Wuda Song Baoliang team: in scientific research "no man's land" to explore new paths

September 11, 2020,
General
presided over a symposium of scientists and delivered an important speech stressing that the vast number of scientific and technological workers should set up the ambition of daring to create, dare to put forward new theories, open up new fields, explore new paths, and work hard in originality.
In today's overnutrition, cardiovascular disease has become the "number one killer" threatening human health, and cardiovascular disease is most associated with low-density lipoprotein cholesterol (LDL-C) in the blood. Exploring the control level of LDL-C in the human body has become the goal of countless scientific research teams all over the world.
in Wuhan University, there is such a research team. Over the years, they have been sleeping around the night, persistent pursuit, in the field of cholesterol and lipid metabolism has made a series of original discoveries, their research results are included in more than a dozen English textbooks or monographs. They are the cholesterol and lipid metabolism research team led
Professor Song Baoliang, a professor at Wuhan University's School of Life Sciences.daily life, you may hear people around you have made similar complaints: Why do I go vegetarian for a long time, but when the physical examination found that cholesterol is high, the stomach is getting bigger and bigger? And some of the casual life, eat everything colleagues when the physical examination of the indicators are normal?
" cholesterol levels are regulated in two main ways: daily dietary lifestyle and genetic factors. Long-term intake of excessive cholesterol, leading to LDL-C elevation, easy to cause cardiovascular disease. But because there are small differences in each of our genomes, cholesterol and lipid metabolism can vary and even have a huge impact on different individuals. Song Baoliang gives an example: one person eats a dozen eggs a day for ten years, and after many years cardiovascular function is still normal, while another person eats a dozen eggs a day, only a year later developed atherosclerosis. Why are there two very different endings? Uncovering the scientific laws behind these everyday phenomena is an important exploration direction for the cholesterol and lipid metabolism research team.
to solve these problems, naturally can not be separated from a large number of scientific research work. "But for our team, there are few ready-made theories or tools because the tasks they undertake are basically in the 'no man's land'. This requires team members to think about problems that others have not solved, and to learn to 'make bold assumptions and be careful to prove them'. Song Baoliang said.
, the team ventured to guess whether there was a new cholesterol-regulating gene. With this in mind, the team, in collaboration with Professor Ma Yixuan of Xinjiang Medical University, discovered a family of low-cholesterol Kazakh families, some of which had significantly lower blood lipids than normal, but were healthy. Using genome-wide exon sequencing and gene association analysis, the researchers found a new cholesterol absorption regulatory gene, LIMA1. They constructed genes to knock out mice, proving that after the loss of the LIMA1 gene, the animals' cholesterol absorption in the diet decreased significantly.
June 2018, Science, a leading international journal, published the team's findings in the form of a long-form study. The industry believes the discovery scientifically explains differences in cholesterol absorption in the body and suggests that people can achieve healthy lipid reduction by inhibiting the function of LIMA1.
"Although LIMA1 was discovered, it is the team's next study to understand the causal relationship and mechanism of action between it and cholesterol as early as possible." Liu Yong, a team member and professor at Wuhan University's School of Life Sciences, said the team has conducted more in-depth research to provide new drug research and development targets for cholesterol reduction as early as possible.November 2, 2019, the first Scientific Discovery Award Ceremony was held in Beijing, where 50 young scientists from nine fields were awarded, each winner will receive a total of 3 million yuan for five consecutive years, with Song Baoliang among them. Song Baoliang's award is due to affirming his cutting-edge achievements in the mechanisms and functions of cholesterol absorption, synthesis, transportation and co-price modification, and encouraging him to continue to explore the basic areas of cholesterol and lipid metabolism.
the word "exploration" sounds light, but it means paying for efforts and sweat that no one can imagine. "The more original and unknown the team is, the more unknown it is. Don't be afraid of difficulties, rest assured to venture forward. As long as it's about human health, you have to do it. Song Baoliang said.
returned to China in 2015 to join the team, Wang Wei, a professor at Wuhan University's School of Life Sciences, has always worked in the lab for more than a dozen hours a day, even on holidays. "It's the norm for everyone on the team." "People never cry bitter, don't call tired, and are obsessed with clearing the scientific link between genes and disease, " Wang said. It has always been said that as long as one of the results of the study at hand translates into a new generation of cholesterol-lowering drugs, it means that years of hard work are not in vain. "
" everyone every moment in a hundred times the effort, are constantly out of their comfort zone. Song Baoliang said with emotion, over the years, in order to crack more mysteries in the human body, team members have always adhered to the "two obsessive", that is, whether it is experimental data indicators, or the completion of the project indicators, are committed to the data to do more accurate, are committed to digging the subject deeper.
March 20, 2020, cell Research, an authoritative international journal, published the latest research results of Wang's team. For the first time, the team found g protein-coupled GPCR, which directly regulates blood cholesterol levels. GPCR is highly effective, with more than one-third of all drugs on the market targeted at GPCR, and this study provides a new and important target for cholesterol-lowering drug development.
