well the spectral characteristics of commonly available FITC facilities. All these then largely amplified the practicality of using GFP by scientists in their research. Tsien mainly contributed to much of our understanding of how GFP works and for developing new techniques and mutants of GFP.

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 Infrared Fluorescent Protein (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 fluoresce, tetrapyrrole is also required, however, it's abundant in living bodies.

Calcium imaging

Tsien is a pioneer of calcium imaging and 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

FlAsH-EDT2 is a biochemical method for specific covalent labeling inside live cells. It's a method based on recombinant protein molecules, and was developed by Tsien and his colleagues in 1998.

• "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 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 went public in 1997. In 2001, Aurora was acquired by the Vertex Pharmaceuticals. Similarly, Tsien was also a scientific co-founder of Senomyx in 1999.

Dr. Tsien also helps promote science education to promising young scientists through the first-ever San Diego Science Festival Lunch with a Laureate Program.

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-UNC Neuroscience Prize, 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)
• Elected a Foreign Member of the Royal Society (ForMemRS) in 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)
• Golden Goose Award (2012)

Named lectures and lectureships

• 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 Lecture, 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)

Personal life

According to the Qian (Tsien) clan genealogy book, Tsien is a 34th-generational descendant of King Qian Liu of the Wuyue Kingdom of ancient China.

Tsien has a number of 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."