Text | Yang Yungui (Researcher, Beijing Institute of Genomics, Chinese Academy of Sciences)
On the afternoon of October 7, Beijing time, the Royal Swedish Academy of Sciences announced the winners of the 2015 Nobel Prize in Chemistry, and Thomas Lindahl from Sweden, Paul Modrich from the United States and Aziz Sancar from Turkey jointly won this honor in recognition of their contributions to the study of the mechanism of DNA repair. The theory of DNA repair mechanisms they discovered extended to cancer treatment very early on, providing theoretical guidance for chemoradiation and chemotherapy.
I was thrilled to hear that Thomas Lindal had won the Nobel Prize, because the winner was my mentor for three years. At this moment, the past is coming like a tide. In 2000, after graduating from the Shanghai Branch of the Chinese Academy of Sciences, I came to Lyon, France, on the recommendation of my supervisor, Professor Yang Shengli, an academician of the Chinese Academy of Engineering, to carry out postdoctoral work at the "International Cancer Research Agency" set up by the World Health Organization (WHO), under the supervision of Professor Wang Zhaoqi, an academician of the European Academy of Sciences. It was there that I first came into contact with the model animal mice commonly used in basic tumor research and learned for the first time about the concept of DNA damage repair.
Speaking of DNA damage repair, we have to mention Thomas Lindal, who is known as the "father of DNA damage repair". Since the discovery of the DNA double helix structure, it was once thought that DNA is a fixed and unchanging structure. But in the 1970s and 1980s, Thomas discovered that DNA was not as stable as people thought, and damage could occur under the influence of ultraviolet rays, free radicals and other external conditions. Thomas's contribution is to be the first to observe the degradation and damage of DNA, breaking the scientific community's long-held belief that the structure of the DNA double helix is extremely stable, and on this basis, innovatively discovered the mechanism of DNA repair.
For these reasons, I had the idea of going to Professor Thomas Lindal's lab to continue my studies. At that time, he was a member of the Royal Academy of Sciences. On the recommendation of Academician Wang Zhaoqi, in September 2005, I was given the valuable opportunity to go to Thomas's laboratory for an interview. On the flight to London, my mind was constantly imagining what the clare hall laboratories, known as "one of the holy places of DNA restoration," would look like. What kind of scientist is Thomas? It wasn't until the driver took me from the airport to the lab that I was surprised to find that Clare's lab was located on the outskirts of London surrounded by countryside, and the silence was incomparable. The next day when I met Thomas for the first time in the lab, he impressed me. He enthusiastically arranged for me to communicate with the members of the research group and many professors, took me on a tour of the laboratory, and made me feel a first-class academic atmosphere of pursuing innovation and cooperation, and my desire to join the Thomas team was even stronger. I remember that night Thomas invited me to a restaurant and ordered mussels (also called sea red). After returning to France, I received an email from Thomas, who warmly welcomed me as his last postdoc, what we Chinese commonly call "closed disciple."
Clare's laboratory surrounded by idyllic gardens
But when it comes to making the decision to move from Lyon, France, where welfare benefits are good and the climate is superior, to London, where it's cheaper, rains and more expensive, it's challenging for a family with two-year-olds. My wife Xuanchen and my relatives in China gave me great courage and support at this time, and made me make up my mind to go to London. In November 2005, I officially became a student of Thomas. At that time, Thomas was 68 years old and was about to retire from the post of director of the institute. Thomas, who was second-tiered, spent most of his time in the lab, and that's when my real understanding of him began.
During this period with the mentor, we discussed the most in addition to science or science, which made me feel the old scientist's dedication to the science he loved and the spirit of tireless and diligent pursuit, as well as his excitement after discovering the phenomenon of DNA damage and repair mechanisms. His colleague Tim Hunt (winner of the 2001 Nobel Prize in Physiology or Medicine) commented that his love and passion for science was never-ending. I strongly agree with that.
In the eyes of outsiders, Thomas is a very rigorous scientist, but in fact he is also a witty and humorous gentleman without any old-fashionedness. He often joked with his students. I remember that I used to have lunch with him in the unit cafeteria, and on a few occasions when Thomas and I bought the same steak, the chef tended to give me a smaller steak, and the steak for Thomas was generally larger. Thomas humorously explained that it might be that the chef thought his tall man needed more energy, while my little one needed to consume a little less energy.
In terms of scientific research, Thomas is very strict with me. But in life, he always cared about me. He knew that I worked hard in England with my family of three, and although I never complained to him about the high prices, he made an exception and gave me a raise and told me to keep this little secret.
