Help you stay away from "sweet troubles" glycobiology or unlock the key code of disease
Determine your blood type; a new "weapon" against viruses; the amount of information carried exceeds the sum of the amount of information carried by protein, nucleic acid and fat. It is a biological macromolecule-sugar that participates in every process of human birth, aging, sickness and death.
Sugars, proteins, nucleic acids, and lipids are the four biological macromolecules that constitute living organisms.
Sugar is involved in every life process of human development, birth, old age, sickness and death, and even human blood type is determined by sugar.
However, for a century, sugar research has been neglected. This year, the new crown virus triggered a global epidemic, which once again brought the importance of sugar to the surface.
"In the protracted war between humans and viruses, a new'weapon' is being developed and used. This is glycobiology." At the world's top scientists forum held recently, Lei Lei, the founder of glycobiology and the chief virus scientist of the British government Professor Mond Dwick said.
Carry more information than proteins and nucleic acids
"If biology research is a table, glycobiology is like a cup on the table. But in fact, the entire field of biology is related to sugar." In an interview with a reporter from Science and Technology Daily, a domestic glycobiologist and Shanghai Jiaotong University University professor Zhang Yan described the importance of glycobiology in this way.
The diversity of sugar structure makes it carry much more information than the sum of protein, nucleic acid and fat.
However, due to the complexity of sugar structure and the limitations of research methods, people's research and cognition of sugar lags far behind nucleic acids and proteins.
As Richard Cummings, the lead author of "Handbook of Glycomics," said, "The glycobiologists of the twentieth century are conducting research in hell." Zhang Yan wrote a preface for the Chinese version of this book in 2011 He wrote, "The glycobiologists of the 21st century are happy."
What kind of substance is sugar that scientists love and hate?
Professor Ye Xinshan, a well-known expert in sugar chemistry and deputy dean of the School of Pharmacy of Peking University, told a reporter from Science and Technology Daily that sugar is an indispensable substance for living organisms such as animals, plants and microorganisms, including monosaccharides, disaccharides, oligosaccharides and Polysaccharides.
The most common simple sugar in food is glucose, which provides the most basic energy of life.
Starch is a polysaccharide, which can be degraded into glucose.
"It is worth noting that more than 50% of the protein in human cells is covered with a'sugar coat', which exists and functions in the form of glycoproteins." Ye Xinshan emphasized that people are increasingly realizing that many problems in life sciences are not just The problem on the protein level is even more the problem on the glycoprotein level.
"Glycobiology is an indispensable branch of life sciences. Its research scope covers the research of gene level, protein level, cell biology and individual physiopathology. It is a multidisciplinary frontier subject." Zhang Yan explained. , Glycobiology research answers where and how the sugar chain (polysaccharide or glycan) of the human body is formed in the cell; reveals its structure at the molecular level, what kind of information it is combined with and what kind of information it contains; and how to use biology Function and other issues.
Ye Xinshan believes that protein and nucleic acid research has developed rapidly, and people’s understanding and understanding of life needs to be further advanced, and research on carbohydrates is needed.
"Most of the functions of sugar are still unknown mysteries. If this door is opened, humans will be more confident in the fight against disease," he said.
The shadow of "sugar" can be found behind most diseases
Sugar chains are closely related to human health and involve almost all types of diseases.
At present, people already know that sugar chains are closely related to infectious diseases, immune diseases, cardiovascular diseases, tumors, and neurodegenerative diseases.
The sugar chains currently concerned by biologists mainly refer to cell structure substances (chains) that are combined with proteins, lipids, etc., composed of 10 kinds of monosaccharide molecules such as glucose and galactose, such as glycoproteins and glycolipids. .
Zhang Yan introduced that in the past 200 years since sugar was discovered, there have been more than 1,000 types of sugar chains in the human body alone, and it is estimated that there are 10,000 to 20,000 types of sugar chains in nature.
Sugar chains present huge diversity of species structure and cell type specificity, which constitute the basis of their specific biological functions.
"But humans' knowledge of sugar chains is still very limited, which is a high ground and danger for diseases to challenge mankind."
Zhang Yan further elaborated that sugar chains determine human blood type, and there is a glycosyltransferase allele that determines ABO blood type on human chromosome 9.
Sugar chains are synthesized by glycosyltransferases. The differences in glycosyltransferase genes from parental alleles lead to differences in sugar chain structure. Therefore, ABO blood type is determined by the sugar chain structure; sugar chains give tumor cells, viruses and other immune functions, That is to say, sugar chains are involved in the process of tumor occurrence, development, and metastasis. The transmission mechanism of viruses such as new coronavirus, influenza virus, HIV, hepatitis B virus, and avian influenza virus is realized through the interaction of sugar and protein; blood tumor markers All substances are glycoproteins or sugar chains; sugar chains change the structure of lipoproteins and are related to cardiovascular diseases; lack of sugar chain synthesis causes various neurological diseases, such as Alzheimer’s disease and glycoprotein or glycolipid abnormalities; IgG sugars Changes in the chain (antibodies produced after human infection) are associated with autoimmune diseases such as rheumatoid arthritis.
