Applied value of molecular biology. Applied Molecular Biology

Molecular biology has experienced a period of rapid development of its own research methods, which now distinguish it from biochemistry. These include, in particular, methods of genetic engineering, cloning, artificial expression and gene knockout. Since DNA is a material carrier of genetic information, molecular biology it became much closer to genetics, and molecular genetics was formed at the junction, which is both a branch of genetics and molecular biology. Just as molecular biology widely uses viruses as a research tool, in virology, methods of molecular biology are used to solve their problems. Computer technology is involved in the analysis of genetic information, and therefore new areas of molecular genetics have appeared, which are sometimes considered special disciplines: bioinformatics, genomics and proteomics.

History of development

This fundamental discovery was prepared by a long phase of research into the genetics and biochemistry of viruses and bacteria.

In 1928, Frederick Griffith showed for the first time that the extract of those killed by heating pathogenic bacteria can transmit pathogenicity to non-hazardous bacteria. The study of the transformation of bacteria further led to the purification of the pathogenic agent, which, contrary to expectations, turned out to be not a protein, but a nucleic acid. By itself, nucleic acid is not dangerous; it only carries genes that determine the pathogenicity and other properties of the microorganism.

In the 50s of the XX century, it was shown that bacteria have a primitive sexual process, they are able to exchange extrachromosomal DNA, plasmids. The discovery of plasmids, like transformation, formed the basis of plasmid technology widespread in molecular biology. Another important discovery for methodology was the discovery of bacterial viruses and bacteriophages at the beginning of the 20th century. Phages can also transfer genetic material from one bacterial cell to another. Infection of bacteria with phages leads to a change in the composition of bacterial RNA. If, without phages, the composition of RNA is similar to the composition of bacterial DNA, then after infection the RNA becomes more similar to the DNA of a bacteriophage. Thus, it was found that the structure of RNA is determined by the structure of DNA. In turn, the rate of protein synthesis in cells depends on the amount of RNA-protein complexes. So it was formulated central dogma of molecular biology: DNA ↔ RNA → protein.

The further development of molecular biology was accompanied both by the development of its methodology, in particular, by the invention of a method for determining the nucleotide sequence of DNA (W. Gilbert and F. Senger, Nobel Prize in Chemistry, 1980), and by new discoveries in the field of studies of the structure and functioning of genes (see. History of Genetics). By the beginning of the 21st century, data were obtained on the primary structure of all human DNA and a number of other organisms that are most important for medicine, agriculture and scientific research, which led to the emergence of several new directions in biology: genomics, bioinformatics, etc.

Literature

Singer M., Berg P. Genes and genomes. - Moscow, 1998.
Stent G., Calindar R. Molecular genetics. - Moscow, 1981.
Sambrook J., Fritsch E. F., Maniatis T. Molecular Cloning. - 1989.
Patrushev L. I. Gene expression. - M .: Nauka, 2000. - 000 p., Ill. ISBN 5-02-001890-2

Links

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See what "Molecular biology" is in other dictionaries:

MOLECULAR BIOLOGY - studies DOS. properties and manifestations of life on molecular level... The most important directions in M. b. are studies of the structurally functional organization of the genetic apparatus of cells and the mechanism of realization of hereditary information ... ... Biological encyclopedic dictionary

MOLECULAR BIOLOGY - explores the basic properties and manifestations of life at the molecular level. Finds out how and to what extent the growth and development of organisms, storage and transmission of hereditary information, transformation of energy in living cells, etc. phenomena are due to ... Big Encyclopedic Dictionary

MOLECULAR BIOLOGY Modern encyclopedia

MOLECULAR BIOLOGY - MOLECULAR BIOLOGY, the biological study of the structure and functioning of MOLECULES that make up living organisms. The main areas of study are physical and chemical properties proteins and NUCLEIC ACIDS such as DNA. see also… … Scientific and technical encyclopedic dictionary

molecular biology - section of biol., which explores the basic properties and manifestations of life at the molecular level. Finds out how and to what extent the growth and development of organisms, storage and transmission of hereditary information, transformation of energy in living cells and ... ... Microbiology Dictionary

molecular biology - - Topics of biotechnology EN molecular biology ... Technical translator's guide

Molecular biology - MOLECULAR BIOLOGY, explores the basic properties and manifestations of life at the molecular level. Finds out how and to what extent the growth and development of organisms, storage and transmission of hereditary information, transformation of energy in living cells and ... ... Illustrated Encyclopedic Dictionary

Molecular biology - a science that sets as its task the knowledge of the nature of the phenomena of vital activity by studying biological objects and systems at a level approaching the molecular level, and in some cases even reaching this limit. The ultimate goal in this ... ... Great Soviet Encyclopedia

MOLECULAR BIOLOGY - studies the phenomena of life at the level of macromolecules (hl.obr. proteins and nucleic acid) in cell structuresah (ribosomes, etc.), in viruses, as well as in cells. M.'s goal. establishing the role and mechanism of functioning of these macromolecules based on ... ... Chemical encyclopedia

molecular biology - explores the basic properties and manifestations of life at the molecular level. Finds out how and to what extent the growth and development of organisms, storage and transmission of hereditary information, transformation of energy in living cells and other phenomena ... ... encyclopedic Dictionary

Books

Molecular cell biology. Collection of problems, J. Wilson, T. Hunt. The book by American authors is an appendix to the 2nd edition of the textbook `Molecular biology of the cell` by B. Alberts, D. Bray, J. Lewis and others. Contains questions and tasks, the purpose of which is to deepen ...

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reference

Molecular biology grew out of biochemistry in April 1953. Its appearance is associated with the names of James Watson and Francis Crick, who discovered the structure of the DNA molecule. The discovery was made possible by research into genetics, bacteria and the biochemistry of viruses. The profession of a molecular biologist is not widespread, but today its role in modern society is very great. A large number of diseases, including those manifested at the genetic level, require scientists to search for solutions to this problem.

