Applied value of molecular biology. Molecular biologist

Molecular biology, Science, which owns its task, the knowledge of the nature of life phenomena by studying biological objects and systems at the level approaching molecular, and in some cases the achievement of this limit. The ultimate goal is to find out how and to what extent characteristic manifestations of life, such as heredity, reproduce themselves similar, protein biosynthesis, excitability, growth and development, storage and transfer of information, transformation of energy, mobility, etc. , 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. Distinctive feature of M. b. - study of life phenomena on non-living facilities or those who are inherent in the most primitive manifestations of life. These are biological education from cellular level and below: Subcellular organelles, such as insulated cell kernels, mitochondria, ribosomes, chromosome, cell membranes; Further - systems standing on the border of living and inanimate nature - viruses, including bacteriophages, and ending with molecules of the most important components of living matter - nucleic acids and proteins.

The foundation on which M. b was developed, was laid by such sciences as genetics, biochemistry, physiology of elementary processes, etc. According to the origins of its development, M. b. inextricably linked with molecular genetics, which continues to make an important part

Distinctive feature M. b. is its three-dimensionality. Essence of M. b. Watching M. Peruz to interpret biological functions in the concepts of the molecular structure. M. b. His task to get answers to the question "How," with the essence of the role and participation of the entire structure of the molecule, and to questions "why" and "why", finding out, on the one hand, the relationship between the properties of the molecule (again, first of all, proteins and nucleic acids) and the functions carried out by it and, on the other hand, the role of such individual functions in the overall complex of life manifestations.

Essential achievements molecular biology. This is not a complete list of these achievements: the disclosure of the structure and mechanism of the biological function of DNA, all types of RNA and Ribosomes, disclosure genetic code; opening reverse transcription, i.e. DNA synthesis on the RNA matrix; study of the mechanisms of functioning of respiratory pigments; Opening of the three-dimensional structure and its functional role in the action of enzymes, the principle of matrix synthesis and mechanisms of protein biosynthesis; disclosure of the structure of viruses and the mechanisms of their replication, primary and, partially, spatial structure of antibodies; isolation of individual genes, chemical, and then biological (enzymatic) gene synthesis, including human, out of cell (in vitro); transfer of genes from one organism to another, including in human cells; rapidly going to decipher the chemical structure of the increasing number of individual proteins, mainly enzymes, as well as nucleic acids; Detecting the phenomena of "self-assembly" of certain biological objects of ever-increasing complexity, ranging from nucleic acid molecules and moving to multicomponent enzymes, viruses, ribosomes, etc.; Filming up allotic and other basic principles of regulation biological functions and processes.

Tasks of molecular biology. Along with the important tasks of M. b. (knowledge of the laws of "recognition", self-assembly and integration) the current direction of scientific search of the nearest future is the development of methods that allow decipher the structure, and then a three-dimensional, spatial organization of high molecular nucleic acids. All the most important methods, the use of which provided the emergence and successes of M. b., 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 computer, synchrotron, or brake, radiation, laser technology, etc.) open up new opportunities for in-depth study of the problems of M. b. Among the most important tasks of a practical nature, the answer to which is expected from M. b., In the first place there is a problem of the molecular foundations of malignant growth, then the warning paths, and perhaps overcoming hereditary diseases - "molecular diseases". Of great importance will be to clarify the molecular bases of biological catalysis, i.e. the actions of enzymes. Among the most important modern directions of M. b. The desire to decipher the molecular mechanisms of the torch, toxic and medicinal substances, and also find out the details molecular structure and the functioning of such cell structures as biological membranes involved in the regulation of substances penetration and transport processes. More distant goals M. b. - knowledge of the nature of nervous processes, memory mechanisms, etc. One of the important emerging sections of M. b. - T. N. Genetic engineering, which places its task targeted operating in the genetic apparatus (genome) of living organisms, starting with microbes and lower (single-cell) and ending with a person (in the latter case, first of all, in order to radical treatment of hereditary diseases and correction of genetic defects).

The most important directions of MB:

- molecular genetics - study of the structural and functional organization of the genetic apparatus of cells and the mechanism for the implementation of hereditary information

- Molecular virology - study of molecular mechanisms of interaction of viruses with cells

- Molecular immunology - study of the patterns of immune responses of the body

- Molecular biology of development - the study of the appearance of varieties of cells during individual Development organisms and cell specialization

The main objects of the study are viruses (including bacteriophages), cells and subcellular structures, macromolecules, multicellular organisms.

