Observing the progress of life sciences from the development and transformation of instruments

The breakthrough of genetic technology has brought the development of life science into the era of knowledge explosion. Many new concepts and new technologies are dazzling. A few years ago people heard the terms "genome," "proteome," and "bioengineering." Scientists are talking about "life modules," "artificial circuit genes," and "nanoparticle intelligent missiles." What kind of route is going along? With this issue, the reporter recently entered several laboratories of the Institute of Biophysics of the Chinese Academy of Sciences.

"China Unicom" production efficiency

In the last few days of the last month of 2009, a gear-like gray metal circle was placed on the coffee table in the office of Yang Fuquan, a researcher at the Institute of Biophysics of the Chinese Academy of Sciences. This is a piece of his latest "work" that he designed and commissioned the company to complete. The factory has just opened it and waited for him to accept it.

“This is the core part of my newly developed countercurrent chromatograph—a new type of countercurrent chromatography column. I am going to use it for membrane protein enrichment and subcellular organelle isolation for membrane proteomics research.” The Scientific Times asked him to talk about the current development trend of biotechnology, he told reporters by the way.

"Is there such an instrument in the world?" the reporter asked.

"Not yet, but this still needs to be kept secret. I still show you something else."

In talking, Yang Fuquan took out an assembled "work" from the cabinet. "This is a capillary liquid chromatography-electrospray mass spectrometry interface platform, which is designed and processed at home through learning, digestion and absorption under the support of the Chinese Academy of Sciences instrument development and transformation project. This enables the instrument to adapt to a variety of complex proteins. Sample analysis. This preparation is to be installed on a new set of 2D-LC-MS systems."

According to Yang Fuquan, proteomics is one of the hot topics in life science research. Proteomics technology has developed rapidly, and competition in proteomics research is fierce. With a basic hardware device that allows the device to work efficiently, high-level work can be done. Among them, modern chromatographic separation technology and biological mass spectrometry technology constitute the main body of proteomics technology. Chromatography-mass spectrometry system connection directly affects the sensitivity and efficiency of the entire system. This interface platform is designed and processed for the deficiencies of commercial instruments. It is used in conjunction with a self-made capillary liquid chromatography column, which not only reduces the operating costs of the overall equipment, but also significantly increases the throughput, sensitivity and efficiency of the instrument system. .

Dr. Yang Fuquan returned from NIH National Heart, Lung, and Blood Institute in 2004 and currently serves as chief technical expert in mass spectrometry at the Institute of Biophysics, Chinese Academy of Sciences. He is mainly engaged in the research and application of new technologies and methods in proteomics. . The transformation of existing instruments and the development of new instruments and equipment in the field of life science research are among his important tasks.

Yang Fuquan introduced high-throughput analysis and identification of biological macromolecules such as peptides, proteins and nucleic acids through the combination of biological mass spectrometry and modern separation technologies such as two-dimensional electrophoresis, high performance liquid chromatography (HPLC) and capillary electrophoresis; In combination with fluorescence labeling technology, stable isotope labeling, and other technologies, high-throughput quantitative analysis of biological macromolecules has been realized, which has promoted the development of proteomics technology and promoted the application of proteomics technology in life sciences.

"After the renovation of the laboratory equipment and equipment, has the technical level been greatly improved?" the reporter asked.

Yang Fuquan did not directly answer the reporter's question. Instead, he opened an e-mail message to Shang Yongfeng, a newly elected academician of the Chinese Academy of Sciences and professor at Peking University. He wrote: “The students and students in my lab in the past two years The staff did a lot of mass spectrometry in your laboratory. These analyses played a big role in our research. The articles we published in 2009, including those in the magazines of Cell, PNAS and The Embo Journal, were all used. Your laboratory's mass spectrometry results, so I would like to express my sincere gratitude to you and the people involved in your lab. I have said on different occasions: Many domestic units have mass spectrometers, but they can really use them. I am very glad that you have this one in Beijing and have provided very good technical support for the research work of me and other laboratories. Our laboratory is mainly engaged in the research of the epigenetic mechanism of gene expression regulation and will surely continue to Need your support and help. I hope we can find a time to discuss the possibility of cooperative research.”

Yang Fuquan introduced that the current development trend of proteomics technology mainly includes three aspects: the development of high-resolution, high-quality accuracy and rapid mass spectrometry instruments; the development of highly efficient and selective sample enrichment technologies; Technologies such as modern separation technology and stable isotope labeling technology have been developed for the development of high-throughput quantitative proteomics technology. Because of the continuous application of proteomics technology in life sciences and protein science research, comprehensive analysis of dynamic changes in protein mass in cells, tissues, or organisms, or analysis of absolute quantities, has become an integral part of proteomics research. trend.

"Connect" speed

Liu Zhijie, a researcher at the Institute of Biophysics of the Chinese Academy of Sciences, explained the need for new equipment in the development of life sciences from another perspective. The researcher, who once participated in the work of the Southeastern Structural Genome Research Center, returned to China in 2006 and has been working to improve China's life science research equipment.

He said that 10 years ago, researchers would need about 1 to 2 years to analyze the three-dimensional structure of a protein. With the development of new technologies and new methods, as of the end of December 2009, the world has analyzed more than 70,000 protein molecules. Three-dimensional structure. These highly automated methods include high-throughput cloning, high-speed expression purification, automated protein crystallization, automated diffraction data collection, and structural analysis. If the researchers continue to adopt the old methods, the "Structural Genome Project" launched by the United States in 2000 could not be completed on time, and even one-tenth of them could not be done.

Currently, Liu Zhijie has established a high-throughput pipeline from the gene cloning to protein structure analysis at the protein research platform of the Institute of Biophysics of the Chinese Academy of Sciences. This first-class waterline consists of several modules, each of which strives to be automated. For example, the first module is automated cloning and small-scale soluble expression screening, using this module can automatically filter out soluble expressed proteins.

“If you use traditional methods, manual testing can only be done one by one, which is not only time consuming, laborious, but also error-prone. Now you can screen 96 target genes at a time and quickly understand which proteins are soluble under which conditions. Work that used to take months or years to complete can now be completed by a single person in a few days, he said.