Description of activities

Viruses and bacteria constantly mutate, which means that medications stop helping a person and diseases become intractable. The task of molecular biology is to get ahead of this process and develop a new remedy for disease. Scientists work according to a well-established scheme: blocking the cause of the disease, eliminating the mechanisms of heredity and thereby alleviating the patient's condition. There are a number of centers, clinics and hospitals around the world where molecular biologists are developing new treatments to help patients.

Labor responsibilities

The responsibilities of a molecular biologist include studying processes within the cell (for example, changes in DNA during the development of tumors). Also, experts study the features of DNA, their effect on the whole organism and an individual cell. Such studies are carried out, for example, on the basis of PCR (polymerase chain reaction), which allows you to analyze the body for infections, hereditary diseases and determine biological relationship.

Features of career growth

The profession of a molecular biologist is quite promising in its field and today claims to be the first in the ranking of the medical professions of the future. By the way, a molecular biologist doesn't have to stay in this area all the time. If there is a desire to change his occupation, he can retrain as sales managers for laboratory equipment, start developing instruments for various research, or open his own business.

Molecular biology

a science that sets as its task the cognition of the nature of the phenomena of life by studying biological objects and systems at a level approaching the molecular level, and in some cases even reaching this limit. The ultimate goal in this case is to find out how and to what extent the characteristic manifestations of life, such as heredity, reproduction of one's own kind, protein biosynthesis, excitability, growth and development, storage and transmission of information, energy conversion, mobility, etc. , due to the structure, properties and interaction of molecules of biologically important substances, primarily two main classes of high molecular weight biopolymers (See Biopolymers) - proteins and nucleic acids. A distinctive feature of M. b. - study of the phenomena of life on inanimate objects or those that are inherent in the most primitive manifestations of life. These are biological formations from the cellular level and below: subcellular organelles, such as isolated cell nuclei, mitochondria, ribosomes, chromosomes, cell membranes; further - systems standing on the border of living and inanimate nature, - viruses, including bacteriophages, and ending with the molecules of the most important components of living matter - nucleic acids (See Nucleic acids) and proteins (See Proteins).

M. b. - a new area of \u200b\u200bnatural science, closely associated with long-established areas of research, which are covered by biochemistry (see Biochemistry), biophysics (see Biophysics), and bioorganic chemistry (see Bioorganic chemistry). The distinction here is possible only on the basis of taking into account the methods used and the fundamental nature of the approaches used.

The foundation on which M. b. Developed was laid by such sciences as genetics, biochemistry, physiology of elementary processes, and so on. According to the origins of his development, M. b. is inextricably linked with molecular genetics (See Molecular Genetics) , which continues to constitute an important part of M. b., although it has already formed to a large extent into an independent discipline. M.'s isolation. from biochemistry is dictated by the following considerations. The tasks of biochemistry are mainly limited to stating the participation of certain chemical substances with certain biological functions and processes and clarifying the nature of their transformations; the leading role belongs to information about the reactivity and the main features chemical structureexpressed by the usual chemical formula. Thus, in essence, attention is focused on the transformations affecting the main valence chemical bonds... Meanwhile, as was emphasized by L. Pauling , at biological systems and manifestations of vital activity, the main importance should be attributed not to the main valent bonds acting within one molecule, but to various types of bonds that cause intermolecular interactions (electrostatic, van der Waals, hydrogen bonds, etc.).

The end result of biochemical research can be presented in the form of one or another system chemical equations, usually completely exhausted by their image on a plane, that is, in two dimensions. Distinctive feature M. b. is its three-dimensionality. M.'s essence. M. Perutz sees it in interpreting biological functions in terms of molecular structure. We can say that if before, when studying biological objects, it was necessary to answer the question "what", that is, what substances are present, and to the question "where" - in what tissues and organs, then M. b. sets its task to get answers to the question "how", having learned the essence of the role and participation of the entire structure of the molecule, and to the questions "why" and "why", having clarified, on the one hand, the connections between the properties of the molecule (again, primarily proteins and nucleic acids) and the functions it performs and, on the other hand, the role of such individual functions in the general complex of manifestations of vital activity.

The decisive role is played by mutual arrangement atoms and their groupings in the general structure of the macromolecule, their spatial relationships. This applies to both individual, individual, components, and the general configuration of the molecule as a whole. It is as a result of the emergence of a strictly determined volumetric structure that biopolymer molecules acquire the properties due to which they are able to serve as the material basis of biological functions. This principle of approach to the study of living things is the most characteristic, typical feature of M. b.

Historical reference. I.P. Pavlov foresaw the enormous importance of research on biological problems at the molecular level , who spoke about the last step in the science of life - the physiology of a living molecule. The very term “M. b. " was first used in English. scientists W. Astbury in the application to studies concerning the elucidation of the relationship between the molecular structure and the physical and biological properties of fibrillar (fibrous) proteins, such as collagen, blood fibrin, or muscle contractile proteins. The term “M. b. " steel from the beginning of the 50s. 20th century

M.'s emergence. As an established science, it is customary to refer to 1953, when J. Watson and F. Crick in Cambridge (Great Britain) discovered the three-dimensional structure of deoxyribonucleic acid (see Deoxyribonucleic acid) (DNA). This allowed us to talk about how the details of this structure determine the biological functions of DNA as a material carrier of hereditary information. In principle, this role of DNA became known a little earlier (1944) as a result of the work of the American geneticist OT Avery and his colleagues (see Molecular Genetics), but it was not known to what extent this function depends on the molecular structure of DNA. This became possible only after new principles of X-ray structural analysis were developed in the laboratories of W. L. Bragg (see Bragg-Wolfe condition), J. Bernal and others, which ensured the use of this method for detailed knowledge of the spatial structure of protein macromolecules and nucleic acids.