It can be said that molecular biology explores the manifestations of life on non-living structures or systems with elementary signs of vital activity (which can be separate biological macromolecules, their complexes or organelles), studying, how key processes characterizing living matter are implemented through chemical interactions and transformations.

The allocation of molecular biology from biochemistry to an independent area of \u200b\u200bscience is dictated by the fact that its main task is to study the structure and properties of biological macromolecules involved in various processes, finding out the mechanisms of their interaction. Biochemistry is engaged in the study of the processes of vital activity, the patterns of their flow in the living organism and the conversion of molecules accompanying these processes. Ultimately, molecular biology is trying to answer the question, why this or that process occurs, while biochemistry answers the questions where and how the process considered in terms of chemistry occurs.

History

Molecular biology as a separate direction of biochemistry began to form in the 30s of the last century. It was then that for an in-depth understanding of the phenomenon of life there was a need for targeted studies on molecular level Processes of storage and transmission of hereditary information in living organisms. Then the task of molecular biology was determined in the study of the structure, properties and interaction of nucleic acids and proteins. The term "molecular biology" was first used by the English scientist William Astbury in the context of studies concerning the clarification of dependencies between the molecular structure and the physical and biological properties of fibrillar proteins, such as collagen, blood fibrin, or cutting muscle proteins.

At the dawn of the occurrence of molecular biology, RNA was considered component of plants and mushrooms, and DNA was considered as a typical component of animal cells. The first researcher who has proven that DNA is contained in plants, Andrei Nikolayevich Belozersky, who allocated DNA pea in 1935. This discovery established the fact that DNA is a universal nucleic acid present in plants and animal cells.

A serious achievement was the establishment of a direct causal relationship between genes and proteins. In their experiments, they subjected to neurographic cells ( Neurospora.crassa.) Retage irradiation that caused mutation. The results obtained showed that this led to a change in the properties of specific enzymes.

In 1940, Albert Claude allocated cytoplasmic RNA-containing granules from the cytoplasm of animal cells, which were less mitochondria. He called them microsomes. Subsequently, in the study of the structures and properties of the isolated particles, their fundamental role in the protein biosynthesis was established. In 1958, on the first symposium dedicated to these particles, it was decided to call these particles of ribosomes.

Another important step in the development of molecular biology has become published in 1944, the experimental data of Osvalda Everie, Colin Maclaud and McLeep, which showed that the cause of the transformation of bacteria is DNA. This was the first experimental proof of the DNA role in the transfer of hereditary information, which was debunked by the previously important idea of \u200b\u200bthe protein nature of genes.

In the early 50s, Frederick Sanger showed that the protein chain is a unique sequence of amino acid residues. In the late 50s, Max Perus and John Kendrew deciphered the spatial structure of the first proteins. Already in 2000, hundreds of thousands of natural amino acid sequences and thousands of spatial structures were known.

At about the same time, the study of Erwin Chargaffa allowed him to formulate the rules describing the ratio of nitrogenous bases in DNA (the rules say that, regardless of the species differences in DNA, the amount of guanin is equal to the amount of cytosine, and the amount of adenine is equal to the number of Temin), which helped to further make the greatest breakthrough in molecular biology and one of the greatest discoveries in biology in general.

This event occurred in 1953, when James Watson and Francis Creek, based on the works of Rosalind Franklin and Maurice Wilkins x-ray-structural analysis DNA, installed a two-weld structure of the DNA molecule. This discovery made it possible to answer the fundamental question about the ability of the carrier of hereditary information to self-reproduction and understand the mechanism of transmitting such information. The same scientists have been formulated by the principle of complementarity of nitrogenous bases, having a key importance for understanding the mechanism for the formation of supramolecular structures. This principle used now to describe all molecular complexes allows to describe and predict the conditions for the occurrence of weak (invaluable) intermolecular interactions, which determine the possibility of forming secondary, tertiary, etc. The structures of macromolecules, the flow of self-assembly of supramolecular biological systems that determine such a wide variety of molecular structures and their functional sets. At the same time, in 1953 there was a scientific journal of Journal of Molecular Biology. He was headed by John Kendry, sphere scientific interests which was the study of the structure of globular proteins ( Nobel Prize 1962 together with Max Peruz). A similar Russian-language magazine called "Molecular Biology" was founded in the USSR V. A. Engelhardt in 1966.

