Beijing time, January 10, 2020 afternoon news, this morning, 2019 “China’s top 10 progress in life sciences” press conference held in China Science and Technology Hall. At the press conference, the relevant leaders of the Chinese Association of Science and Technology Life Sciences Association introduced the selection of “Top Ten Progresses in Life Sciences in China” and the highlights of this year’s selection activities.
Since 2015, the Chinese Association of Science and Technology Life Sciences Association consortium to “fair, just and open” as the principle of the annual “China’s top ten progress in life sciences” selection process, aimed at promoting life science research and technological innovation, fully display and publicity of China’s life sciences in the field of major scientific and technological achievements. At present, the Chinese Association of Science and Technology Life Sciences Association has carried out five annual selection series of activities, the Chinese Association of Science and Technology fully affirmed and actively supported, and won the attention of all sectors of society. After the annual announcement of the results, selected project experts are invited to write and publish popular science books, and hold exchanges and science conferences for young people, to reveal to the public the new mysteries of life science, to provide new ideas for the development of new life science technologies, new breakthroughs in medicine and the development of biological economy, greatly improving the social impact of life sciences.
In 2019, the Chinese Association of Science and Technology Life Sciences Association consortium continued the previous year’s “China’s Top Ten Progresses in Life Sciences” selection method innovation, the project results of the knowledge innovation category and technological innovation category classification selection, hoping to guide science and technology workers in the field of life sciences to realize that Innovation in research methods and tools is as important as theoretical innovation. The results of this year’s project were recommended by the Association of Members of the Society of Life Sciences of the Chinese Association of Science and Technology, selected by peer experts in the fields of life sciences, biotechnology and clinical medicine, which are dominated by academicians of the two faculties, and reviewed by the Bureau of the Society of Life Sciences of the Chinese Association of Science and Technology. Finally, the results of 7 knowledge innovation categories and 3 technology innovation projects are the “Top Ten Progresses in Life Sciences in China” in 2019.
The Chinese Association of Science and Technology Life Sciences Association jointly reflects the results of the 2019 “Top Ten Progresses in Life Sciences in China” (ranked in no particular order).
Cracking the mystery of the supermolecular structure and function of diatom photosynthesis protein
Photosynthesis provides energy and oxygen for the survival of almost all living things on Earth. Diatom is an important aquatic photosynthesis organism that contributes 20% of the Earth’s primary productivity per year and plays an important role in global ecological change and carbon cycle, which is closely related to the structure and function of diatom photosynthesis systems and photosynthesis proteins.
Shen Jianren, Institute of Plant Research, Chinese Academy of Sciences, For the first time in the world, the yanting cloud research team analyzed the high-resolution structure of diatom-capture antenna membrane protein (FCP) 1.8 E, and further analyzed the electromirror structure of diatoms photolitanyr system II and FCP super complex 3.0 E, first solved the mystery of diatom photosynthesis protein supermolecular structure and function, and clarified the high-efficiency capture of diatom supermolecular structure and function of diatoms The mechanism of blue-green light, efficient transmission and conversion of light energy and light protection provides new ideas and strategies for artificial simulation of photosynthesis and guidance and design of new high-gloss crops. The results of the research have been highly praised by experts at home and abroad, and the scientific journal commented on the two work as a milestone in understanding the structure and function of photosynthesis biocapture systems.
Both results were published in the journal Science (2019, 363: eaav0365; Science, 2019, 365:eaax0446).
The overall structure of the photosystem II of diatoms and the FCPII super complex of the optical antenna protein
The Evolution of the Ruminant Genome and Its Enlightenment to Human Health
Ruminants, including cattle and sheep, are not only of great significance in the origin of human civilization and modern food safety, but also have important implications for human health with their unique evolutionary characteristics.
In conjunction with several units at home and abroad, Wang Wen’s research team at Northwestern University of Technology expounded the long-disputed history of ruminant evolution, analyzed the genetic basis of ruminant uniqueness, explored the genetic basis of rapid antler regeneration and deer’s ability to fight cancer, and revealed the molecular mechanisms of reindeer circadian rhythm loss, high-efficiency vitamin D and calcium metabolism. The study explores and explores new ways to study major life phenomena, expounds the mechanismof of ruminant evolution and extreme environmental adaptation, and is of great significance to the study of health medicine such as organ regeneration, anti-tumor, rhythm disorder and osteoporosis.
The results were published simultaneously in the journal Science (Science, 2019, 364: eaav6446; Science, 2019, 364: eaav6335; Science, 2019, 364: eaav6312).
The Mechanism of Adaptation of Ruminants to Evolution and Its Enlightenment to Health Medicine
Realized the visual ability of the naked eye infrared light and infrared image of mammals
The sense perception ability of human and animal is limited by the physical and chemical conditions of the living body itself, and expanding the limit of perception has always been the goal of human exploration. Mammals perceive light with a spectral range of 390-760 nm, and near-infrared light with wavelengths greater than 760 nm cannot be perceived by mammals, while color blindness is also a disease caused by light-sensitive spectral defects.