Levels of molecular organization. In 1957 J. Kendrew established the three-dimensional structure of myoglobin a , and in subsequent years this was done by M. Perutz in relation to Hemoglobin a. The concepts of various levels of the spatial organization of macromolecules were formulated. The primary structure is the sequence of individual units (monomers) in the chain of the resulting polymer molecule. For proteins, the monomers are amino acids , for nucleic acids - Nucleotides. A linear, filamentous biopolymer molecule, as a result of the occurrence of hydrogen bonds, has the ability to fit in space in a certain way, for example, in the case of proteins, as L. Pauling showed, acquire the shape of a spiral. This is referred to as a secondary structure. A tertiary structure is said to be when a molecule with a secondary structure folds further in one way or another, filling three-dimensional space. Finally, molecules with a three-dimensional structure can interact, regularly located in space relative to each other and forming what is designated as a quaternary structure; its individual components are usually called subunits.

The most obvious example of how a three-dimensional molecular structure determines the biological functions of a molecule is DNA. It has the structure of a double helix: two threads running in a mutually opposite direction (antiparallel) are twisted around one another, forming a double helix with a mutually complementary arrangement of bases, i.e. so that opposite a certain base of one chain there is always such the base that best ensures the formation of hydrogen bonds: adepine (A) forms a pair with thymine (T), guanine (G) - with cytosine (C). This structure creates optimal conditions for the most important biological functions of DNA: the quantitative multiplication of hereditary information in the process of cell division while maintaining the qualitative invariability of this flow of genetic information. When a cell divides, the strands of the double helix of DNA, which serves as a template or template, are unwound and a complementary new strand is synthesized on each of them under the action of enzymes. As a result, from one parent DNA molecule, two daughter molecules completely identical to it are obtained (see Cell, Mitosis).

Likewise, in the case of hemoglobin, it turned out that its biological function - the ability to reversibly attach oxygen in the lungs and then give it to tissues - is closely related to the features of the three-dimensional structure of hemoglobin and its changes in the process of exercising its physiological role. During the binding and dissociation of O 2, spatial changes in the conformation of the hemoglobin molecule occur, leading to a change in the affinity of the iron atoms contained in it for oxygen. Changes in the size of the hemoglobin molecule, reminiscent of changes in the volume of the chest during breathing, made it possible to call hemoglobin "molecular lungs".

One of the most important features of living objects is their ability to finely regulate all manifestations of life. A major contribution of M. b. scientific discoveries should be considered the disclosure of a new, previously unknown regulatory mechanism, designated as an allosteric effect. It lies in the ability of substances of low molecular weight - the so-called. ligands - to modify the specific biological functions of macromolecules, primarily catalytically acting proteins - enzymes, hemoglobin, receptor proteins involved in the construction of biological membranes (see Biological membranes), in synaptic transmission (see Synapses), etc.

Three biotic streams.In the light of M.'s representations. the totality of the phenomena of life can be regarded as the result of a combination of three streams: the stream of matter, which finds its expression in the phenomena of metabolism, that is, assimilation and dissimilation; the flow of energy, which is the driving force for all manifestations of life; and the flow of information that permeates not only the whole variety of processes of development and existence of each organism, but also a continuous series of successive generations. It is precisely the idea of \u200b\u200bthe flow of information, introduced into the teaching of the living world by the development of M. b., Which leaves its specific, unique imprint on it.

Major advances in molecular biology. The swiftness, scope and depth of influence of M. b. success in understanding the fundamental problems of studying living nature is rightly compared, for example, with the influence of quantum theory on the development of atomic physics. Two internally related conditions defined this revolutionary impact. On the one hand, a decisive role was played by the discovery of the possibility of studying the most important manifestations of vital activity in the simplest conditions, approaching the type of chemical and physical experiments. On the other hand, as a consequence of this circumstance, there was a rapid involvement of a significant number of representatives of the exact sciences - physicists, chemists, crystallographers, and then mathematicians - in the development of biological problems. In their totality, these circumstances determined the unusually fast pace of development of medical science, the number and significance of its successes achieved in just two decades. Here is a far from complete list of these achievements: disclosure of the structure and mechanism of the biological function of DNA, all types of RNA and ribosomes (See Ribosomes) , disclosure of the genetic code (See genetic code) ; opening of reverse transcription (See Transcription) , i.e., DNA synthesis on an RNA template; study of the mechanisms of the functioning of respiratory pigments; the discovery of the three-dimensional structure and its functional role in the action of enzymes (See Enzymes) , the principle of matrix synthesis and mechanisms of protein biosynthesis; disclosure of the structure of viruses (see. Viruses) and mechanisms of their replication, primary and, partially, the spatial structure of antibodies; isolation of individual genes , chemical and then biological (enzymatic) synthesis of a gene, including a human one, outside the cell (in vitro); transfer of genes from one organism to another, including human cells; the rapidly advancing deciphering of the chemical structure of an increasing number of individual proteins, mainly enzymes, as well as nucleic acids; detection of the phenomena of "self-assembly" of some biological objects of increasing complexity, starting from nucleic acid molecules and moving to multicomponent enzymes, viruses, ribosomes, etc .; elucidation of allosteric and other basic principles of regulation of biological functions and processes.

Reductionism and integration. M. b. is the final stage of the direction in the study of living objects, which is designated as "reductionism", ie, the desire to reduce complex vital functions to phenomena occurring at the level of molecules and therefore accessible to study by methods of physics and chemistry. Achieved by M. b. successes demonstrate the effectiveness of this approach. At the same time, it should be borne in mind that in natural conditions in a cell, tissue, organ and the whole organism, we are dealing with systems of an increasing degree of complexity. Such systems are formed from components of more low level by means of their natural integration into integrity, acquiring a structural and functional organization and possessing new properties. Therefore, as the knowledge about the patterns available for disclosure at the molecular and adjacent levels becomes more detailed, before M. b. the tasks of understanding the mechanisms of integration as a line of further development in the study of the phenomena of life arise. The starting point here is the study of the forces of intermolecular interactions - hydrogen bonds, van der Waals, electrostatic forces, etc. By their totality and spatial arrangement, they form what can be called "integrative information". It should be considered as one of the main parts of the already mentioned information flow. In the area of \u200b\u200bM. b. examples of integration are the phenomena of self-assembly of complex formations from a mixture of their constituent parts. These include, for example, the formation of multicomponent proteins from their subunits, the formation of viruses from their constituent parts - proteins and nucleic acid, restoration of the original structure of ribosomes after the separation of their protein and nucleic components, etc. The study of these phenomena is directly related to the knowledge of the main phenomena " recognition "of biopolymer molecules. The point is to find out what combinations of amino acids - in protein or nucleotide molecules - in nucleic acids interact with each other during the processes of association of individual molecules with the formation of complexes of a strictly specific, predetermined composition and structure. This includes the formation of complex proteins from their subunits; further, selective interaction between nucleic acid molecules, for example, transport and template (in this case, the disclosure of the genetic code significantly expanded our information); finally, it is the formation of many types of structures (for example, ribosomes, viruses, chromosomes), in which both proteins and nucleic acids are involved. The disclosure of the corresponding regularities, the cognition of the "language" underlying these interactions, constitutes one of the most important areas of mathematical biology, still awaiting its development. This area is considered as one of the fundamental problems for the entire biosphere.

