"Soil Postdoc" Liu Zhen: Creating "Made in China" in the field of somatic cell cloning

"My parents wanted me to be serious, and that's what the word 'true' in my name means." Liu Zhen, 33, was born into a rural family in Weifang, Shandong Province. After graduating from Shandong Normal University with a major in biotechnology 11 years ago, he was admitted to the Center for Excellence in Brain Science and Intelligent Technology (Institute of Neuroscience) of the Chinese Academy of Sciences, where he studied under Sun Qiang, director of the non-human primate research platform, "never imagining that the decision to study for graduate school would open up a long road of exploration in the field of non-human primate genetic modification model construction and technology research and development." Liu Zhen said.

As the youngest research group leader of the Institute of Neuroscience at that time, Liu Zhen, a "soil postdoc", proved that young scientists in China have the ability to achieve independent control of key technologies - in 2016, as the first author, he published a research paper on the MECP2 transgenic monkey model of MECP2 autism in Nature, and was awarded the annual "Top Ten Advances in Chinese Science" and "Top Ten Advances in Chinese Life Sciences"; in 2018, he and his team successfully bred the world's first somatic cell cloning monkeys. Created "Made in China" in the field of somatic cell cloning.

Recently, Liu Zhen won the 25th "Chinese Youth May Fourth Medal", which he believes is not only an affirmation of his scientific research achievements, but also an encouragement to all local young scientists.

Rooted in a small island, hard practice somatic cell nuclear transplantation technology

Liu Zhen's dream began with a monkey farm laboratory on Xishan Island in the center of Taihu Lake in Suzhou, Jiangsu Province, where the non-human primate research platform was built in 2009.

"Everyone rented a house in the town, took turns to cook, and the transportation to and from the laboratory was a few battery cars. There are no street lights on the path, and once Teacher Sun broke a broken bone while riding a bicycle. In 2010, Liu Zhen followed Sun Qiang to Xishan Island and stayed for 10 years. That time strengthened his determination to pursue lifelong research on non-human primates.

For the research and development of drugs for brain diseases, in the past, with the help of mouse models that are far from humans, most of the drugs developed are ineffective or have side effects in human testing, which is one of the reasons why special drugs for curing autism, intellectual disability, schizophrenia, depression, Alzheimer's disease and other diseases have not been developed.

"Non-human primates, dominated by cynobial monkeys and rhesus monkeys, have physiological anatomical structures and genetic information that are more closely related to humans, and are ideal model animals for brain disease and advanced brain cognitive research." In 2009, the Center for Excellence in Brain Science and Intelligent Technology (Institute of Neuroscience) of the Chinese Academy of Sciences established a non-human primate research platform to "attack" this internationally recognized problem.

After coming to the island, one of Liu Zhen's main tasks was to practice embryo microscopy. Because the nuclear transplantation micromanage of monkeys and other primates is more technically demanding than that of experimental animals such as mice, Liu Zhen sits in front of the microscope for more than 6 hours almost every day, repeating the somatic cell "denuclearization" operation over and over again, a little bit of technical details: using a glass needle only 10 microns thick, through the macaque egg cells with a diameter of only more than 100 microns, find the looming nuclei in the line of sight, and gently remove them.

After day-to-day practice, Liu Zhen can complete an oocyte "denuclearization" operation in 10 seconds.

Abandon the foreign independent customization into the talent road

"MECP2 is an autism-related gene, and overexpression of this gene can lead to the occurrence of autism." During his PhD studies, Liu Zhen ushered in the first topic - the use of lentiviral transgenic methods to construct MECP2 overexpression transgenic monkeys. In 2016, Liu Zhen and his team members found that the autism phenotype similar to humans in the first generation of transgenic monkeys was also passed on to the next generation, providing a more advanced animal model for the study of the pathogenesis mechanism and intervention methods of autism.

"In most cases, scientific research itself is not exciting, nor will there be any 'genius ideas', but more step by step and solid research." Liu Zhen admitted that he likes to stay in the laboratory the most, "One year during the Spring Festival, the veterinary staff could not be deployed, so I chose to stay on the island to help feed the monkeys and continue to study the problems." ”

After graduating with a doctorate in 2017, Liu Zhen faced the choice of staying. If he follows a shortcut to "becoming a talent" in the field of domestic life science research in the past, he can go to a top foreign research institution to do postdoctoral work, and then return to China to apply for a talent program to obtain the support of research funds and preferential policies for settling down.

