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Yang LIU: Aggressive dedication from an observer of nature to a virology fighter over the past three decades



LIU Yang

Junior Principal Investigator

Institute of Infectious Diseases

Research Area:

1. The genetic evolution study of Emerging and Re-emerging Infections Diseases (EIDs).

2. The pathogenesis of severe viral diseases and molecular mechanism of viral transmission.

3. The development of new strategies for the prevention and control of EIDs.

He won the first prize in the National Biology Olympiad on behalf of Wuhu City when he was 15.

He was preferentially admitted to the School of Life Sciences Fudan University at the age of 17

He received the Ray Wu Prize (honored as the top award for Chinese PhD students in biology) at age 33.

Aged 37, he is now a Junior Principal Investigator at the Institute of Infectious Diseases in Shenzhen Bay Laboratory. He has published 20 scientific and research articles in top international journals as the first author and co-first author, including four articles in Nature, one article in Cell and two articles in NEJM, with a cumulative impact factor of over 580. His articles have been cited for more than 4,500 times accumulatively.

Here it seems to be another enviable story of "other people's child"; however, there are far more twists and turns on his way behind glamor than we have thought.

"I have been rejected from graduate schools several times.” Liu Yang pushed up his glasses and said with a smile, "My undergraduate GPA was not enough to get a postgraduate recommendation."

01 Sunshine always comes after the storm

Recalling the setbacks and frustrations, Liu Yang looked relaxed with a peace of mind. After graduation from the university in 2006, he worked for different research institutions in Hong Kong, Shenzhen and Beijing while applying for a doctoral program. In 2013, Liu Yang finally passed the doctoral program of Tsinghua University-Peaking University Joint Center for Life Sciences (CLS) and joined Cheng Gong's Laboratory to start his research in virology that he has been dreaming of.

He cherished more the regained opportunity. After returning to the campus, Liu Yang was highly motivated in his work. When studying Zika virus, he quickly completed the preliminary cell experiment in vitro and discovered the key reason why American-lineage Zika virus had stronger infectivity than Asian-lineage Zika virus. For further verification of the experimental result in animals, he needed transgenic mice with interferon receptors knockouts. The long process of importing mice from abroad would seriously affect the experimental progress. Liu Yang and his colleagues began to consult domestic research articles thoroughly and finally found this mouse strain used by an institute in Shanghai. With the help of the mentor, the research group successfully obtained the transgenic mice. The research findings were published in Nature in 2017, which was the first CNS in Liu Yang's life. "I was very excited at that time, and I also felt relieved to complete my self-salvation psychologically." Looking back, Liu Yang sighed with mixed feelings, "This experience has had a great influence on me. It has helped me build my own set of scientific research thinking, and more importantly, it has strengthened my confidence in myself."

“My way ahead is long with no ending, yet up and down I’ll search with my will unbending." Liu Yang wrote this sentence on his personal homepage. The academic career will not end because of one setback, nor will it be immortalized because of one glory. "My fate with the biology has started from my childhood." 

02 Great ambition starts at an early age

"I like to observe all kinds of different plants and animals and think about why there are so many colorful flowers and plants in the world and why there are various animals of different shapes. When I was a child, I watched different kinds of ants fighting for food in my grandmother's yard. I used different food to lure them and put various obstacles on their marching way to observe their reactions. Sometimes I squatted all afternoon. when I came to myself, my legs went numb and the sun set."

Interest is the best teacher. Liu Yang took part in the National Biology Olympiad in high school and won the first prize, by which he was preferentially admitted to the School of Life Sciences Fudan University. When he was an undergraduate, he had the opportunity to enter the laboratory and get access to the microscopic world under a microscope. "I was fascinated by various tissues, cells and unicellular organisms at the microscopic scale.” What mysterious force drives these simple cells to build plants and animals of different shapes and eventually form a colorful biosphere? With such a curiosity, Liu Yang devoted himself to the study of molecular biology, cell biology and microbiology. He was even more amazed at the exquisite combination of nucleic acids and proteins at a microscopic scale, which together form the cornerstone of life in nature.

"With the accumulation of biological knowledge, I have the idea to explore the ultimate mystery of life. Viruses are the simplest organisms in the world, and they have made the most of basic elements in theirselves. If we want to uncover the mysteries of life, we should use viruses as starting points." For the ideal that I hold dear to my heart, I’d not regret a thousand time to die. Since then, Liu Yang has strengthened his goal and persevered in virology-related researches. Despite the twists and turns, he has always stayed persistent to strive only for the answer in his true heart.

