People who "break their wrists" with microbes

Cheng Wei (center) and team members discuss the experimental protocol.

What are microorganisms? From well-known bacteria, viruses, and fungi to less familiar chlamydia and actinomycetes, these tiny organisms not only coexist with humans, but also contribute to infectious diseases. Behind this, a group of biomedical researchers have been silently playing a game with it, hoping to play an active role in the intervention and treatment of infectious diseases through research. Cheng Wei, professor and doctoral supervisor of West China Hospital of Sichuan University, is one of them.

The path to study is taught with tenacity

When he was studying, Cheng Wei was quite concerned about tuberculosis, HIV and other infectious diseases. "In real life, many people are deeply injured by infectious diseases, and in front of microorganisms, humans are sometimes powerless." Cheng Wei said, "This also prompted me to choose to study clinical pathogenic microorganisms. ”

The seeds of scientific research were planted in 2004. Cheng Wei still clearly remembers that year, the Beijing Institute of Life Sciences was established (listed in 2005), which became one of the landmark events in the development of life sciences and biotechnology in China. Cheng Wei, a graduate student at Hainan University, saw the news as he was looking for direction in the blue ocean of biology. Therefore, he took the initiative to apply and passed the tutor assessment of the institute with excellent results, and studied under Professor Chai Jijie, a leading figure in life science research in the mainland.

However, Cheng Wei's scientific research road has not been smooth. Due to his family's poverty, he interrupted his studies for two years after graduating from his master's degree, and used his work income to pay off the debts he owed to study. "In order to study, I also worked as a tutor and found a job similar to sales." The hard life did not consume Cheng Wei's will, and with the help of relatives, teachers and classmates, Cheng Wei continued to complete his studies in 2007 and eventually obtained a doctorate.

In February 2011, Cheng Wei came to Washington University in St. Louis to engage in postdoctoral work, nearly 4 years of postdoctoral career, Cheng Wei published two high-quality papers in the international top journals "Science" and "Nature - Communications" journals.

"In order to resolve the crystal structure of membrane proteases, I took several protocols, and conducted 6 months of research but basically did not make progress. The postdoctoral co-supervisor advised me to abandon the topic and concentrate on the main topic he gave me. Cheng Wei said.

Cheng Wei did not want to give up. Because once the experiment is successful, it is possible to develop new drugs as drug targets for the treatment of corresponding diseases. After another 3 months, he found that many small crystals had grown under the microscope. "I continued to work hard for 8 months, optimized more than 22,000 conditions, and finally got the experimental results."

In February 2014, Cheng Wei published the article in Science as the first author. At this point, 3 years have passed since the first research idea was proposed. "This incident gave me a lot of confidence. As long as you do anything with your heart, you will have the opportunity to do it. He said.

Constantly overcome more scientific research problems

In October 2014, Cheng Wei ended his work in the United States. "Before I went abroad, I thought I must return to China. When I was studying, I received help from many people, and I also wanted to give back what I learned to the society, help more people, and let this spirit be passed on. ”

At this time, the West China Hospital of Sichuan University threw an olive branch to Cheng Wei, "The State Key Laboratory of Biological Therapy of West China Hospital provides a good platform for me to engage in basic research combined with clinical practice. Cheng Wei said that the preferential treatment policy of the national and local governments for overseas returned scientific researchers has allowed him to have no worries and can engage in scientific research with peace of mind.

In November 2020, Cheng Wei had his own laboratory, a biosafety level II laboratory that can conduct research on clinically pathogenic bacteria. Cheng Wei, who persistently pursued the path of scientific research, also became a favorite mentor for students. Under his guidance, students have also published papers in internationally renowned journals such as Nature-Microbiology and Cell Research, and won a series of national scholarships, some of whom have become chief physicians of top three hospitals, some of whom have become university professors, and some of whom continue to stay in the team to engage in postdoctoral work.

Today, Cheng Wei's research team is also carrying out basic research around the treatment of more diseases. Cheng Wei hopes that these basic research can truly help people plagued by diseases as soon as possible. "Biomedical research is a long process that requires repeated validation, sometimes more than a decade, decades, or even a generation. But I believe that as long as we continue to study, we can eventually help others and benefit the whole society. ”

Find the key to microbial resistance

At present, infectious diseases are still a major threat to global public health, and although the treatment and vaccination of pathogens has greatly reduced the impact of infectious diseases in the past few decades, the incidence and mortality of infectious diseases remain high due to the emergence of new pathogenic microorganisms and the increase of drug-resistant pathogenic microorganisms.

Cheng Wei's job is to study the pathogenic mechanism and causes of drug resistance of microorganisms. "If we compare microbes to a lock, our goal is to study the causes of their resistance and find the key at the source." When bacteria become resistant, we have to look for a new way to control the bacteria, and then the phages can get involved. Cheng Wei told this reporter.

Bacteriophages, as the name suggests, are viruses that eat bacteria. In 2018, Cheng Wei's research team published a research paper in the sub-journal of the journal Nature, Nature Microbiology, revealing the molecular mechanism of bacteriophage lysis - the regulation of the lysate cycle. This research finding provides ideas and theoretical guidance for phages for clinical treatment, and also provides new options for solving microbial resistance.

In 2020, the Standing Committee of the National People's Congress deliberated and passed the Biosecurity Law of the People's Republic of China, which regards the response to microbial resistance as one of the eight major areas of biosecurity. The problem of microbial resistance rises to a national security issue and a major strategic component, which is of far-reaching significance. "At present, medical technology is developed, liver transplantation, kidney transplantation, heart transplantation can be achieved, but there is a huge risk of infection after surgery. In clinical treatment, some patients also develop resistance to the drug, which eventually leads to surgical failure. Cheng Wei said. Finding the key to microbial resistance can be of great help in the treatment of infectious diseases.

(Photos in this edition are provided by the interviewee)