In 1958, Francis Creek formulated the so-called. Central Dogma Molecular Biology: an idea of \u200b\u200bthe irreversibility of the flow of genetic information from DNA via RNA to proteins according to DNA scheme → DNA (replication, creation of a copy of DNA), DNA → RNA (transcription, generation of genes), RNA → Protein (translation, decoding of structure information proteins). This dogma in 1970 was corrected somewhat correctly taking into account the accumulated knowledge, since the phenomenon of reverse transcription was opened independently Howard Toye and David Baltimore: an enzyme was discovered - a reverse case that is responsible for the implementation of reverse transcription - the formation of two-chain DNAs on a single-chain RNA matrix, which occurs from oncogenic viruses. It should be noted that the strict need of the flow of genetic information from nucleic acids to proteins is still the basis of molecular biology.

In 1957, Alexander Sergeevich Spirin together with Andrei Nikolayevich Belozersky showed that, with significant differences in the nucleotide composition of DNA from different organisms, the composition of the total RNA was similar. Based on these data, they came to the sensational conclusion that the total RNA cell can act as a carrier of genetic information from DNA to proteins, because it does not match it in its composition. At the same time, they noticed that there is a minor fraction of RNA, which fully corresponds to DNA in its nucleotide composition and which can be a true carrier of genetic infractions from DNA to proteins. As a result, they predicted the existence of relatively small RNA molecules, which are in the structure of the analogues of individual DNA sections and performing the role of intermediaries when transmitting genetic information contained in DNA in ribosomes, where protein molecules are synthesized using this information. In 1961 (S. Brenner, F. Jacob, M. Mesheselson on one side and F. Gro, Francois Jacob and Jacques Mono were the first to have experienced confirmation of the existence of such molecules - information (matrix) RNA. Then they developed the concept and model of functional DNA Opero units, which made it possible to explain exactly how to regulate the expression of genes in prokaryotes. Study of the mechanisms of protein biosynthesis and the principles of the structural organization and operation of molecular machine-ribosomes - made it possible to formulate the postulate describing the movement of genetic information called the central dogma of molecular biology: DNA - DNA IRNK - protein.

In 1961, and for the next few years, Heinrich Matteha and Marshall Nirenberg, and then Kharom Korana and Robert Holly were held several work on deciphering the genetic code, as a result of which the immediate relationship between the DNA structure and the synthesized proteins was established and the nucleotide sequence determines A set of amino acids in protein. Also obtained data on the universality of the genetic code. The discoveries were noted by the Nobel Prize of 1968.

For development modern ideas On the RNA functions, the discovery of non-corrective RNAs, made by Alexander Sergeevich Spin, jointly with Andrei Nikolayevich Belozersky, 1958, Charles Brenner with co-authors and Spacelman Sollar, 1961. This type of RNA is the main part of cell RNA. The unexperturing primarily includes ribosomal RNA.

Methods of cultivation and hybridization of animal cells obtained serious development. In 1963, Francois Jacob and Sydnema Benner were formulated by the ideas about the replica - sequences inherently replicating genes explaining the important aspects of the regulation of the replication of genes.

In 1967, in the laboratory A. S. Spirin was first demonstrated that the form of a compactly cooled RNA determines the morphology of the ribosomal particle.

In 1968, a significant fundamental discovery was made. The provision, finding the DNA fragments of the retarding chain in the study of the replication process, named in honor of it by fragments of the provision, clarified the DNA replication mechanism.

In 1970, there was a significant discovery independently to Howard and David Baltimore: a significant opening enzyme was discovered, which is responsible for the implementation of reverse transcription - the formation of double-chain DNA on a single-chain RNA matrix, which occurs in oncogenic viruses containing RNA.

Another important achievement of molecular biology was the explanation of the mechanism of mutations at the molecular level. As a result of a series of studies, the main types of mutations were established: duplication, inversions, deletions, translocations and transpositions. This made it possible to consider evolutionary changes from the point of view of gene processes, made it possible to develop the theory of molecular hours, which is used in phyloge.

By the beginning of the 70s, the basic principles of functioning of nucleic acids and proteins in a living organism were formulated. It was found that proteins and nucleic acids in the body are synthesized by the matrix mechanism, the matrix molecule carries the encrypted information about the sequence of amino acids (in protein) or nucleotides (in nucleic acid). When replicating (DNA doubling) or transcription (Synthesis of the IRNA), the DNA is served by such a matrix, when broadcasting (protein synthesis) or reverse transcription - IRNA.

Thus, theoretical prerequisites were created for the development of applied directions of molecular biology, in particular, genetic engineering. In 1972, Paul Berg, Herbert Boer and Stanley Cohen developed molecular cloning technology. Then they were first obtained in the tube recombinant DNA. These outstanding experiments laid the foundations of genetic engineering, and this year is considered the date of birth of this scientific direction.