Thomas is a veritable academic mentor, often arranging for students to participate in important academic exchange activities, focusing on cultivating students' original scientific thinking and keen ability to grasp new things, which has a profound impact on students' scientific research careers, and most of his disciples have become accomplished scientists. Because many of the topics in his research team are original and there are no ready-made answers and clues, he often encounters confusion and problems when doing scientific research, and sometimes feels frustrated. Thomas would encourage us: "If you go through all the scientific literature on a problem and don't find a solution that works today, then on the basis of your own deep thinking and full communication with other experts in the field, a good scientific problem may be formed, and this is where you are worth trying—if the problem is easy to solve, others have already solved it, and you don't need to solve it." ”
And when students achieve achievements, he will tell us: "Any achievement, to inherit the development, do not always look back, think more about the next step!" "Thomas is a rigorous person, not only in his rigorousness of scientific experiments and scientific data, but also in his more rigorous examination of his authority and abilities. He often said to us: "When discussing problems, you must not fully believe what I say, but must seek verification - after all, I am older, and my ability to receive new things has declined." ”
On 30 November 2007 in London, Thomas and Beverly attended the 110th Anniversary Royal Society Annual Meeting.
Thomas was also a brilliant scientific administrator. He led The Clare Laboratory, which enrolled fewer than 20 independent researchers, became the top laboratory in the field of nucleic acid biology research in 25 years, producing more than 10 members of the Royal Academy of Sciences and two Nobel laureates (Tim and Thomas). Commenting on Thomas's achievements, Tim concluded that Thomas's scientific achievements, in addition to his own outstanding scientific discoveries in dna repair mechanisms, should also include the outstanding achievements of outstanding students and colleagues under his leadership and guidance, which are also part of Thomas's success.
In November 2008, I will end my postdoctoral career in Thomas's laboratory, and when Faced with future choices, Thomas told me: "The future development of life sciences depends on genomics, and it is recommended that you combine new methods of molecular and genomics; and China's economy is developing rapidly, you can make a difference."
His suggestion coincides with the advice of our domestic mentor Academician Yang Shengli. Therefore, I decided to return to China for development, and I was fortunate to be selected into the "Hundred Talents Program" of the Chinese Academy of Sciences and came to the Beijing Genomics Research Institute to establish my own laboratory. Before returning home, Thomas and his wife Beverly graciously invited our family of three to visit his house, personally cooked delicious herbs and grilled multi-treasure fish for us, and gave me the experimental materials for his research direction, hoping that I could make more and better original research.
As his "closed disciple", I decided to take another step on the basis of continuing Thomas's DNA repair research and began to study the reversibility of RNA modifications in the intermediate vectors of genetic material DNA releasing genetic information. With thomas's support, the main chemical modification of RNA was discovered by collaborating with Professor He Chuan of the University of Chicago to modify the enzyme RNA mainly by methylated m6a (6-methyladenine), demonstrating the reversibility of RNA chemical modification and its important function of regulating RNA processing and metabolism. From the establishment of the laboratory to the advice of some scientific research directions and details today, Thomas has always stood behind me and supported me.
On November 20, 2008 in London, Thomas and Beverly invited my family to visit.
After retirement, although Thomas is no longer engaged in front-line scientific research, he often provides guidance, consultation and evaluation opinions for internationally renowned scientific research institutions. After returning to China, I invited Thomas to visit China three times for academic exchanges and guidance, and in 2009 he became a member of the editorial board of genomics, proteomics & bioinformatics (GPB), an academic journal of the Genomics Institute, in 2010, he was awarded the Overseas Distinguished Fellow of the Chinese Academy of Sciences; in 2013, his academic achievement review was published in GPB under the title "My Journey to Dna Repair". In 2014, when Thomas came to China to participate in the "Fourth International Symposium on DNA Damage Response and Human Diseases", he spoke highly of the progress made by Chinese scholars in this field. In June of this year, my brother-in-law Professor Arne Klungland and I successfully organized the "Tomas Lindahl Conference on DNA Repair" in Norway.
Thomas and my research team in Beijing on October 21, 2009
On June 20, 2015, Thomas, Anne and I were in Oslo, Norway
Looking back on that year, I am very grateful to the three supervisors in my doctoral and postdoctoral research careers, namely Yang Shengli, Wang Zhaoqi and Thomas Lindal. They are beacons of my career, illuminating the unknown scientific road ahead of me.
Finally, I conclude by quoting a passage from Thomas that confirms that the Nobel laureate Thomas is actually an old boy in science: "i still enjoy very much doing science. it is pleasure, it is very interesting and it is stimulating. it changes all the time. i would like to be here around hundred years to see how science develops.-my journey to dna repair。 (I still thoroughly enjoy doing scientific research.) It's very enjoyable, fun and exciting work. It moves forward in constant change. I am willing to continue to work for science for hundreds of years and witness its continuous development. )”
I believe that the wishes of the elderly will be fulfilled.
(This article was published on the website of the Beijing Institute of Genomics of the Chinese Academy of Sciences on October 9, with the original title "My Teacher-Student Relationship with Nobel Laureate Thomas Lindahl", and the author authorized "Intellectual" to reprint exclusively and slightly revised.) ）