The problems of molecular biology. Along with the indicated important tasks of M. b. (knowledge of the patterns of "recognition", self-assembly and integration) an urgent direction of scientific search for the near future is the development of methods that allow decoding the structure, and then the three-dimensional, spatial organization of high molecular weight nucleic acids. At this time, this has been achieved in relation to the general plan of the three-dimensional structure of DNA (double helix), but without an exact knowledge of its primary structure. Rapid development gains analytical methods allow us to confidently wait for the achievement of these goals in the coming years. Here, of course, the main contributions come from representatives of related sciences, primarily physics and chemistry. All the most important methods, the use of which ensured the emergence and success of medical science, were proposed and developed by physicists (ultracentrifugation, X-ray structural analysis, electron microscopy, nuclear magnetic resonance, etc.). Almost all new physical experimental approaches (for example, the use of computers, synchrotron or bremsstrahlung radiation, laser technology, etc.) open up new possibilities for in-depth study problems M. b. Among the most important tasks of a practical nature, the answer to which is expected from M. b., In the first place is the problem of the molecular foundations of malignant growth, then - ways of preventing, and perhaps overcoming, hereditary diseases - "molecular diseases" (See. Molecular diseases ). Elucidation of the molecular basis of biological catalysis, that is, the action of enzymes, will be of great importance. Among the most important modern directions of M. b. should include the desire to decipher the molecular mechanisms of action of hormones (See Hormones) , toxic and medicinal substances, as well as to find out the details of the molecular structure and functioning of such cellular structures as biological membranesparticipating in the regulation of the processes of penetration and transport of substances. More distant goals of M. b. - cognition of the nature of nervous processes, memory mechanisms (See Memory), etc. One of the important emerging sections of M. b. - the so-called. genetic engineering, which sets as its task the purposeful operation of the genetic apparatus (genome) of living organisms, starting with microbes and lower (unicellular) ones and ending with humans (in the latter case, primarily for the purpose of radical treatment of hereditary diseases (see Hereditary diseases) and correction of genetic defects ). More extensive interventions into the genetic basis of a person can be discussed only in a more or less distant future, since in this case serious obstacles of both a technical and fundamental nature arise. With regard to microbes, plants, and possibly agricultural. For animals, such prospects are very promising (for example, obtaining varieties of cultivated plants that have an apparatus for fixing nitrogen from the air and do not need fertilizers). They build on the successes already achieved: isolating and synthesizing genes, transferring genes from one organism to another, using popular crops cells as producers of economic or medical important substances.

Organization of research in molecular biology. M.'s rapid development. entailed the emergence of a large number of specialized research centers. Their number is growing rapidly. The largest: in Great Britain - the Laboratory of Molecular Biology in Cambridge, the Royal Institute in London; in France - the institutes of molecular biology in Paris, Marseille, Strasbourg, the Pasteur Institute; in the USA - departments of M. b. at universities and institutes in Boston (Harvard University, Massachusetts Institute of Technology), San Francisco (Berkeley), Los Angeles (California Institute of Technology), New York (Rockefeller University), health institutes in Bethesda, etc .; in Germany - the Max Planck Institutes, universities in Göttingen and Munich; in Sweden - the Karolinska Institute in Stockholm; in the German Democratic Republic - the Central Institute of Molecular Biology in Berlin, institutes in Jena and Halle; in Hungary - the Biological Center in Szeged. In the USSR, the first specialized institute of M. b. was created in Moscow in 1957 in the system of the USSR Academy of Sciences (see. ); then the Institute of Bioorganic Chemistry of the Academy of Sciences of the USSR in Moscow, the Institute of Protein in Pushchino, the Biological Department at the Institute of Atomic Energy (Moscow), departments of M. b. at the institutes of the Siberian Branch of the Academy of Sciences in Novosibirsk, the Interfaculty Laboratory of Bioorganic Chemistry of Moscow State University, the sector (then the Institute) of Molecular Biology and Genetics of the Academy of Sciences of the Ukrainian SSR in Kiev; significant work on M. b. is conducted at the Institute of Macromolecular Compounds in Leningrad, in a number of departments and laboratories of the USSR Academy of Sciences and other departments.

Organizations of a broader scale have sprung up along with individual research centers. AT Western Europe the European organization for M. arose. (EMBO), in which more than 10 countries participate. In the USSR, at the Institute of Molecular Biology, a scientific council for molecular biology was created in 1966, which is a coordinating and organizing center in this area of \u200b\u200bknowledge. He has published an extensive series of monographs on the most important sections of medical science, regularly organizes "winter schools" on medical science, holds conferences and symposia on topical problems of medical science. In the future, scientific advice on M. b. were created at the USSR Academy of Medical Sciences and many republican Academies of Sciences. Since 1966 the journal Molecular Biology has been published (6 issues per year).