In addition, diabetes is directly related to abnormal glucose metabolism in the body.
Diagnosis methods, drugs and vaccines based on sugar chains are being widely developed and used.
Ye Xinshan introduced 3 typical medical products that have been put on the market: Alpha-fetoprotein (AFP), a molecular marker for early diagnosis of liver cancer, is a glycoprotein, and the U.S. Food and Drug Administration (FDA) has approved it as a clinical diagnostic indicator. Its early diagnosis rate has reached 70%; the anti-influenza virus drug Tamiflu can inhibit the sialidase of the virus and achieve the effect of inhibiting the release of influenza virus, and has become the first-line drug for the treatment of influenza and avian influenza; Baitangping is a meal for controlling diabetes patients The first-line sugar drugs for post-blood sugar contain amylase inhibitors that can slow down the degradation of starch in the human gastrointestinal tract, thereby reducing blood sugar concentration.
Ye Xinshan said that sugar-based tumor vaccines are also under development.
“Many diseases are difficult to overcome. The problem is that the mechanism of action of sugar is not fully understood. The mechanism of action of glycoproteins on the surface of the new coronavirus is still a mystery. Solving this problem will provide a clearer path for vaccine and drug development. Similarly, the tumorigenesis mechanism is still shrouded in the fog, especially what role sugar plays in these processes, which leads to the lack of clear targets in the development and design of sugar-based tumor vaccines." Ye Xinshan said.
The technology for parsing "sugar" codes is constantly innovating
"There are two'dark clouds' in the sky of sugar science research. One is sugar synthesis and the other is sugar structure determination. The first dark cloud is dissipating, and scientists are gradually able to quickly synthesize the required sugar in the laboratory. The dispersal of the black cloud depends on the development of new sequencing analysis technology." Ye Xinshan often said to students.
The development of research methods and technology is an important driving force for the development of glycobiology.
Zhang Yan said: "Glycobiology research is carried out at the level of genes, proteins, cells and individuals. In daily research, students in our laboratory use gene editing, cell biology, proteomics, bioinformatics, etc. technology."
Focusing on the functions of sugars, Ye Xinshan summarizes the research techniques of sugar science into four categories: biological methods use gene editing technology to study sugar functions; chemical methods use sugar chain synthesis to verify sugar functions; chemical biological methods use probes and labels Ways to study the function of sugar chains; mass spectrometry to study the structure of complex sugar chains.
In addition to conventional biological research methods, Zhang Yan believes that the research of glycobiology requires chromatographic mass spectrometry technology, lectin chip, and sugar chain chip technology for sugar chain structure analysis; glycosyltransferase structure and sugar chain for synthesis of sugar chains. The three-dimensional structure analysis technology of complexes such as glycoproteins; the chemical enzymatic sugar engineering technology for the synthesis of sugar chains; the tracer imaging technology for cell sugar chain observation; and the establishment of international large databases related to sugar chain information.
With the help of abundant research methods, Ye Xinshan is full of confidence in the future of glycobiology.
"As scientists have more and more in-depth basic research on the functions of sugar and disease-related mechanisms, sugar-related drugs, vaccines, and diagnostic reagents will also enter a period of great development." He said.
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International glycobiology research is in full swing
Glycobiology research has received widespread attention and continued support in European countries, the United States and Japan.
"These international projects have a common feature, that is, the government takes the lead in vigorously carrying out basic sugar-related research, analyzing the function of sugar from the perspective of glycomics." Ye Xinshan said.
"The Japanese government has continuously invested in the field of sugar science in the past 30 years to support cutting-edge basic research and the development of new technologies based on sugar chains. It is expected that in the next 10 to 20 years, sugar science will make major breakthroughs in innovative drugs and medical diagnostics. Output." Zhang Yan said.
Ye Xinshan revealed that about 30 years ago, European and American genetic sciences were at the forefront of the world, and Japan was therefore ambitiously trying to take the lead in sugar research, so it provided great support for sugar scientific research.
Sugar science started in Europe. Zhang Yan said that the EU's sugar science development model has strong enlightenment for my country.
Under the EU ERU framework, the investment in sugar science research projects such as Glycoskin (2018-2023) is about 2 million euros.
In addition to national special support, the Nordic countries have also introduced policies to increase their enthusiasm for scientific research investment.
The reporter learned that most sugar science research in my country is a sub-project of other projects, and the support is less than that of nucleic acid and protein research.
Experts call for my country's urgent need to establish major national special projects for "carbohydrate biomacromolecules" with clear core goals, such as major protein projects and major infectious disease projects.