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.
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.
GFP Movie showing entire structure and zoom in to fluorescent chromophore. Movie created by Erik A. Rodriguez with UCSF Chimera from PDB: 1EMA in memory of Roger Y. Tsien for the Birch Aquarium.
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.
Since the discovery of the wild typeGFP, 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 of Roger Y. Tsien 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".
Roger Tsien had built the foundation of next generation sequencing technology that is widely used today. 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.
Tsien was 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 ions such as magnesium, zinc, copper, iron, lead, cadmium, aluminum, nickel, cobalt, and mercury.
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 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.
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.
Tsien was 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.
Tsien also promoted science education to promising young scientists through the first-ever San Diego Science Festival Lunch with a Laureate Program.
Tsien was the younger brother of Richard Tsien, a renowned neurobiologist currently at New York University, 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."
On August 31, 2016, a press release by UC San Diego announced the death of Prof. Tsien. He died on August 24, 2016. Although the actual cause of death is yet to be determined, he seemed to have died while on a bike trail in Eugene, Oregon. Prior to his death, Tsien had survived cancer and suffered a stroke in 2013.
"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."
Awards and honors
Roger Y. Tsien has received numerous honors and awards in his life, including:
National 1st Prize, Westinghouse Science Talent Search (1968)
^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. PMID9278050.