In 1977, Frederick Sanger, and independently Allan Maxam and Walter Gilbert developed various methods for determining the primary structure (sequencing) of DNA. Singer Method, the so-called chain break method is the basis of the modern sequencing method. The principle of sequencing is based on the use of labeled bases acting as terminators in a cyclic sequencing reaction. This method was widespread due to the ability to quickly analyze.

1976 - Frederick. Sanger has decrypted the nucleotide sequence of the Phage φχ174 DNA of 5375 nucleotide pairs.

1981 - Sickle-cell anemia becomes the first genetic disease diagnosed by DNA analysis.

1982-1983 Opening of the catalytic RNA function in American laboratories T. Check and S. Oltman changed the existing idea of \u200b\u200bthe exceptional role of proteins. By analogy with catalytic proteins - enzymes, catalytic RNAs were called ribosis.

1987 Carey Mulletis opened a polymerase chain reaction, due to which it is possible to artificially significantly increase the number of DNA molecules in solution for further work. To date, this is one of the most important methods of molecular biology, used in the study of hereditary and viral diseases, when studying genes and in the genetic identification of the individual and establishing kinship, etc.

In 1990, at the same time three groups of scientists published a method that allowed the synthetic functionally active RNA in the laboratory of synthetic functionally active RNA (artificial ribosis or molecules interacting with various ligands - aptamers). This method was called "Evolution in a test tube". And soon after that, in 1991-1993 in the laboratory A.B. Chetverina was experimentally shown the possibility of existence, growth and amplification of RNA molecules in the form of colonies on solid media.

In 1998, almost simultaneously Craig Melo and Andrew Faer described previously observed with genetic experiments with bacteria and colors RNA interference, in which a small two-stranded molecule of RNA leads to a specific suppression of gene expression.

The opening of the RNA interference mechanism has very important practical importance for modern molecular biology. This phenomenon is widely used in scientific experiments As a tool for "shutdown", that is, suppressing the expression of individual genes. Of particular interest is caused by the fact that this method allows to carry out the reversible (temporary) suppression of the activity of the studied genes. Studies are underway the possibility of using this phenomenon for the treatment of viral, tumor, degenerative and metabolic diseases. It should be noted that in 2002 mutants of polio viruses were opened, capable of avoiding RNA interference, therefore, even painstaking work is required to develop truly effective treatment methods based on this phenomenon.

In 1999-2001, several groups of researchers were determined with a resolution of 5.5 to 2.4 angstroms the structure of bacterial ribosomes.

Thing

Achievements of molecular biology in knowledge of wildlife is difficult to overestimate. Large success managed to achieve thanks to a successful concept of research: complex biological processes are considered from the position of individual molecular systems, which makes it possible to apply accurate physicochemical research methods. It also attracted a lot of great minds from related directions to this area of \u200b\u200bscience: chemistry, physics, cytology, virology, which also has a beneficial effect on the scope and speed of scientific knowledge in this area. Such significant discoveries as the definition of the DNA structure, the deciphering of the genetic code, the artificial directional modification of the genome, made it possible to significantly deeper the specifics of the processes of the development of organisms and successfully solve the numerous most important fundamental and applied scientific, medical and social tasks, which were not yet considered insoluble.

The subject of study of molecular biology is mainly proteins, nucleic acids and molecular complexes (molecular machines) on their basis and the processes in which they participate.

Nucleic acids are linear polymers consisting of nucleotide links (compounds of five-membered sugar with a phosphate group with a fifth cycle atom and one of four nitrogen bases) interconnected by the ester bond of phosphate groups. Thus, nucleic acid is a pentosophosphate polymer with nitrogen bases as side substituents. The chemical composition of the RNA chain differs from DNA in that the first consists of a five-membered carbohydrate cycle of ribose, while the second is from dehydroxyllated derivative of ribose - deoxyribose. In this case, the spatially these molecules differ dramatically, since RNA is a flexible single-chain molecule, while DNA is a two-chain molecule.

Proteins are linear polymers that are chains of alpha-amino acids connected by a peptide bond, from where their second name is polypeptides. The composition of natural proteins includes many different amino acid units - in humans up to 20 -, which determines the wide variety of functional properties of these molecules. Those or other proteins take part in almost every process in the body and perform many tasks: play the role of cellular building material, provide transportation of substances and ions, catalyzed chemical reactions- This list is very long. Proteins form stable molecular conformations of various levels of organization (secondary and tertiary structures) and molecular complexes, which is even more expanding their functionality. These molecules can have a high specificity to perform any tasks due to the formation of a complex spatial globular structure. A wide variety of proteins ensures the constant interest of scientists to this type of molecules.