"At that time, the institute was challenging the problem that had plagued the field for 20 years, the somatic cloning monkey, and if I went abroad, I would probably not be able to participate in it." Liu Zhen told reporters that due to the relatively small number of non-human primate research, high input costs and long output cycles, most people are not optimistic about somatic cell cloning monkey research, "but whether it is funding support or the construction of research platforms, the Institute of Neuroscience is more suitable than any foreign institution abroad." ”

After thinking about it, Liu Zhen customized his own path to becoming a talent: abandoning staying in the West and staying in China to carry out postdoctoral research. Soon, he received a funding of 600,000 yuan from the "Postdoctoral Innovative Talent Support Program", which once again strengthened his determination to stay.

Break the mold and hire "soil postdocs" to create independent IP

"The birth of 'Middle-Middle' proves that my choice is correct." On November 27, 2017, the 18th anniversary of the establishment of the Institute of Neuroscience, the Liu Zhenhe Institute received a precious gift: the successful cultivation of the world's first somatic cell cloning monkey "Zhongzhong". On December 5 of the same year, the second individual cell cloning monkey "Huahua" was born, marking the first time in China to open a new era of somatic cloned monkeys as experimental animal models, and China became the "leader" in the field of cloning.

Liu Zhen and his team members first grow the somatic cells of the macaque in vitro, remove the nucleus, and then inject it into the oocyte of another macaque monkey that has been removed from the nucleus. This cloned embryo was then transferred to the macaque monkey's uterus, and the resulting macaque monkey was the somatic clone monkey "Zhongzhong" and "Huahua". This seemingly easy operation is a problem that scientists around the world have been unable to overcome in the past 20 years. In this regard, Emilie Marcus, editor-in-chief of the journal Cell, also praised the work of somatic cell cloning monkeys as "a milestone in the field of biotechnology in the field of nearly 20 years".

"Grasp every slim opportunity, grasp every subtle knowledge, do your best to do the best, and everything will come to fruition." Liu Zhen believes that the success of somatic cell cloning monkeys has made sun Wukong's picture of "plucking hair and becoming monkeys" come true, "This breakthrough has further consolidated the dominance of Chinese scientists in the 'whole brain mesoscopic neural connection atlas' international big science program." ”

In 2018, Liu Zhen became the youngest research group leader of the Institute of Neuroscience - without any overseas study background, he was hired as the leader of the research group, researcher and doctoral supervisor of the Institute of Neuroscience, and established an independent laboratory.

Liu Zhen's unusual employment has triggered extensive discussions on the evaluation system for local scientific research talents, such as "heroes ask no questions about provenance", "whether talents have the distinction of 'earth and ocean'", "scientists rely on their abilities or by titles". However, there is no doubt that the unique scientific research growth experience of Liu Zhen, a "soil postdoctoral fellow", has inspired many local young scientists to choose to stay in China for further study.

The laboratory has been established for nearly 3 years, Liu Zhen and team members have deeply cultivated the construction of genetically modified disease monkeys and tool monkey models, formed a number of innovative research results, and created a unique scientific research IP: In 2019, the laboratory used the established somatic cell nuclear transplantation technology to obtain for the first time 5 rhythm disorder clone monkey models with BMAL1 gene mutations with the same genetic background, providing a more advanced animal model for the research and treatment intervention research and development of rhythm disorder-related diseases. Last year, the laboratory published a number of high-level research papers in journals such as Cell Research.

Today, Liu Zhenhe and more than 20 young researchers in the laboratory are still working hard to promote the screening and research and development of brain disease drugs, the analysis of brain cognitive functions and the research and development of brain-like devices in the world, and are committed to creating more "Made in China" in the field of somatic cell cloning, helping China occupy an important place in the field of brain science with fierce competition in the future.

China Youth Daily, China Youth Network reporter Wang Shanshan Source: China Youth Daily

Source: China Youth Daily