In a relatively short period of time in the USSR, a significant detachment of researchers in the field of medical science has grown; these are scientists of the older generation who have partially switched their interests from other areas; in the main, they are numerous young researchers. Among the leading scientists who took an active part in the formation and development of M. b. in the USSR, you can name such as A. A. Baev, A. N. Belozersky, A. E. Braunshtein, Yu. A. Ovchinnikov, A. S. Spirin, M. M. Shemyakin, V. A. Engelgardt. M.'s new achievements. and molecular genetics will be promoted by the decree of the Central Committee of the CPSU and the Council of Ministers of the USSR (May 1974) "On measures to accelerate the development of molecular biology and molecular genetics and the use of their achievements in the national economy."

Lit .: Wagner R., Mitchell G., Genetics and metabolism, trans. from English., M., 1958; Saint-Gyorgy and A., Bioenergy, trans. from English., M., 1960; Anfinsen K., Molecular foundations of evolution, trans. from English., M., 1962; Stanley W., Valens E., Viruses and the Nature of Life, trans. from English, M., 1963; Molecular Genetics, trans. from. English, part 1, M., 1964; Volkenshtein M.V., Molecules and Life. Introduction to molecular biophysics, M., 1965; F. Gaurowitz, Chemistry and function of proteins, trans. from English, M., 1965; Bresler SE, Introduction to molecular biology, 3rd ed., M. - L., 1973; Ingram V., Biosynthesis of macromolecules, trans. from English, M., 1966; Engelhardt VA, Molecular biology, in the book: Development of biology in the USSR, M., 1967; Introduction to Molecular Biology, trans. from English., M., 1967; Watson J., Molecular Biology of the Gene, trans. from English, M., 1967; Finean J., Biological ultrastructures, trans. from English., M., 1970; J. Bendall, Muscles, Molecules and Movement, trans. from English., M., 1970; Ichas M., Biological code, trans. from English, M., 1971; Molecular biology of viruses, M., 1971; Molecular bases of protein biosynthesis, M., 1971; Bernhard S., Structure and function of enzymes, trans. from English, M., 1971; Spirin A.S., Gavrilova L.P., Ribosoma, 2nd ed., M., 1971; Frenkel-Konrat H., Chemistry and Biology of Viruses, trans. from English., M., 1972; Smith K., Hanewalt F., Molecular Photobiology. Processes of inactivation and restoration, trans. from English., M., 1972; Harris G., Fundamentals of human biochemical genetics, trans. from English, M., 1973.

V.A.Engelgardt.

Great Soviet Encyclopedia. - M .: Soviet encyclopedia. 1969-1978 .

Molecular biology, a science that sets as its task the cognition of the nature of the phenomena of life by studying biological objects and systems at a level approaching the molecular level, and in some cases even reaching this limit. The ultimate goal in this case is to find out how and to what extent the characteristic manifestations of life, such as heredity, reproduction of one's own kind, protein biosynthesis, excitability, growth and development, storage and transmission of information, energy conversion, mobility, etc. , are due to the structure, properties and interaction of molecules of biologically important substances, primarily two main classes of high molecular weight biopolymers - proteins and nucleic acids. A distinctive feature of M. b. - study of the phenomena of life on inanimate objects or those that are inherent in the most primitive manifestations of life. These are biological formations from the cellular level and below: subcellular organelles, such as isolated cell nuclei, mitochondria, ribosomes, chromosomes, cell membranes; further - systems that stand on the border of living and inanimate nature - viruses, including bacteriophages, and ending with the molecules of the most important components of living matter - nucleic acids and proteins.

A distinctive feature of M. b. is its three-dimensionality. M.'s essence. M. Perutz sees it in interpreting biological functions in terms of molecular structure. M. b. sets its task to get answers to the question "how", having learned the essence of the role and participation of the entire structure of the molecule, and to the questions "why" and "why", having clarified, on the one hand, the relationship between the properties of the molecule (again, primarily proteins and nucleic acids) and the functions it performs and, on the other hand, the role of such individual functions in the general complex of manifestations of vital activity.

Major advances in molecular biology. Here is a far from complete list of these achievements: disclosure of the structure and mechanism of the biological function of DNA, all types of RNA and ribosomes, disclosure of the genetic code; discovery of reverse transcription, i.e. DNA synthesis on an RNA template; study of the mechanisms of the functioning of respiratory pigments; the discovery of the three-dimensional structure and its functional role in the action of enzymes, the principle of matrix synthesis and the mechanisms of protein biosynthesis; disclosure of the structure of viruses and mechanisms of their replication, primary and, partially, the spatial structure of antibodies; isolation of individual genes, chemical and then biological (enzymatic) synthesis of a gene, including human, outside the cell (in vitro); transfer of genes from one organism to another, including into human cells; the rapidly advancing deciphering of the chemical structure of an increasing number of individual proteins, mainly enzymes, as well as nucleic acids; detection of the phenomena of "self-assembly" of some biological objects of increasing complexity, starting from nucleic acid molecules and moving to multicomponent enzymes, viruses, ribosomes, etc .; elucidation of allosteric and other basic principles of regulation of biological functions and processes.

The problems of molecular biology. Along with the indicated important tasks of M. b. (cognition of the patterns of "recognition", self-assembly and integration) an urgent direction of scientific search for the near future is the development of methods that make it possible to decipher the structure, and then the three-dimensional, spatial organization of high molecular weight nucleic acids. All the most important methods, the use of which ensured the emergence and success of medical science, were proposed and developed by physicists (ultracentrifugation, X-ray structural analysis, electron microscopy, nuclear magnetic resonance, etc.). Almost all new physical experimental approaches (for example, the use of computers, synchrotron, or bremsstrahlung, radiation, laser technology, etc.) open up new possibilities for an in-depth study of the problems of medical science. Among the most important tasks of a practical nature, the answer to which is expected from M. b., In the first place is the problem of the molecular basis of malignant growth, then - ways of preventing, and perhaps overcoming, hereditary diseases - "molecular diseases". Elucidation of the molecular basis of biological catalysis, that is, the action of enzymes, will be of great importance. Among the most important modern directions of M. b. should include the desire to decipher the molecular mechanisms of action of hormones, toxic and medicinal substances, as well as to elucidate the details of the molecular structure and functioning of such cellular structures as biological membranes involved in the regulation of the processes of penetration and transport of substances. More distant goals of M. b. - cognition of the nature of nervous processes, memory mechanisms, etc. One of the important emerging sections of M. b. - the so-called. genetic engineering, which sets as its task the purposeful operation of the genetic apparatus (genome) of living organisms, starting with microbes and lower (unicellular) ones and ending with humans (in the latter case, primarily for the purpose of radical treatment of hereditary diseases and correction of genetic defects).

