Profile of Yigong Shi

Growing up in rural China under the imposed hardships of the cultural revolution, Yigong Shi did not have the luxury of toys. Instead Shi, now the dean of the School of Life Sciences at Tsinghua University in Beijing, made elaborate models out of clay he collected from the fields. “I would stay for hours to a make a ship or train model with small parts,” he recalls. Decades later, as a structural biologist, Shi is still making models, albeit with different tools. Elected to the National Academy of Sciences in 2013, Shi studies the molecular mechanisms that govern the awakening of apoptotic enzymes in worms, fruit flies, and mammals, seeking to illuminate function by revealing structure. Yigong Shi. Image courtesy of Tsinghua University. Macromolecular machine for cell death. Shown here is a 3D structure of the CED-4 apoptosome, formed by eight molecules of the CED-4 protein. Each CED-4 molecule contains five domains: caspase recruitment domain (green), nucleotide-binding domain (blue), helical domain I (cyan), winged-helix domain (magenta), and helical domain II (red). Apoptosis, or programmed cell death, is a process akin to cellular containment and cleaning. An evolutionarily conserved cascade of enzyme activity triggers this tightly orchestrated cellular dismantling, which is especially important during embryonic development and tumor formation. In his Inaugural Article (1), Shi examines the fundamental mechanism of the final enzyme in the cascade, offering what he calls “a somewhat controversial conclusion” regarding caspase activation. He demonstrated that the enzyme caspase-9, which controls cell death triggered by intracellular stress signals, is awakened in a complex process that requires the cooperation of another protein, Apaf-1. Born in 1967, Shi spent most of his early childhood in rural China. His parents were relocated to Zhumadian in 1969 as part of a government effort during the cultural revolution. The family experienced hardship, …