Over the three decades of their careers in the Structural Studies Division at the LMB Chris and Kiyoshi determined several crystal NMR structures of components of the spliceosome and more recently elucidated high-resolution structures of the whole spliceosome at different catalytic stages using electron cryo-microscopy (cryo-EM). Kiyoshi Nagai was Group Leader and Joint Head of Structural Studies from 2001 to 2010. He died on September 27th 2019 after a short illness. Chris Oubridge was a senior scientist in Kiyoshi’s group for over 30 years. He died on Tuesday 25th August 2020.
The Symposium was opened by Jan Löwe, LMB Director. He reflected on what Chris and Kiyoshi had taught him. “Big important problems are the goals” and “Highly successful scientists do not have to be showy.” Commenting on the dedication both scientists demonstrated during their 30-year quest to understand the spliceosome, he also added “Never give up – if the problem is worth it keep going”.
The programme included talks by many of Kiyoshi and Chris’s former colleagues and scientists influenced by their work and family members. LMB emeritus and former supervisor of Kiyoshi, John Kilmartin, commented that “Kiyoshi really flourished, he got things done, and he was absolutely astonishing.” Kelly Nguyen, a former PhD student of Kiyoshi, recollected that Kiyoshi had told her that “It’s never too late to try and learn something new”. She also added “Take pride as well as responsibility of your science.”
Kelly later closed the event with a video from Chris Oubridge speaking about Kiyoshi. He spoke highly of Kiyoshi and had commented that Kiyoshi liked people who would be ambitious and throw themselves at projects.
Chris and Kiyoshi’s collaboration started around the 1990’s. The focus of their research was structural analysis of the spliceosome, a complicated and formidable multi-subunit molecular machine that removes introns from transcribed pre-mRNA. They made an early breakthrough by determining the crystal structure of the RNA-binding domain of the U1 snRNP A protein, a key component of U1 snRNP, one of the major components of the spliceosome. In the Nagai group’s last LMB Insight on Research article, published in April 2019, their latest cryo-EM structure was highlighted, which revealed the previously unknown mechanism by which the splice site at the start of an intron is brought to the active site of the human spliceosome, allowing the reaction to begin. Over the years, the spliceosome structures determined by the Nagai group contributed enormously to our current understanding of the fundamental cellular process of pre-mRNA splicing.
Kiyoshi Nagai (1949 – 2019)
Chris Oubridge (1966 – 2020)
Royal Society Biographical Memoir of Kiyoshi Nagai, Andy Newman and Ben Luisi, 2022