Guangming.com (Reporter Zhao Qingjian) html On the morning of November 10, the consortium of the China Association for Science and Technology Life Sciences Society announced the "Top Ten Progresses in China's Life Sciences" in 2019. Research results such as "Cracking the mystery of the supramolecular structure and function of Diatom photosynthetic membrane protein", "Hyperforming genome of ruminants of and its implications for human health", "Realizing infrared light perception and infrared image vision capabilities in mammals" were selected.
According to reports, the results announced this time were recommended by the Member Society of the Consortium of the Life Science Society of the China Association for Science and Technology, selected by peer experts in the fields of life sciences, biotechnology and clinical medicine, mainly academicians of the two academies, and reviewed by the presidium of the Federation of the Life Science Society of the China Association for Science and Technology, and finally determined that the results of 7 knowledge innovation categories and 3 technological innovation projects were the "Top Ten Progresses in China's Life Sciences" in 2019.
Since 2015, the China Association for Science and Technology Life Science Society Consortium has carried out this selection activity for five consecutive years. After the selection results are announced every year, selected project experts are invited to write and publish popular science books, and an exchange meeting and popular science report meeting for young people will be held to reveal the new mysteries of life science to the public, provide new ideas for the development of new life science technologies, new breakthroughs in medicine and the development of bioeconomy, and enhance the social influence of life sciences.
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Cracking the mystery of supramolecular structure and function of diatom photosynthetic membrane protein
Photosynthesis provides energy and oxygen for the survival of almost all organisms on the earth. Diatoms are an important aquatic photosynthetic organism that contributes 20% of the earth's primary productivity each year and plays an important role in global ecological changes and carbon cycles. This is closely related to the structure and function of the diatom photosynthetic membrane system and photograb proteins.
Shen Jianren from the Institute of Botany, Chinese Academy of Sciences, and Kuang Tingyun research teams in the world analyzed the high-resolution structure of 1.8 angstrom light-catching antenna membrane protein (FCP) for the first time, and further collaborated with Tsinghua University's Sui Senfang's research team to analyze the electron microscope structure of diatom light system II and FCP supercomplex 3.0 angstrom, and took the lead in cracking the mystery of the supramolecular structure and function of diatom photosynthetic membrane protein, elucidating the mechanism of diatom efficiently capturing blue-green light, efficiently transmitting and converting light energy, and light protection, providing new ideas and new strategies for artificially simulating photosynthesis and guiding the design of new high-light-efficient crops. The research results have been highly praised by experts at home and abroad. The special comments on the journal Science (Science) are of milestone significance for understanding the structure and function of photosynthetic bio-light-trapping systems. Both results of
were published in Science (Science, 2019, 363: eaav0365; Science, 2019, 365: eaax0446).
The overall structure of the optical system II and light-catching antenna protein FCPII super complex
The evolution of ruminants' genome and its enlightenment on human health
Ruminants including cattle and sheep are not only of great significance in the origin of human civilization and modern food safety, but their unique evolutionary characteristics are also of great significance to human health.
Wang Wen's research team from Northwestern Polytechnical University, joined hands with many domestic and foreign units to clarify the long-standing controversial evolutionary history of ruminants, analyze the genetic basis of the unique traits of ruminants; explore the genetic basis of rapid regeneration of deer antlers and the anti-cancer ability of deer; reveal the molecular mechanisms of reindeer circadian rhythm loss, efficient vitamin D and calcium metabolism. This study explores and opens up new ways to study major life phenomena, elucidates the mechanisms of ruminants' evolution and extreme environmental adaptation, and has important implications for the research on health medicine such as organ regeneration, anti-tumor, rhythm disorders and osteoporosis.
This result was published in the journal Science in three long research articles (Science, 2019, 364: eaav6446; Science, 2019, 364: eaav6335; Science, 2019, 364: eaav6312).
The mechanism of adaptation and evolution of ruminants and its enlightenment on health medicine
Realizes the naked eye infrared light perception and infrared image vision ability of mammals
The perceptual ability of humans and animals is limited by the physical and chemical conditions of living organisms. Expanding the limit of perception has always been the goal of human exploration. The spectrum of light perceived in mammals is 390-760 nm, and near-infrared light with a wavelength greater than 760 nm cannot be perceived by mammals. At the same time, color blindness is also a disease caused by photosensitive spectrum defects.
Xue Tian's research group at the University of Science and Technology of China cooperated with Hangang Research Group of Massachusetts State University in the United States to combine visual neurobiomedicine and innovative nanotechnology, using upconvert nanomaterials that can absorb infrared light and convert it into visible light, and introduced it into the animal's retina to target and anchor it on photoreceptor cells, realizing the ability of infrared light perception and infrared image vision for the first time in animal naked eyes. The study has application potential in encryption, security, human-computer interaction, as well as the treatment of visual diseases (such as color blindness, etc.) and the delivery of ophthalmic drugs.
