On the morning of May 26, the third session of the Chemical Biology High-end Forum of the State Key Laboratory of Medicinal Chemical Biology was held as scheduled. This forum invited academician Shi Yunyu, a famous biophysicist and structural biologist, a member of Chinese Academy of Sciences and a member of the World Academy of Sciences, and Research Fellow Li Guohong, an international scholar of Howard Hughes Medical Institute (HHMI), Deputy Director of National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences and a recipient of the National Outstanding Youth Fund, to give online presentations. Research Fellow Gong Deshun from Nankai University, Prof. Yang Na from Nankai University, Prof. Wu Xudong from Tianjin Medical University and Prof. Weng Xiaocheng from Wuhan University participated in the seminar. The forum was conducted online and also live-streamed to the public through Research Cloud and other platforms, with a total of more than 76,000 viewers.
The title of Academician Shi's presentation was "Mitochondrial Dysfunction and Degenerative Diseases". She introduced the important physiological functions of mitochondria and their key role in the development of various diseases. Mitochondrial dysfunction may be the cause of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and muscular dystrophy. Mitochondria have their own genome, replication, and transcription system, encoding 13 components of the oxidative phosphorylation system. Like the nuclear genome, epigenetic modifications such as methylation are present in the mitochondrial rRNAs, which regulate the physiological functions of mitochondria. Mitochondrial TFB1M is a methyltransferase that specifically bis-methylates the adjacent bis-adenine on helix45 of mitochondrial 12S rRNA and plays an important role in the maintenance of mitochondrial homeostasis. However, the specific function of the catalytic mechanism of TFB1M in relation to the maintenance of mitochondrial homeostasis remains unclear.
By resolving the structures of the ternary complexes of human TFB1M with ribosomal 12S rRNA helix45 (h45) and SAM (S-adenosylmethionine), and the TFB1M-h45 binary complex, Academician Shi revealed the catalytic mechanism of TFB1M, and further revealed the effects of TFB1M on mitochondrial ATP production and oxidative phosphorylation system components by cell biology, indicating that this modification is essential for the assembly of mitochondrial ribosomes. In addition, Academician Shi also indicated her future research plan was to investigate the working mechanism of mitochondrial RNA granule in depth and contribute to the understanding of the physiopathological mechanism of mitochondria.
As a leading scientist in the field of chromatin structure and function, Research Fellow Li Guohong introduced the hierarchical and epigenetic regulation of chromatin with the topic of "Structural basis of the genome folding and human diseases". In his presentation, Li focused on the structure and dynamics of chromatin 30 nm fibers, especially the latest results based on cryo-electron microscopy and single molecule mechanics techniques. He found that the unit composed of four nucleosomes is a type of stable intermediate of 30 nm chromatin fibers, and that the chaperone protein FACT can reshape the dynamic structure of nucleosomes and even 30 nm fibers. Excitingly, Research Fellow Li Guohong also showed the HD results of H5 chromatin fibers. Then, using yeast and Drosophila as model organisms, he explained the association of 30nm fibers with cancer. Following that, at the level of omics, biochemistry and molecular biology, he presented the molecular mechanisms of 30nm fibers involved in epigenetic information reading and writing. Finally, Li Guohong discussed the function of chromatin 30nm fibers in human diseases, especially the abnormal function and inactivation of this structure in children with autism.
After the presentation, the two experts engaged in an in-depth discussion and exchange with the conference guests and online audience. Academician Shi Yunyu gave a detailed explanation on mitochondrial rRNA methylation affecting ribosome assembly and the communication between mitochondria and other cell organelles. Research Fellow Li Guohong answered questions on the elements of phase separation study of chromatin structure and the technical points of determining 30nm fiber morphology in cells. The whole forum was lively and interactive with a strong academic atmosphere.
Academician Shi Yunyu is a member of Chinese Academy of Sciences, a member of the World Academy of Sciences and a famous biophysicist and structural biologist. She started to engage in computerized molecular dynamics simulations of biological macromolecules in the 1980s, and was one of the pioneers in this field in China. After the mid-1990s, Shi was mainly engaged in the research of nuclear magnetic resonance spectroscopy of biomolecules, and was one of the forerunners of such research in China. Shi Yunyu led the establishment of the Key Laboratory of Structural Biology of the Chinese Academy of Sciences at the University of Science and Technology of China; led the research team of innovative talents of the National Natural Science Foundation of China, and trained a number of young discipline leaders working in these interdisciplinary fields of computational biology and structural biology. She was the first dean of the School of Life Sciences at the University of Science and Technology of China and made important contributions to the development of the School. From 2001 to 2010, Shi served as the director of the Steering Committee for Teaching Biological Sciences and Biological Engineering in Higher Education Institutions of the Ministry of Education, contributing to the promotion of talent training, teaching reform and curriculum construction in biology nationwide. In 2007, she was awarded the 3rd Teaching Master Award of Higher Education Institutions by the Ministry of Education. Her current research interests include the structural biological basis of gene expression regulation, molecular mechanism and functional significance, and relationship with aging and diseases.
Research Fellow Li Guohong is a research group leader of the Institute of Biophysics, Chinese Academy of Sciences, Deputy Director of National Laboratory of Biomacromolecules, a recipient of the National Outstanding Youth Fund, a winner of Tan Jiazhen Life Science Innovation Award and an International Scholar of HHMI. He is mainly engaged in the research of chromatin structure and epigenetic regulation, focusing on the molecular mechanism of chromatin advanced structure dynamics and its epigenetic regulation during the developmental differentiation of embryonic stem cells. His research also focuses on elucidation of the biological function and molecular mechanism of chromatin advanced structure dynamics regulation in cell fate determination. He has published more than 70 papers in prestigious international journals such as Science, Nature, Nature Cell Biology, Molecular Cell, Dev Cell, Nat Struct Mol Biol, Genes & Dev, Cell Res. and Cell Reports.