Reported by: Wang Ji
Translated by: Qiao Xuechao
Edited by: Garrick Jones
On 12 June, Science and Technology Daily conducted an exclusive interview with Professor Huang Zhiwei of HIT, the president of the School of Life Science and Technology on the topic of Huang Zhiwei－Installing A “Safety Valve” on Gene Editing System.
Huang Zhiwei, born in May 1979, is the president of the School of Life Science and Technology. He has devoted himself to the fundamental researches of immunity and infection over a long period of time, including the researches on structure and function between AIDS and protein complex, and the molecular mechanism of bacteria adaptive immune system.
“7-11” is known by all the people who know Huang Zhiwei. For many years, Huang Zhiwei has worked from 7 a.m. to 11 p.m.
Though having worked in this field for such a long time, Huang Zhiwei still has the feeling that he doesn’t have enough time for work. He leaves an impression of “fast pace” on his colleagues and students. Lately, the good news of publishing his paper in Nature didn’t slow him down.
“What’s the first question?” Huang Zhiwei cannot wait for the journalist to raise a question, so he asked.
He is an interdisciplinary “player”
Dozens of Nature, Science and Cell magazines spread out on the desk of Huang Zhiwei’s laboratory. He insists on sparing time to read literature and documents every day, and international top academic journals are indispensable.
This “7-11” professor majored in chemical engineering and technology during his undergraduate studies. What his teacher said opened his door to biology, which is “If you are interested in organic chemistry, you will be more interested in life chemistry”. During his undergraduate studies, Huang Zhiwei began his self-study on cytobiology, genetics, biology and other theories. At the stage of postgraduate and post-doctor studies, he successively engaged in the structure and function of life science, and immunity and infection.
“The more you emphasize on application, the more difficult in doing scientific research. Scientific research cannot be too utilitarian”. The fundamental research that Huang Zhiwei and his team engaged in may be derived from their purity in life science.
On January 2014, Huang Zhiwei and his team revealed the AIDS Vif structure, and the paper AIDS Vif “Hijacks” CBF-β and the Molecular Mechanism of CUL5 E3 Ligase Complexes was published in Nature magazine.
As a Chinese proverb goes, “Know the enemy and know yourself and you can fight a hundred battles with no danger of defeat.” Huang Zhiwei said that if you want to destroy your enemy, which is AIDS virus, you have to figure its details out.
This research clarified that how Vif “hijacks” the molecular mechanism of immune cells, and it laid the structural foundations for the development of anti-AIDS drugs. Huang Zhiwei recalled, “After publishing this research, many AIDS patients called to consultant, and it seems like this research is a life-saving straw”.
However, it has been less than two years since he organized HIT Structural Molecular Biology and Natural Immune Signal Transduction Laboratory from zero-start.
Hearing the roar of laboratory apparatus and looking at the tins and bottles and large-scale testing equipments all over the house, Huang Zhiwei said, “I gradually fill in this empty house from a desk and a test tube.”
What does the 3D structure of AIDS virus Vif looks like? This is a question troubled this field for over 30 years. However, this team of 15 people broke through this tough issue in only a little more than a year. Huang Zhiwei told the journalist, there are countless procedures in one experiment, and different problems may occur in each step. However, it may come to nothing if there is one mistake in one step.
According to what Huang Zhiwei said, he never considers how many people working in this field, and how many people failed. “This may influence your judgment and good research is never achieved by planning.” This interdisciplinary “player” with a southern accent is smartly dominating the international stage, carrying a young heart.
Not being a walking-away shopkeeper
The wall of his office is posted a pile of pink sticky-notes. Huang Zhiwei said, “Doing scientific research is different from office workers who work from 9 a.m. to 5 p.m. You carry new expectations when you come to the laboratory every morning.” Compared with the time spent at laboratory, the time Huang Zhiwei spent at home is not worth mentioning. According to what he said, it’s hard to change a good habit.
Scientific researchers are like athletes, the best period of one’s career is very short. However, Huang Zhiwei undoubtedly steps into a “positive cycle”.
On April 2016, his team revealed the working mechanism of Cpf1 (Cpf1 is a kind of effect protein of CRISPR bacteria immune system, and now it has been used as new type of gene editing tool). The paper－The Crystal Structure of Cpf1in Complex with CRISPR RNA published on the Nature.
Now, scientists have initially understood that some diseases are due to the disorder of DNA sequences. However how to specifically change and manipulate this kind of DNA, human beings are still have no idea.
This kind of disease-causing DNA is the “killer” of cancer, AIDS and other diseases. However, CRISPR-Cpf1 can repair this “defective” DNA. The point is that the molecular mechanism of CRISPR-Cpf1 cannot be revealed for a long time.
The reveal of CRISPR-Cpf1’s operating mechanism has important scientific significance relating to the molecular mechanism of bacteria’s resistance to virus invasion through the CRISPR-Cpf1 system. Moreover, it has laid a structural foundation for scientists to further modify Cpf1 system, and make use of it as a wholly new gene editing system. Scientists will be a step closer to defeating cancer and AIDS.
Huang Zhiwei vividly compares Cpf1 gene editing system to “gene scissorhands”, which is a first for a Chinese person to analyze this kind of gene editing system.
Huang Zhiwei said directly that it is meaningless to be an employer-contractor in scientific research. He thinks that professors with rich experience in scientific research should be more diligent than students. They cannot become “walking-away shopkeepers”. “Professors are the most familiar with their own laboratories. They should operate the important experiments by themselves and personally observe each experiment”, saying this, he signed the files given by his students.
“He always wears stubble of untrimmed beard due to no time to shave. He doesn’t care about his image, but he especially cares about students’ experiments. He will personally demonstrate the actions and procedures of experiments. He even looks at my testing notes and criticizes my mistakes.” One of Huang Zhiwei’s students told the journalist.
It’s enjoyable to do scientific research
On 28 April, the relevant research outcomes about the reveal of streptococcus gene editing “braking system” molecular mechanism by Huang’s team published on the Nature again.
“The magazine is only a carrier, and people should attach importance to the outcomes.” Though having published many papers on the Nature, he still behaves modestly.
This paper revealed the molecular mechanism of inhibition streptococcus activity by an anti-CRISPR protein AcrIIA4. It helps to reveal the co-evolution molecular mechanism of the bacteria immune system and the bacteriophage defense system, and it laid a structural foundation for accurately controlling streptococcus gene editing activity.
In Huang Zhiwei’s opinion, gene editing may redraw the blueprint of human beings. But people should notice that people can use gene editing system, but at the same time, they should take control of using it to reduce negative effects of gene editing “off-targeting”.
“You can compare the streptococcus SpyCas9 gene editing system to a ‘missile’, then RNA is like a ‘guiding system’ which is responsible for guiding the missile to the target. Streptococcus SpyCas9 nuclease is an ‘explosive material’ which used to destroy the target DNA”. Huang Zhiwei told the journalist that when gene editing becomes “off-target”, this “missile” may have a chance of losing control.
For many years, as kept a habit of “7-11”, Huang Zhiwei didn’t feel tired, but was always saying, “I don’t feel tired, I think that maybe all the people who engaged in scientific research are all the same kind.”If students didn’t see him at office, they will curiously asked, “Where did Teacher Huang go? It’s not his style!”
Insisting on working in this field for more than ten years as one day, what drives Huang Zhiwei is internal enthusiasm. His students told the journalist: “Teacher Huang will talk without ceasing when talking about life science and one or two hours are not enough.”
In his view, it’s enjoyable to do scientific research. “You will discover new things, and we are the first one to know this, isn’t cool?” He said.