The most important areas of MB:

- Molecular genetics - the study of the structural and functional organization of the genetic apparatus of the cell and the mechanism of realization of hereditary information

- Molecular Virology - the study of the molecular mechanisms of the interaction of viruses with cells

- Molecular immunology - the study of the patterns of the body's immune reactions

- Molecular developmental biology - the study of the appearance of different quality of cells during individual development organisms and cell specialization

The main objects of research: Viruses (including bacteriophages), Cells and subcellular structures, Macromolecules, Multicellular organisms.

Comics for the competition "bio / mol / text": Today, the molecular biologist Test tube will guide you through the world of amazing science - molecular biology! We will begin with a historical excursion through the stages of its development and describe the main discoveries and experiments since 1933. And we will also clearly tell about the main methods of molecular biology, which made it possible to manipulate genes, change and isolate them. The emergence of these methods served as a strong impetus for the development of molecular biology. Let us also recall the role of biotechnology and touch upon one of the most popular topics in this area - genome editing using CRISPR / Cas systems.

General sponsor of the competition and partner of the Skoltech nomination -.

The sponsor of the competition is the Diaem company: the largest supplier of equipment, reagents and consumables for biological research and production.

The company was the sponsor of the Audience Award.

"Book" sponsor of the competition - "Alpina non-fiction"

1. Introduction. The essence of molecular biology

Studies the basics of the life of organisms at the level of macromolecules. The goal of molecular biology is to establish the role and mechanisms of functioning of these macromolecules based on knowledge about their structures and properties.

Historically, molecular biology was formed in the course of the development of areas of biochemistry that study nucleic acids and proteins. While biochemistry investigates metabolism, the chemical composition of living cells, organisms and the chemical processes carried out in them, molecular biology focuses on the study of the mechanisms of transmission, reproduction and storage of genetic information.

And the object of study of molecular biology is the nucleic acids themselves - deoxyribonucleic (DNA), ribonucleic (RNA) - and proteins, as well as their macromolecular complexes - chromosomes, ribosomes, multienzyme systems that ensure the biosynthesis of proteins and nucleic acids. Molecular biology also borders on research objects and overlaps with molecular genetics, virology, biochemistry and a number of other related biological sciences.

2. Historical excursion through the stages of development of molecular biology

As a separate branch of biochemistry, molecular biology began to develop in the 30s of the last century. Even then, it became necessary to understand the phenomenon of life at the molecular level in order to study the processes of transmission and storage of genetic information. It was at that time that the task of molecular biology was established in the study of the properties, structure and interaction of proteins and nucleic acids.

For the first time the term "molecular biology" was used in 1933 year William Astbury in the course of research on fibrillar proteins (collagen, blood fibrin, muscle contractile proteins). Astbury studied the relationship between molecular structure and biological, physical characteristics of these proteins. At the beginning of the emergence of molecular biology, RNA was considered a component only of plants and fungi, and DNA - only animals. And in 1935 the discovery of DNA in peas by Andrey Belozersky led to the establishment of the fact that DNA is contained in every living cell.

AT 1940 year, a colossal achievement was the establishment of a causal relationship between genes and proteins by George Beadle and Edward Tatem. The scientists' hypothesis "One gene - one enzyme" formed the basis for the concept that the specific structure of a protein is regulated by genes. It is believed that genetic information is encoded by a special sequence of nucleotides in DNA that regulates the primary structure of proteins. Later it was proved that many proteins have a quaternary structure. Various peptide chains are involved in the formation of such structures. Based on this, the provision on the relationship between the gene and the enzyme has been somewhat modified, and now sounds like "One gene - one polypeptide."

AT 1944 year, American biologist Oswald Avery and colleagues (Colin McLeod and McLean McCarthy) proved that the substance that causes the transformation of bacteria is DNA, not proteins. The experiment served as proof of the role of DNA in the transmission of hereditary information, crossing out outdated knowledge about the protein nature of genes.

In the early 1950s, Frederic Sanger showed that a protein chain is a unique sequence of amino acid residues. AT 1951 and 1952 years the scientist determined the complete sequence of two polypeptide chains - bovine insulin AT (30 amino acid residues) and AND (21 amino acid residues), respectively.

At about the same time, in 1951–1953 years, Erwin Chargaff formulated the rules for the ratio of nitrogenous bases in DNA. According to the rule, regardless of the species differences of living organisms in their DNA, the amount of adenine (A) is equal to the amount of thymine (T), and the amount of guanine (G) is equal to the amount of cytosine (C).

AT 1953 the genetic role of DNA has been proven. James Watson and Francis Crick, on the basis of an X-ray of DNA obtained by Rosalind Franklin and Maurice Wilkins, established the spatial structure of DNA and put forward a later confirmed assumption about the mechanism of its replication (doubling), which is the basis of heredity.

1958 year - the formation of the central dogma of molecular biology by Francis Crick: the transfer of genetic information goes in the direction of DNA → RNA → protein.

The essence of the dogma is that cells have a certain directed flow of information from DNA, which, in turn, is the original genetic text, consisting of four letters: A, T, G and C. It is written in the double helix of DNA in the form sequences of these letters - nucleotides.

This text is transcribed. And the process itself is called transcription... In the course of this process, RNA is synthesized, which is identical to the genetic text, but with a difference: instead of T in RNA, there is U (uracil).