" Professor Song Baoliang has a mantra: to become a useful person, to become a spiritual pursuit of people. Since joining the team, I've seen him as the hardest worker and the first and last person to go to the lab. In him, I saw a love of scientific research and the pursuit of career. Wang said.epidemiological study found that in today's increasingly rich material life, the offspring of obese mothers are not only often obese, but also accompanied by tumors and high rates of cholesterol and lipid metabolism, a condition known as fetal disease.zheng Ling, a member of the
team and a professor at Wuhan University's School of Life Sciences, found that maternal obesity plays an important role in the development of metabolic diseases in children: cholesterol and lipid metabolic diseases are more serious when the children of obese mothers are overnourished.
" we focused on the interaction between different human tissues, and identified and studied some of the secretion of new factors. We are exploring the feasibility of using it as a drug target, which promises to bring new light to the treatment of cholesterol and lipid metabolism-related diseases. Zheng Ling said.
", not only the super-worldly talent, but also the perseverance of the people. "Over the years, in order to reveal more metabolic mysteries, early access to research results to serve the health of the whole population, the team in research methods and ideas continue to innovate. Despite the difficult process, breakthroughs have been made: new paths to in-cell cholesterol transport were discovered in 2015; cholesterol was found to be a co-priced modified protein in 2017; "protective genes" for high blood lipids were discovered in 2018; new "obesity factors" were discovered in 2019... In the field of cholesterol and lipid metabolism, an innovation is being produced in the hands of this team.
July 2020, the team developed a new topic, fat metabolism stable regulation and reprogramming. They will focus on the molecular mechanisms of lipid metabolism regulation, including cholesterol, and explore metabolite signaling molecules, metabolite transport transformation, signal transduction pathways, and communication mechanisms between organs of different tissues. At the same time, the physiological pathological functions of lipid metabolism, such as stress-causing metabolic reprogramming, are also studied at the overall level, which in turn leads to the mechanism of disease.
" currently clinical treatment of diabetes, a class of drugs, by inhibiting the kidneys in the original urine glucose re-absorption, so that glucose through the urine, such drugs have a good effect. But the current fat-lowering drugs, are to change the distribution of lipids, and did not cause cholesterol to leave the body. There will still be problems in the long run. In the course of our study, we found that after a genetic mutation, cholesterol increased significantly to the outside of bile. Currently, we are developing therapeutic antibodies with a view to achieving an effect that promotes cholesterol excretation. It is hoped that the team's research can promote domestic innovative drugs to benefit the vast number of patients as soon as possible, as soon as possible to serve the health of the whole population. "When it comes to the future, Song Baoliang is full of confidence.I am mainly engaged in the prevention and treatment of atherosclerosis in the laboratory of basic research, set up a series of large-scale genetic screening system. My mentor, Professor Song Baoliang, gave me a new topic: whether i can find a special gene that can be used as a new target for treating cardiovascular disease.
innovation comes from relentless research. Through a number of data comparisons, I quickly found a gene, with Mr. Song's research analysis, we agreed that the gene has the potential to reduce blood lipids, and participate in the clotting system, is likely to be a very perfect target for the treatment of cardiovascular disease.
, however, I was quickly defeated by reality: my research on the clotting system was entirely layman, and I had no experience with research methods or animal models.
challenges are exciting and difficult. "Can I do it?" With such doubts, I asked Mr. Song. He said to me, we do research, should pursue breakthrough, the pursuit of perfection, young hard work, do a career, to the old age will not lament this life inaction! I feel very deep about this, but also secretly determined, while now young, have the energy, it is better to let go of a hard work.
To this end, I fight day and night, consult a large number of relevant literature to establish systematic theoretical knowledge, consult experts in various fields to broaden their horizons, actively participate in various types of meetings and training, and constantly improve experimental skills. In order to make rapid and orderly progress of the experiment, the laboratory not only provides strong technical and equipment support, but also specially employs a series of auxiliary personnel such as cell culturers, animal keepers and cleaners. At present, we have shown that inhibiting the gene can significantly reduce blood cholesterol levels, resist the development of atherosclerosis plaques, and in the plaque ruptured thrombosis model we have established, inhibiting the gene has a good anticoagulant effect, preventing oversized thrombosis and blocking blood vessels. In order to get better into clinical studies, we have also designed specific inhibitors for the gene, and we have made very good progress.
with the full support of Mr. Song, I continue to overcome difficulties, work together with you to achieve a series of breakthroughs, and more and more confident in the subject of research. As the project progressed, I bent on seeing this as a promising target for the prevention and treatment of cardiovascular disease, and I hope that my research will bring good news to the vast majority of people with cardiovascular disease.
(reporter Ren Huan interview finishing)