Xue Tian Research Group of China University of Science and Technology, in collaboration with hangang Research Group of Massachusetts State University of the United States, combined with visual neurobiomedical and innovative nanotechnology, uses up-converted nanomaterials that absorb infrared light and convert it into visible light, and imports it into the animal retina to anchor it toward sensing cells. For the first time, the ability of animal naked eye infrared light perception and infrared image vision is realized. The study has potential applications in encryption, security, human-computer interaction, and the treatment of visual disorders such as color blindness, and the delivery of eye drugs.
The results were published in the journal Cell (Cell, 2019, 177:243-255).
Mice injected with up-converted nanoparticles gained infrared light perception and infrared image vision
Single base gene editing causes a large number of off-target effectand and its optimization solution
CRISPR/Cas9 and its derivative single base editor have been widely used in life sciences and medical research. However, the off-target risk caused by gene editing hinders the application of this technique in clinical practice.
Yang Hui Research Group of the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences, in collaboration with Li Yi, Research Group of the Institute of Nutrition and Health of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences, and the Zuo Erwei Research Group of the Shenzhen Genomics Research Institute of the Chinese Academy of Agricultural Sciences, established a new generation of gene editing tool off-target detection technology – GOTI. And using this technique, it was discovered that there was a serious and unpredictable PROBLEM of DNA off-targeting in the previously widely considered safe single base gene editing technique. The technology further expands off-target detection to RNA levels, and finds that there are a large number of RNA off-targets in both commonly used single-base editing techniques, and through the transformation of single-base editing tools, screening to a new generation of high-fidelity single-base editing tools that retain efficient single base editing activity without creating additional off-targets, It provides an important basis for the application of monobase editing to clinical treatment.
The findings were published in the journal Science (2019, 364:289-292) and Nature (2019, 517:275-278).
Target effect and off-target effect of cytosine monobase editor
New solutions to improve the efficacy of nasopharyngeal cancer in the middle and late stages
China is a high incidence of nasopharyngeal cancer, accounting for half of the world’s new cases, poor treatment results, low five-year survival rate. New treatment options are urgently needed to improve patient survival.
The research team of Ma Jun of The Cancer Prevention and Control Center of Zhongshan University carried out the cutting-edge technical research of the new program of “Jixi Tabina-Cisplatin”, which used Jixi Tabinin to suppress negative immune molecules and coordinate to enhance the anti-cancer effect of cisplatin, treated the patients with better physical fitness before radiotherapy and was able to successfully complete chemotherapy, and established “Jixi Tabina and Cisplatin” A new strategy for combined chemotherapy with two drugs. Professor Ma led 12 sub-centers across the country, and a prospective clinical trial found that the therapy reduced the risk of recurrence by 49 percent, increased the three-year tumor-free survival rate by 8.8 percent (76.5 percent to 85.3 percent) without increasing toxicity. Thus, a new system of high-efficiency and low-toxic ity of nasopharyngeal cancer has been established, and a new standard of leading cutting-edge technology has been formed.
The results were published in the New England Journal of Medicine (2019, 381:1124-1135).
New strategy for combined chemotherapy for “Gisithabin e. Cispine” (reduces the risk of recurrence of nasopharyngeal cancer by 49% and increases tumor-free survival by 8.8% in 3 years)
Reveal the targets and mechanisms of new anti-TB drugs and the discovery of potential new drugs
Tuberculosis is a deadly disease caused by mycobacterium tuberculosis infection, which is the “number one killer” of infectious diseases, so research on new drug targets for TB bacteria and new drug research and development are urgent. Membrane protein MmpL3 plays a key role in the cell wall synthesis process of Mycobacterium branchicosis and is an important target for the development of new anti-tuberculosis drugs.
Under the leadership of Rao Zi and academicians, Zhang Bing, Yang Haitao and Li Jun of the shanghai University of Science and Technology research team took the lead in analyzing the high-resolution crystal structure of the drug target MmpL3 and “drug target-drug” complexes in the world for six years, revealing the working mechanism of MmpL3 and the new molecular mechanism of the new drug SQ109 to kill bacteria. The team also found that a weight-loss drug, Limonaban, was also targeted at MmpL3 inhibitors and clarified its mechanism of action. This study outlines for the first time how small molecular inhibitors accurately target the three-dimensional image of MmpL3 and its superfamily proton circulation channel, opening up a new way for the development of new antibiotics, solving the increasingly serious problem of bacterial resistance, and also laying an important foundation for the research and development of new anti-tb drugs with independent intellectual property rights in China. The research-designed anti-TB pilot drug has been patented for PCT.
The results were published in the journal Cell (Cell, 2019, 176:636-648 e613).
