Chikashi Toyoshima (豊島 近, Toyoshima Chikashi, born July 17, 1954) is a Japanese biophysicist.^[1] His research focuses on two proteins: the Ca²⁺-ATPase of muscle sarcoplasmic reticulum, and the Na⁺, K⁺-ATPase expressed in all animal cells.^[2] He is a professor at the University of Tokyo and the Foreign Associate of the National Academy of Sciences, USA.^[3] Toyoshima's research about the Ca²⁺-ATPase started in 1989. In the next few years, he and his colleagues obtained the world's first series of images of Ca²⁺-ATPase at the atomic level.^[4] Via x-ray crystallography, cryo-EM and other methods, he has determined the crystal structures of ten intermediates of Ca²⁺-ATPase. On September 10, 2015, The Royal Swedish Academy of Sciences awarded him and Poul Nissen the Gregori Aminoff Prize of 2016 for their fundamental contributions to understanding the structural basis for ATP-driven translocation of ions across membranes.^[5]

Early life and education

Toyoshima was born in the small town of Honjo in the prefecture of Akita, Japan. The elementary school in Honjo focuses on developing children's ability in science, writing, sports, and the arts. Toyoshima and his older brother worked on science experiments with their mother, a high school home economics teacher^[6] and were successful in science research contests throughout Akita. Toyoshima also showed an early talent for creative innovation. He spent his free time constructing models of planes and ships out of plastic and wood. When he was older, he developed an interest in toy electronics.^[4] He later recalled that the experiences he had with science during his youth helped him when he entered a highly technical field. Initially, Toyoshima wished to become a doctor. However, since his older brother had studied medicine in college, he thought it was unnecessary to have two medical doctors in the family. So, he decided to choose another branch of science despite his high school teacher's suggestion that he study literature and writing in college. He finally decided on physics, which was a popular choice at the time and easier for him than literature.
In 1973, he was admitted by the University of Tokyo on his first trial. He contemplated his possibility of surviving academically in so rigorous an environment. In his first two years, he studied standard physics but also took classes in the biochemistry and botany departments. In the middle of his third year, he visited Setsuro Ebashi's laboratory, which worked with electron microscopes. He decided to carry out a small project in Ebashi's laboratory, where he continued to research the microscopy of muscle thin filaments and myosin heads for his master's and doctoral research after he received his undergraduate degree in 1978. He completed his PhD in 1983.^[1][4]

Career

In 1984, Toyoshima became a research associate at the University of Tokyo after he got his doctorate. Two years later, he took a postdoctoral position at the laboratory of biophysicist Nigel Unwin at Stanford University. Under Unwin, Toyoshima worked to develop mathematical methods for disentangling the superimposed information from a projection image, or electron micrograph, of a tubular structure. In 1988, he followed Unwin to the Medical Research Council's Laboratory of Molecular Biology, where he met fellow biophysicist David Stokes, who was studying Ca²⁺-ATPase. He also worked with Stokes. After moving back to Japan in 1989, he joined the Frontier Research Program at RIKEN as a research scientist. He moved to the Tokyo Institute of Technology as an associate professor in 1990. In 1994, Toyoshima was offered a faculty position at University of Tokyo, where he is currently a professor at the Center for Structural Biology of Challenging Proteins within the Institute of Molecular and Cellular Biosciences.^[1][2][4]

Research

Early in his research career, Toyoshima worked on "3D image analysis of muscle thin filaments decorated by myosin heads" as an electron microscopist in the Department of Physics at the University of Tokyo.^[7] He then turned to acetylcholine receptor research after he went to Unwin's laboratory to study cryogenic electron microscopy (cryo-EM) in 1986. By developing a new mathematical algorithm to untangle the superimposed images obtained from the cryo-EM, he managed to reconstruct the 3D structure of an ion channel at 17 Å resolution.^[8] This was the first 3D structure of the ion channel. It was met with great excitement among academics.^[2] Soon afterwards, the same method was applied to reconstruct the 3D structure of Ca²⁺-ATPase with help from David Stokes. Toyoshima and Stokes published their analysis of the structure of this protein in Nature in 1993.^[9] After returning to Japan, Toyoshima's later research continued to focus on the structure of Ca²⁺-ATPase. Through combining the x-ray crystallography and the crystallization methods for electron microscopy, Toyoshima obtained and photographed large crystals of Ca²⁺-ATPase in their first state, the E1·2Ca²⁺. He published his research—the first high-resolution images of P-type ATPases—in 2000.^[10] Over the following years, he published a series of crystal structures of Ca²⁺-ATPase. As of 2023, he has determined the crystal structures of this ATPase in ten different states by x-ray crystallography, covering roughly the entire reaction cycle. He also extended his research to Na⁺, K⁺-ATPase^[11] and has developed a methodology for electron crystallography of ultrathin 3D protein crystals.^[12]

Awards

• Asahi Prize, Asahi Shimbun (2009)^[13]
• Yamazaki-Teiichi Prize (2011)^[14]
• Medal with Purple Ribbon (2015)^[15]
• Uehara Prize，The Uehara Memorial Foundation (2015)^[1]
• Gregori Aminoff Prize, The Royal Swedish Academy of Sciences (2016)^[5]

References

External links

• Toyoshima Lab
• research map of Prof Toyoshima