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 nationwideWestinghouse Talent Search with a project investigating how metals bind tothiocyanate.[12]
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 ofcalcium ions and other ions important in biological processes.
GFP Movie showing entire structure and zoom in to fluorescent chromophore. Movie created by Erik A. Rodriguez with UCSFChimera fromPDB: 1EMA in memory of Roger Y. Tsien forBirch Aquarium.
In 2004, Tsien was awarded theWolf 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."[21]
In 2008, Tsien shared the Nobel Prize in Chemistry withOsamu Shimomura andMartin Chalfie for "the green fluorescent protein: discovery, expression and development."[8][22]
The multicoloredfluorescent 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 a suitable wavelength of 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.[9]
Since the discovery of thewild typeGFP, numerous different mutants of GFP have been engineered and tested.[23] The first significant leap forward was asingle point mutation (S65T) reported by Tsien in 1995 inNature.[24] This mutation dramatically improved the fluorescent (bothintensity andphotostability) 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 availableFITC 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 of Roger Y. Tsien include Atsushi Miyawaki andAlice Y. Ting.
Timelines of GFP-development involved by Tsien:[22]
1994: Tsien showed the mechanism that GFPchromophore is formed in a chemical reaction which requiresoxygen 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".
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 (byin vitro andin vivo directed evolutions).
In 2009, a new kind of Infrared Fluorescent Protein (IFP) was developed by Tsien's group, and further reported and described byScience. The new IFPs are developed frombacterialphytochromes instead of frommulticellular organism likejellyfish. 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 bygenetic means such assite-directed mutagenesis. In order to fluoresce, IFPs require an exogenouschromophore,biliverdin.[26]
Roger Tsien built the foundation of next generation sequencing technology that became widely used. On 26 October 1990,Roger Tsienet al. filed a patent of stepwise ("base-by-base") sequencing with removable 3' blockers on DNA arrays. Illumina integrated this concept with DNA cloning for their next generation sequencer.[29]
Tsien was a pioneer ofcalcium imaging and known for developing various dyes which become fluorescent in the presence of particular ions such as calcium.[9][11] One such dye,fura-2, is widely used to track changes of calcium concentration within cells.indo-1 andfluo-3, other popular calcium indicators, were also developed by Tsien's group in 1985 and 1989 respectively. He has also developed fluorescent indicators for other ions such as magnesium, zinc, copper, iron, lead, cadmium, aluminum, nickel, cobalt, and mercury.[30]
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 thecalmodulin-based sensor, namedCameleon.[31]
FlAsH-EDT2 is a biochemical method for specific covalent labeling of proteins harboring a tetracysteine motif (CCXXCC). It's a method based on recombinant protein molecules, and was developed by Tsien and his colleagues in 1998.[32]
Mouse experiments by Tsien's group suggest that cancer surgery can be guided and assisted by fluorescentpeptides. 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.[33]
Tsien was also a notable biochemical inventor and held or coheld about 100 patents till 2010. In 1996, Tsien cofounded the Aurora Biosciences Corporation, which went public in 1997. In 2001, Aurora was acquired by theVertex Pharmaceuticals. Similarly, Tsien was also a scientific cofounder ofSenomyx in 1999.[12][34]
Tsien also promoted science education to promising young scientists through the first-ever San Diego Science Festival Lunch with a Laureate Program.[35]
Tsien is a 34th-generationaldescendant of the King ofWuyüeh,Tsien Liu.[36] Tsien's parents Hsue-Chu Tsien and Yi-Ying Li (李懿穎) came fromHangzhou and Beijing, respectively.
Tsien was the younger brother ofRichard Tsien, a neurobiologist atNew York University,[38] and Louis Tsien, a software engineer. Tsien, who called his own work molecular engineering, once said, "I'm doomed by heredity to do this kind of work."[39]
Tsien died on August 24, 2016.[40] Although the specific cause of death was not disclosed, it was reported that he died while on a bike trail inEugene, Oregon.[41] Prior to his death, Tsien had survivedcancer and suffered astroke in 2013.[42][43]
"He was ahead of us all," said Tsien's wife, Wendy. "He was ever the adventurer, the pathfinder, the free and soaring spirit. Courage, determination, creativity and resourcefulness were hallmarks of his character. He accomplished much. He will not be forgotten."[15]
^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. RetrievedOctober 9, 2008.