This result was published in the journal Cell (Cell, 2019, 177: 243-255).
Mice injected with upconverted nanoparticles obtained infrared light perception and infrared image vision ability
single base gene editing causes a large number of off-target effects and its optimization solutions
CRISPR/Cas9 and its derivative tool single base editor has been widely used in life sciences and medical research. However, the off-target risk caused by gene editing hinders the application of this type of technology in clinical practice.
Research group of Yang Hui, the Center for Excellence of Brain Science and Intelligent Technology, Chinese Academy of Sciences, and , Shanghai Institute of Life Sciences, Chinese Academy of Sciences, Li Yixue's research group of the Institute of Nutrition and Health, Shanghai Institute of Life Sciences, Chinese Academy of Sciences, and Zuo Erwei's research group of Shenzhen Institute of Genomics, Chinese Academy of Agricultural Sciences, established a new generation of off-target detection technology for gene editing tools - GOTI, and used this technology to find that the single-base gene editing technology that was generally believed to be safe has serious and unpredictable DNA off-target problems. This technology further expanded the range of off-target detection to the RNA level. It was found that the two commonly used single-base editing technologies have a large number of RNA off-targets. By modifying the single-base editing tool, a new generation of high-fidelity single-base editing tools are screened that retains efficient single-base editing activity without causing additional off-targeting, providing an important basis for the application of single-base editing in clinical treatment. The research results related to
were published in Science (Science, 2019, 364: 289-292) and Nature (Nature, 2019, 517: 275-278).
Targeting effect and off-target effect of cytosine single-base editor
New solution to improve the efficacy of middle and late nasopharyngeal carcinoma
China is a high incidence of nasopharyngeal carcinoma, accounting for half of the world's annual new cases, poor treatment effect, and a low five-year survival rate. New treatment options are urgently needed to improve patient survival.
The cutting-edge technology research on the new "gemcitabine + cisplatin" solution carried out by Ma Jun's research team at the Tumor Prevention and Treatment Center of Sun Yat-sen University. It uses gemcitabine to inhibit negative immune molecules and jointly enhance the anti-cancer effect of cisplatin. It provides treatment at the best time before radiotherapy when the patient has a good physical condition and can successfully complete chemotherapy. It has established a new strategy of combining "gemcitabine + cisplatin" with two drugs combined with chemotherapy. Professor Ma Jun led 12 branch centers across the country and found through a prospective clinical trial that the therapy can reduce the risk of recurrence by 49%, increase the 3-year tumor-free survival by 8.8% (76.5% to 85.3%), and does not increase toxicity. As a result, a new system of drug use for nasopharyngeal carcinoma is established, forming a new internationally leading cutting-edge technology standard.
This result was published in The New England Journal of Medicine (2019, 381: 1124-1135).
The new strategy of combining "gemcitabine + cisplatin" with two drugs combined with chemotherapy can reduce the risk of recurrence of nasopharyngeal carcinoma by 49%, and increase the 3-year tumor-free survival rate by 8.8%.
reveals the targets and mechanism of action of new anti-tuberculosis drugs and the discovery of potential new drugs
Tuberculosis is a fatal disease caused by infection with Mycobacterium tuberculosis. It is the "number one killer" among infectious diseases. Therefore, the research on new drug targets and new drug development for tuberculosis bacteria is imminent.The membrane protein MmpL3 plays a key role in the synthesis of Mycobacterium cell wall and is an important target for the development of new anti-tuberculosis drugs.
Under the leadership of Academician Rao Zihe, Zhang Bing, Yang Haitao and Li Jun from the research team of Shanghai University of Science and Technology took the lead in internationally analyzing the high-resolution crystal structure of the drug target MmpL3 and the "drug target-drug" complex, revealing the working mechanism of MmpL3 and the new molecular mechanism of the new drug SQ109 killing bacteria. The research team also discovered that a weight loss drug, rimonaban, is also an inhibitor , which targets MmpL3, and elucidates its mechanism of action. This study outlines for the first time how small molecule inhibitors accurately target MmpL3 and its superfamily proton influx channels, opening up a new way for the research and development of new antibiotics and solving the increasingly serious problem of bacterial resistance around the world, and laying an important foundation for my country to develop new antituberculosis drugs with independent intellectual property rights. The research-designed anti-tuberculosis pilot drug has been patented for PCT.
This result was published in the journal Cell (Cell, 2019, 176: 636-648 e613).