03 Perseverance makes a difference

Raged COVID-19 broke out in 2020. Virology laboratories around the world worked hard overtime to study the pathogenesis of COVID-19 and obtain the first-hand information on development of vaccines. Liu Yang was then engaged in postdoctoral work at the University of Texas Medical Branch. He immediately set out to build a reverse genetics system for COVID-19 to rescue live novel coronaviruses with clean genetic background for studies on viral genetic evolution and protection efficiency after vaccination. In order to race against the virus, associates from the research group worked in three shifts to push forward various experimental efforts. However, the live coronaviruses rescued in the early stage always had various random mutations. No matter how they changed the construction strategies, they couldn’t get a virus that was completely consistent with the expected virus sequence. The constant repetitions and intense experiments made people fell tense and stressed, so in this case some undetermined voices were heard in the team.

Liu Yang calmed down and reflected on the experimental process -- designed with a definite purpose and a clear idea, the experiment itself was not technically difficult. Why couldn’t they still achieve a satisfactory result? After repeated reflection, he decided to re-check all the details of the whole experiment. Through careful comparison of the experimental records and communication with associates in the laboratory, he found that 2 months ago, other people in the laboratory had encountered the similar problem in the construction of Zika virus. After careful searching, it turned out that the laboratory had changed a new brand of nucleic acid dye at that time. He deduced that the new nucleic acid dye contained some chemical impurities, which caused nucleotides damage during the experiment and thus contributed to the abnormal data. He immediately changed the nucleic acid dye, and finally the experiment got back on track. After hard work for hundreds of days and nights, the research group identified several important mutational sites affecting the infection and transmission of COVID-19 during the epidemic, elaborated the laws of genetic evolution of COVID-19, and detected the changes in ability of antiserums in patients immunized with COVID-19 vaccines to neutralize many different COVID-19 variants, to provide the first-hand information for development and improvement of vaccines. The related research findings were also successfully published in top journals, such as Nature, Cell and New England Journal of Medicine. From this incident, Liu Yang has deeply realized that conducting scientific researches requires extraordinary persistence and patience in addition to strictness. "Keep calm in every event!” It tells us that if we remain calm and stay persistent in the face of setbacks, we will surely embrace the bright sunshine after going through difficulties and obstacles!

04 Stand in the Bay Area for well-established development

In 2021, Liu Yang joined the Institute of Infectious Diseases in Shenzhen Bay Laboratory, working as a Junior Principal Investigator to continue deep exploration in the field of virology. With its focus on major viral infectious diseases of the human, the research group studies the laws of genetic evolution and pathogenesis of highly pathogenic viruses, analyzes the causes of changes in viral infection and transmission abilities and illuminates their molecular mechanisms, and specially develops novel prevention and control strategies for viral infectious diseases.

The research group will try to identify important factors that potentially affect the viral fitness both on viruses and in hosts with the help of various bioinformatics analysis methods, conduct functional verification through animal models that mimic the real life cycle of viruses in nature as much as possible, build genetic engineering tools designed for various live, attenuated and non-toxic viruses by means of reverse genetics, and introduce the mutation and reporting systems required for basic researches on viral pathogenesis and screening and evaluation of virus-neutralizing antibodies, vaccines and drugs.

"I hope that we can build multiple experimental platforms for viral research in this field and establish a well-staffed research team to carry out basic research, transformation and application related to the virology. All associates in the team trust and help each other, becoming brothers willing to back each other in the battlefield.” Speaking of his prospects for the future, Liu Yang said with great expectation, "I hope to analyze the laws of coevolution of viruses and multiple hosts over millions of years and develop a variety of tools and methods for virology applicable to different basic scientific research and clinical treatment scenarios by deeply studying the survival strategies of various viruses, and ultimately explore the mysteries of cells and life with the help of viruses.”

Shenzhen Bay Laboratory is filled with full-time young PIs from various disciplines. In meeting rooms and cafes, heated discussions and thunderous applause echo here and there, and the joy of free exploration and the prospect of crossover studies unfold like a picture. Liu Yang can often be seen in crowded academic salons. Whenever he talks about the basic research, application and transformation in viology, his eyes still shine as before. As 30 years have passed, he is still the child in his grandmother's backyard, observing the mysteries of life with fascination and dancing with excitement for the occasional miracles in nature.