This RNA is called messenger RNA (mRNA), or matrix (mRNA). Broadcast mRNA is carried out using the genetic code in the form of triplet nucleotide sequences. During this process, the text of DNA and RNA nucleic acids is translated from a four-letter text into a twenty-letter amino acid text.

There are only twenty natural amino acids, and there are four letters in the text of nucleic acids. Because of this, there is a translation from the four-letter alphabet to the twenty-letter alphabet by means of a genetic code in which an amino acid corresponds to every three nucleotides. So you can make as many as 64 three-letter combinations of four letters, while there are 20 amino acids. From this it follows that the genetic code must necessarily have the property of degeneracy. However, at that time the genetic code was not known, moreover, they did not even begin to decipher it, but Crick had already formulated his central dogma.

Nevertheless, there was a belief that the code should exist. By that time, this code had been proven to have tripletness. This means that specifically three letters in nucleic acids ( codons) correspond to any amino acid. There are 64 of these codons, they encode 20 amino acids. This means that several codons correspond to each amino acid at once.

Thus, we can conclude that the central dogma is a postulate that a directed flow of information occurs in the cell: DNA → RNA → protein. Crick emphasized the main content of the central dogma: the reverse flow of information cannot occur, the protein is not able to change genetic information.

This is the main meaning of the central dogma: a protein is not able to change and transform information into DNA (or RNA), the flow always goes only in one direction.

Some time after this, a new enzyme was discovered, which was not known at the time of the formulation of the central dogma, - reverse transcriptasewhich synthesizes DNA from RNA. The enzyme was discovered in viruses in which genetic information is encoded in RNA, not DNA. These viruses are called retroviruses. They have a viral capsule with RNA and a special enzyme enclosed in it. The enzyme is reverse transcriptase, which synthesizes DNA according to the template of this viral RNA, and this DNA then serves as the genetic material for the further development of the virus in the cell.

Of course, this discovery caused great shock and a lot of controversy among molecular biologists, since it was believed that, based on the central dogma, this could not be. However, Crick immediately explained that he never said it was impossible. He only said that there can never be a flow of information from protein to nucleic acids, and already inside nucleic acids of any kind processes are quite possible: DNA synthesis into DNA, DNA into RNA, RNA into DNA and RNA into RNA.

After the formulation of the central dogma, a number of questions remained: how does the alphabet of four nucleotides that make up DNA (or RNA) encode the 20-letter alphabet of amino acids that make up proteins? What is the essence of the genetic code?

The first ideas about the existence of the genetic code were formulated by Alexander Downs ( 1952 g.) and Georgy Gamov ( 1954 g.). Scientists have shown that the sequence of nucleotides must include at least three links. It was later proved that such a sequence consists of three nucleotides, called codon (triplet). Nevertheless, the question of which nucleotides are responsible for the inclusion of which amino acid in a protein molecule remained open until 1961.

And in 1961 Marshall Nirenberg and Heinrich Mattei used the system to broadcast in vitro... An oligonucleotide was taken as a template. It consisted only of uracil residues, and the peptide synthesized from it included only the amino acid phenylalanine. Thus, for the first time, the codon value was established: the UUU codon encodes phenylalanine. After them, the Har Quran found out that the nucleotide sequence UCUCUCUCUCUC encodes a set of amino acids serine-leucine-serine-leucine. By and large, thanks to the work of Nirenberg and the Koran, to 1965 year the genetic code was completely unraveled. It turned out that each triplet encodes a specific amino acid. And the order of codons determines the order of amino acids in a protein.

The main principles of the functioning of proteins and nucleic acids were formulated by the beginning of the 70s. It was recorded that the synthesis of proteins and nucleic acids is carried out by a matrix mechanism. The template molecule carries encoded information about the sequence of amino acids or nucleotides. During replication or transcription, the template is DNA; during translation and reverse transcription, it is mRNA.

Thus, the prerequisites were created for the formation of directions in molecular biology, including genetic engineering. And in 1972, Paul Berg and his colleagues developed a molecular cloning technology. Scientists get the first recombinant DNA in vitro... These outstanding discoveries formed the basis for a new direction in molecular biology, and 1972 the year since then is considered the birth date of genetic engineering.

3. Methods of molecular biology

Colossal advances in the study of nucleic acids, the structure of DNA and protein biosynthesis have led to the creation of a number of methods that have great importance in medicine, agriculture and science in general.

After studying the genetic code and the basic principles of storing, transferring and realizing hereditary information, special methods became necessary for the further development of molecular biology. These methods would allow genes to be manipulated, modified and isolated.

The emergence of such methods took place in the 1970s and 1980s. This gave a huge impetus to the development of molecular biology. First of all, these methods are directly related to the production of genes and their introduction into the cells of other organisms, as well as the ability to determine the sequence of nucleotides in genes.

3.1. DNA electrophoresis

DNA electrophoresis is the basic method for working with DNA. DNA electrophoresis is used along with almost all other methods to isolate the desired molecules and further analyze the results. The very method of gel electrophoresis is used to separate DNA fragments by length.

Before or after electrophoresis, the gel is treated with dyes that can bind to DNA. The dyes fluoresce in ultraviolet light, resulting in a pattern of bands in the gel. To determine the lengths of DNA fragments, they can be compared with by markers - sets of fragments of standard lengths, which are applied to the same gel.

Fluorescent proteins

When studying eukaryotic organisms, it is handy to use fluorescent proteins as marker genes. Gene of the first green fluorescent protein ( green fluorescent protein, GFP) isolated from jellyfish Aqeuorea victoria, after which they were introduced into various organisms. Then the genes of fluorescent proteins of other colors were isolated: blue, yellow, red. To obtain proteins with properties of interest, such genes were artificially modified.

In general, the most important tools for working with a DNA molecule are enzymes that carry out a number of DNA transformations in cells: DNA polymerase, DNA ligases and restriction enzymes (restriction endonucleases).

Transgenesis

Transgenesis called the transfer of genes from one organism to another. And such organisms are called transgenic.

Recombinant protein preparations are just obtained by transferring genes into the cells of microorganisms. Basically, these protein preparations are interferons, insulin, some protein hormones, and proteins for the production of a number of vaccines.