The structure of the drug target protein MmpL3 in an active (left) and inhibitory (right) state
The molecular mechanism of precise targeting of MmpL3
LincGET asymmetric expression triggers the fate selection of embryonic cells in the 2-cell stage of mouse
During the development of fertilized eggs to mammalian individuals with more than 200 cell types, when did the first time the choice of cell fate occurred? How did this choice happen? This is a very basic issue in life science research.
Zhou Qi's research group at the Institute of Zoology, Chinese Academy of Sciences and Li Wei's research group found that during the 2-cell embryo period of mouse, the selection of blastomere development fate has become biased, and it is revealed that this bias comes from the uneven expression of a long non-coding RNA (LincGET) associated with an endogenous retrovirus-related blastomere between blastomeres in the 2-cell phase, which prompts the fate of daughter cells with higher LincGET expression. This work has pushed the choice of the first cell fate differentiation to the 2-cell embryo period for the first time, laying an important foundation for exploring the all-purpose regulation of early embryos and the mechanism of the first cell fate differentiation. At the same time, the study also provides new ideas for studying the functions of endogenous retroviral sequences and long non-coding RNA in early embryos.
This result was published in the journal Cell (Cell, 2018, 175: 1887-1901).
LincGET is unevenly expressed between two blastomeres in the 2-cell phase, and cell fate selection is regulated by CARM1.
Molecular map established by the spatiotemporal transcriptome of the whole germ layer and the three germ layer cell lineage of early embryos in mice
Embryo development begins in the three germ layers of the outer, middle and inner embryos of early embryos, but the source of these three germ layers and their molecular regulatory mechanisms have been unclear.
Research group of Jing Naihe of Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, together with Han Jingdong's research group of the Institute of Computational Biology Partnership of Chinese Academy of Sciences-Maxford Society and Peng Guangdun research group of Guangzhou Institute of Biomedical and Health of Chinese Academy of Sciences, through the construction of a high-resolution spatiotemporal transcriptome map of early mouse embryos, revealing the dynamic changes in time and space of cell lineages and pluripotency of three germ layer differentiation and its regulatory network; for the first time, a new source of the occurrence of the endoderm lineage was revealed, a new view that the ectoderm and mesoderm have common precursors were proposed, and a new theory of cell lineage differentiation of early embryos was established. This work is a major revision and supplement to the hierarchical lineage theory of classical developmental biology, and will greatly promote the development of early embryonic development and stem cell regenerative medicine-related fields.
This result was published in Nature (Nature, 2019, 572: 528-532).
Early embryo spatiotemporal transcriptome and trigerm cell lineage of mice
Structure and function of plant disease-resistant bodies
Crop pests are a major threat to agricultural production in my country and globally. Since the first time in the 1990s, the major question of how disease-resistant genes make plants disease-resistant has not been answered.
Tsinghua University Chai Jijie's research team, Zhou Jianmin's research team from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, and Tsinghua University Wang Hongwei's research team from the three-dimensional structure of multiple state complexes of the disease-resistant protein ZAR1, and explained the mechanism of how the disease-resistant protein can quickly change from a resting state to an activated state after discovering pathogenic bacteria signals; it was the first international discovery of the protein machine of plant disease-resistant bodies, revealing for the first time the disease-resistant protein, as a molecular switch, controls the plant defense system on the cell membrane. The research results have been highly praised by experts at home and abroad, and are considered to be a milestone in the field of plant immunity, laying a key theoretical foundation for designing broad-spectrum and lasting new disease-resistant proteins and developing green agriculture.
This result is published back-to-back in the journal Science (Science, 2019a, 364: eaav5868; Science, 2019b, 364: eaav5870).
Activation mode map of plant disease-resistant protein ZAR1
uses single-cell multiomics technology to analyze human embryo implantation process
Peking University Tang Fuchu Research Group and Qiao Jie Research Group of Peking University Third Hospital cooperated with the first time to reconstruct the human embryo implantation process using high-precision single-cell transcriptome and DNA methylation group maps, systematically revealing the core biological characteristics and key regulatory mechanisms of this important developmental process. The study found that during the implantation process, the three main lineages of the embryo (epidermal, primitive endoderm, and trophoblastic ectoderm) gradually showed their own unique gene expression characteristics, suggesting that the embryo initiated the maternal and fetal junction preparation state in this major developmental event; it was found that during the implantation process, the female embryo initiated and gradually showed a tendency for random inactivation of the paternal or maternal X chromosome, and the doubling of the gene expression dose of the X chromosome that was not inactivated has been initiated in both female and male embryo cells; it was found that the three main cell lineages had similar DNA methylation patterns in the preimplantation stage, and their own unique DNA methylation characteristics were quickly obtained during the implantation process, indicating that DNA methylation plays an important role in maintaining the development of specific cell lineages.
This result was published in Nature (Nature, 2019, 572: 660-664).
In vitro reconstruction and its gene expression regulation mechanism of human embryo implantation process
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