Structure of the drug target protein MmpL3 in active (left) and inhibitory (right) state
Molecular mechanism of four inhibitors to accurately target MmpL3
LincGET asymmetric expression triggers fate selection of embryonic cells in mice in 2-cell stage
At what time does the first choice of cell destiny occur in the development of the fertilized egg to mammalian individuals with more than 200 cell types? How did this choice happen? This is a very basic problem in life science research.
Zhou Qi, a researcher at the Institute of Zoology of the Chinese Academy of Sciences, and Li Wei’ research team found that during the mouse 2-cell embryo period, the choice of the fate of the fissure gene development had already been biased. It is also revealed that this bias comes from the unequal expression of long non-coding RNA (LincGET) associated with an endogenous retrovirus in the 2-cell cleavage sphere, prompting the fate of the intracellular cell group (inner mass, ICM) of the subcellular selection with higher LincGET expression. For the first time, this work pushed the choice of the first cell destiny differentiation to the 2-cell embryo period, which laid an important foundation for exploring the omnipotent regulation of early embryos and the mechanism of the first cell destiny differentiation. At the same time, the study also provides new ideas for studying the function of endogenous retrovirus sequences and long non-coding RNA in early embryos.
The results were published in the journal Cell (Cell, 2018, 175:1887-1901).
LincGET is unevenly expressed between two fission splints during the 2-cell period, regulating cell destiny selection through CARM1
Molecular map established by the space-time transcription group and the cell lineage of the three embryo layers in early embryos in mice
Embryonic development begins with the outer, middle and inner three embryo layers of the early embryo, but the source of these three embryo layers and their molecular regulation mechanism have been unclear.
In collaboration with Han Jingdong Research Group of the Institute of Computational Biology of the Chinese Academy of Sciences-Map Society and Peng Guangtun Research Group of the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences, the Jing Nai-chi Research Group of the Shanghai Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences worked together to construct a high-resolution space-time transcription group map of early embryos in mice. It is revealed that the dynamic changes of cell lineage and multi-energy in time and space and its regulatory network of three-embryo layer differentiation are revealed, and a new source of the occurrence of endoderm genealogy is revealed at the molecular level for the first time, and a new view that the outer embryo layer (Ectoderm) and the mesoferm (Mesoderm) have common precursors. A new theory of cell lineage differentiation in early embryo stoma was established. This work is a major revision and complement to the theory of the classical developmental biology hierarchy, which will greatly advance the development of early embryonic development and stem cell regenerative medicine.
The results were published in the journal Nature (2019, 572:528-532).
Early embryonic space-time transcription group and three-embryo cell lineage in early embryos in mice
Study on the structure and function of plant disease-resistant small bodies
Crop pests and diseases are a major threat to agricultural production in China and around the world. The big question of how the disease-resistant gene makes plants resistant to disease has not been answered since it was first isolated and identified in the 1990s.
The research team of Chai Jijie of Tsinghua University, the research team of Zhou Jianmin of the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences and the research team of Wang Hongwei of Tsinghua University worked closely together to analyze the three-dimensional structure of the disease-resistant protein ZAR1 multiple state complexes, and to clarify the disease-resistant protein after the detection of pathogenic bacterial signals, How to quickly change from resting state to activation mechanism, the first international discovery of plant disease-resistant small body protein machine, for the first time revealed the disease-resistant protein as a molecular switch, in the cell membrane control plant defense system mechanism. The research results have been highly evaluated by experts at home and abroad, and considered to be a milestone in the field of plant immunity, which has laid a key theoretical foundation for the design of a broad spectrum and long-lasting new disease-resistant protein and the development of green agriculture.
The results were published back-to-back in the journal Science (Science, 2019a, 364: eaav5868; science, 2019b, 364:eaav5870).
Living pattern map of plant disease-resistant protein ZAR1
Using single-cell multihiste techniques to analyze the bed-making process of human embryos
In collaboration with the Qiao Jie Research Group of Peking University’s Third Hospital, the Tang Fufu Research Group of Peking University reconstructed the bed-carrying process of human embryos for the first time using high-precision single-cell transcription group and DNA methylation group map, and systematically revealed the core biological characteristics and key regulatory mechanisms of this important developmental process. The study found that the three main genealogies of embryos (upper embryo layer, primary endoblast layer, nourishing exoblast) gradually showed their own unique gene expression characteristics during bedtime, suggesting that the embryo initiated the mother-to-child connection preparation state in this major developmental event. Found that during bedtime female embryos start and gradually show the trend of random inactivation of the parent or parent X chromosome, while the doubling of the dose of the X chromosome gene expression in the absence of life has been initiated in both female and male embryonic cells; Their unique DNA methylation characteristics were quickly obtained during bedmaking, indicating that DNA methylation plays an important role in maintaining the development of a particular cell spectrum.
The results were published in the journal Nature (2019, 572:660-664).
In vitro reconstruction of the bed-making process of human embryos and the mechanism of gene expression regulation