In other cases, cell cultures of eukaryotes or transgenic animals are used, mostly livestock, which secretes the required proteins into milk. In this way, antibodies, clotting factors and other proteins are obtained. The method of transgenesis is used to obtain crop plants resistant to pests and herbicides, and with the help of transgenic microorganisms, wastewater is purified.

In addition to all of the above, transgenic technologies are irreplaceable in scientific research, because the development of biology is faster with the use of methods of modification and gene transfer.

Restriction enzymes

The sequences recognized by restriction endonucleases are symmetrical, therefore, all kinds of breaks can occur either in the middle of such a sequence, or with a shift in one or both strands of the DNA molecule.

When any DNA is digested with a restriction enzyme, the sequences at the ends of the fragments will be the same. They will be able to connect again because they have complementary sites.

You can get a single molecule by stitching these sequences using DNA ligases... Due to this, it is possible to combine fragments of two different DNAs and obtain recombinant DNA.

3.2. PCR

The method is based on the ability of DNA polymerases to complete the second DNA strand along the complementary strand in the same way as in the process of DNA replication in a cell.

3.3. DNA sequencing

The rapid development of the sequencing method makes it possible to effectively determine the characteristics of the studied organism at the level of its genome. The main advantage of such genomic and post-genomic technologies is to increase the possibilities of research and study of the genetic nature of human diseases in order to take the necessary measures in advance and avoid diseases.

Through large-scale research, it is possible to obtain the necessary data on the various genetic characteristics of different groups of people, thereby developing medical methods. Because of this, the identification of genetic susceptibility to various diseases is very popular today.

Such methods are widely used almost all over the world, including in Russia. Due to scientific progress, such methods are being introduced into medical research and medical practice in general.

4. Biotechnology

Biotechnology - a discipline that studies the possibilities of using living organisms or their systems for solving technological problems, as well as creating living organisms with the desired properties by means of genetic engineering. Biotechnology applies methods of chemistry, microbiology, biochemistry and, of course, molecular biology.

The main directions of the development of biotechnology (the principles of biotechnological processes are introduced into the production of all industries):

Creation and production of new types of food and animal feed.
Obtaining and studying new strains of microorganisms.
Breeding new varieties of plants, as well as creating means for protecting plants from diseases and pests.
Application of biotechnology methods for environmental needs. Such biotechnology methods are used for waste recycling, cleaning wastewater, exhaust air and soil sanitation.
Production of vitamins, hormones, enzymes, serums for the needs of medicine. Biotechnologists are developing improved drugs that were previously considered incurable.

Genetic engineering is a major advance in biotechnology.

Genetic Engineering - a set of technologies and methods for producing recombinant RNA and DNA molecules, isolating individual genes from cells, manipulating genes and introducing them into other organisms (bacteria, yeast, mammals). Such organisms are capable of producing end products with the desired, altered properties.

Genetic engineering methods are aimed at constructing new, previously non-existent combinations of genes in nature.

Speaking about the achievements of genetic engineering, it is impossible not to touch upon the topic of cloning. Cloning is one of the methods of biotechnology used to obtain identical descendants of different organisms through asexual reproduction.

In other words, cloning can be thought of as the process of creating genetically identical copies of an organism or cell. And the cloned organisms are similar or completely identical not only in appearance, but also in genetic content.

The notorious Dolly the sheep became the first cloned mammal in 1966. It was obtained by transplanting the nucleus of a somatic cell into the cytoplasm of the egg. Dolly was a genetic copy of a nuclear donor sheep. Under natural conditions, an individual is formed from one fertilized egg, having received half of the genetic material from two parents. However, during cloning, the genetic material was taken from the cell of one individual. First, the nucleus was removed from the zygote, in which the DNA itself is located. After that, the nucleus was removed from the cell of an adult sheep and implanted into that zygote devoid of a nucleus, and then it was transplanted into the uterus of an adult and provided an opportunity for growth and development.

However, not all cloning attempts have been successful. In parallel with Dolly's cloning, a DNA replacement experiment was performed on 273 other eggs. But only in one case was a living adult animal able to fully develop and grow. After Dolly, scientists tried to clone other types of mammals.

One of the types of genetic engineering is genome editing.

The CRISPR / Cas tool is based on an element of the immune defense system of bacteria, which scientists have adapted to introduce any changes in the DNA of animals or plants.

CRISPR / Cas is one of the biotechnological methods for manipulating individual genes in cells. There are many uses for this technology. CRISPR / Cas allows researchers to figure out the function of different genes. To do this, you just need to cut the gene under study from the DNA and study which functions of the body were affected.

Some practical applications systems:

Agriculture. Agricultural crops can be improved through CRISPR / Cas systems. Namely, to make them tastier and more nutritious, as well as heat-resistant. It is possible to endow plants with other properties: for example, to cut out the allergen gene from nuts (peanuts or hazelnuts).
Medicine, hereditary diseases. Scientists have the goal of using CRISPR / Cas to remove mutations from the human genome that can lead to diseases such as sickle cell anemia, etc. In theory, CRISPR / Cas can stop the development of HIV.
Gene drive. CRISPR / Cas can change not only the genome of an individual animal or plant, but also the gene pool of a species. This concept is known as "Gene drive"... Every living organism transfers half of its genes to its offspring. But the use of CRISPR / Cas can increase the probability of gene transfer by up to 100%. This is important in order for the desired trait to spread faster throughout the population.

Swiss scientists have significantly improved and modernized the CRISPR / Cas genome editing method, thereby expanding its capabilities. However, scientists could only modify one gene at a time using the CRISPR / Cas system. But now researchers at the Swiss Higher technical school Zurich have developed a method with which it is possible to simultaneously modify 25 genes in a cell.

For the latest technique, specialists used the Cas12a enzyme. For the first time in history, geneticists have successfully cloned monkeys. Popular Mechanics;

Nikolenko S. (2012). Genomics: problem statement and sequencing methods. "Postnauka".