Exploring the "previous life and life" of protein

Exploring the "previous life and life" of protein

The picture shows the nuclear magnetic resonance analysis system of the Protein Science Research (Shanghai) facility.

The dark clouds in life are always unexpected. An American girl who was in the flower season was suddenly told to have a very difficult cancer. Genetic testing showed that the incidence of cancer in her subtype was extremely low.

Only 2% of people with the same type of cancer have the same subtype as her. Fortunately, there is exactly one specific medicine for this subtype. After less than three months of treatment, she recovered.

Lei Ming, director of the National Protein Science Center and Shanghai (Funding), used this real case to vividly explain the future vision of precision medicine . But not all cancer patients are as lucky as the girl. What role does protein science play in the path of human access to precision medicine ? What is the role of the Protein Science Research (Shanghai) facility (hereinafter referred to as the “Shanghai Facility”), one of the major national science projects, in promoting protein science research?

In order to answer these questions, the author recently went to the National Protein Science Center·Shanghai (funding) to find out.

"Instrument cluster" that cannot be underestimated

Compared with the national science projects that have been in the past, the Shanghai facilities have not been able to create a powerful impact on the visual.

"We are mainly here a cluster of instruments for life science research with relatively small volume, so that at the beginning of the project, whether or not to include Shanghai facilities in large scientific projects is controversial." Lei Ming said.

Don't underestimate the "instrument cluster" here. Since the trial operation of the Shanghai facility in May 2014, more than 10 Nobel laureates and other internationally renowned experts who have come to visit have “liked” the advanced nature of the equipment.

Lei Ming recalled that more than a decade ago, China has achieved a number of internationally advanced research results in the field of protein science research, but it still lags behind the international advanced level. The lag in the construction of scientific research infrastructure is a key factor restricting the development of protein science.

Under the unremitting efforts of scientists, the National Science and Technology Infrastructure Project of the Protein Science Research Facility was approved in 2008 and became the first major scientific engineering project in the field of life sciences in China. The protein science research facilities are divided into two parts, Shanghai and Beijing. The Shanghai facility mainly focuses on the analysis of protein structure.

Focusing on the spatial scale of living organisms and the time scale of life processes, the Shanghai facility has built a large-scale protein preparation system, a protein crystal structure analysis system, a nuclear magnetic analysis system, an integrated electron microscope analysis system, a protein dynamic analysis system, and mass spectrometry. 9 major technical systems consisting of analytical system, composite laser microscopy imaging system, molecular imaging system and database and computational analysis system, with large-scale protein preparation, multi-scale structural analysis, multi-level dynamic research, modification and interaction analysis, and database and Calculate and analyze 5 major capabilities.

Steve Harrison is a mentor to Lei Ming when he was a Ph.D. student at Harvard University. After visiting the Shanghai facility, Steve felt very shocked and appreciated and envied the opportunity to participate in such a major project. In addition to envy, Lei Ming has been repeatedly asked: "What world-class jobs can you make on such an advanced research platform?"

A unique protein "smart factory"

Every protein is like a person and has its own temperament. It takes time to thoroughly study it.

In the 1960s and 1970s, there was a saying called "one protein, one career", meaning that a professor could only study a protein for a lifetime. "I mainly study telomeres. From the professors to the present, I have only analyzed the structure of dozens of proteins," Lei Ming said.

To find out the "temper" of a protein, the first step is to obtain a high-purity protein sample. If you want to see the "real body" of protein, you must break the cell. Once the cells are broken, 90% of the protein inside is destroyed at the same time, and the trace is difficult.

Saving after finding the target protein is also a problem. Protein is much more "squeaky" than the "pure" gene. The gene that records the genetic information is like a card that can be placed at will, without the worry of transsexuality. Proteins are different. Once environmental factors such as temperature, humidity, and light change, there is a risk of deterioration.

In traditional biological laboratories, researchers wearing white coats hold pipettes and adding reagents to bottles and jars filled with different liquids is a common scenario. In the large-scale protein preparation system of the Shanghai facility, this scene is being replaced by automated machine operations.

The central area of ​​the high-throughput cloning construction laboratory is an automated mechanical operating platform enclosed in a glass clean room. A computer with integrated software outside the console is responsible for “issuing orders”. After the scientific researcher starts the preset program, the white robot arm moves back and forth between the various automation instruments of the platform, and the 96-well plates are lightly placed on the designated plate. The positions of the various automated instruments can be performed by biological experiments such as adding liquid, shaking, centrifuging, and cleaning.

Traditionally hand-operated, one person has the most polyclonal dozen genes per day. The automated system in front of us can clone 960 genes a day, and the production efficiency is equivalent to a gene cloning enterprise of hundreds of people. "We hope to introduce the concept of automation into scientific research, and repeat labor to let the machine do it. Researchers can have more time to explore and think about real scientific problems." Deng Yu, director of the scaled protein preparation system, told the author.

The system of independent design and development of application facilities in Shanghai, like a “smart factory”, can complete a complete set of experimental operations from molecular biology to cell biology.

"The more integrated the automation equipment, the higher the chance of error. For a completely unfamiliar sample, our system can achieve 70% reliability, which is already a very good result." Thunder said.

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