Modern ideas about the subject of molecular biology are based on a generalization, nominated for the first time in 1958 by Francis Crycus as a central dogma of molecular biology. Its essence consisted in approval that genetic information in living organisms undergoes strictly certain stages of implementation: copying from DNA in DNA inheritance, from DNA to RNA, and then from RNA to protein, and the reverse transition does not implement. This statement was fairly only from the part, therefore, subsequently, the central dogma was corrected with a loan to those opened new data.

At the moment, several ways to implement genetic material representing various sequences of the implementation of three types of genetic information are known: DNA, RNA and protein. In nine possible implementation paths, three groups are distinguished: these are three common transformations (general), which are normally implemented in most living organisms; Three special transformations (Special), carried out in some viruses or in special laboratory conditions; Three unknown transformations (UNKNOWN), the implementation of which is considered impossible.

The general transformation includes the following ways of implementing the genetic code: DNA → DNA (replication), DNA → RNA (transcription), RNA → Protein (broadcast).

To carry out the transfer of hereditary features, parents need to transmit the descendants a complete DNA molecule. The process, due to which, based on the original DNA, its exact copy can be synthesized, and therefore, the genetic material can be transmitted, called replication. It is carried out by special proteins that shave the molecule (straighten its site), double-spiral spirals, and with the help of DNA polymerase, create an exact copy of the original DNA molecule.

To ensure the livelihoods of the cell, it must be constantly accessing the genetic code laid down in the DNA double helix. However, this molecule is too large and vague to use it as a direct source of genetic material for continuous protein synthesis. Therefore, during the implementation of information laid in DNA, there is a mediation stage: Synthesis of IRNA, which is a small single-stranded molecule, complementary to a certain cutting of DNA encoding some protein. The transcription process is provided by RNA polymerase and transcription factors. The resulting molecule can then be easily delivered to the cell department responsible for protein synthesis - ribosome.

After entering and RNA, the final stage of the implementation of genetic information comes in Ribosoma. At the same time, the ribosome reads with IRNA genetic code with triplets called codons and synthesizes the corresponding protein on the basis of the information obtained.

During the special transformations, the genetic code is implemented according to the RNA scheme → RNA (replication), RNA → DNA (reverse transcription), DNA → Protein (live broadcast). Replication of this species is implemented in many viruses, where it is carried out by an enzyme RNA-dependent RNA polymerase. Similar enzymes are also in eukaryotes, where they are associated with the RNA-Justification process (Silencing). Reverse transcription is detected in retroviruses, where it is carried out under the action of the reverse transcriptase enzyme, as well as in some cases in eukaryotic cells, for example, with telomeric synthesis. Live broadcast is carried out only in artificial conditions in an isolated system outside the cell.

Any of three possible genetic information transitions from protein in protein, RNA or DNA is considered impossible. The case of exposure to prions on proteins, as a result of which a similar prion is formed, it could be reasonably attributed to the type of genetic information of protein → protein. However, it is not formal, because does not affect the amino acid sequence in protein.

The history of the emergence of the term "Central Dogma" is curious. Since the word dogma in general means a statement that is not doubtful, and the word itself has an explicit religious subtext, choosing it as a description scientific fact Not quite legitimate. According to the Francis Creek itself, it was his mistake. He wanted to give an extended theory of greater significance, allocate it against the background of other theories and hypotheses; For which it decided to use this majestic, according to his representation, the Word, without understanding its true meaning. The name is, however, gothes.

Molecular biology today

The rapid development of molecular biology, constant interest in achievements in this area by the Company and the objective importance of research led to the emergence of a large number of major research centers of molecular biology worldwide. Among the largest should be mentioned as follows: Laboratory of Molecular Biology in Cambridge, Royal Institute in London - in the UK; Institutes of Molecular Biology in Paris, Marseille and Strasbourg, Pasteur Institute - in France; Molecular biology departments at Harvard University and Massachusetts Institute of Technology, University in Berkeley, in the California Institute of Technology, at Rockefeller University, at the Institute of Health in Beteses - in the United States; Institutes of Max Planck, Universities in Gottingen and Munich, Central Institute of Molecular Biology in Berlin, Institutes in Jena and Halle - in Germany; Caroline Institute in Stockholm in Sweden.

In Russia, the leading centers in this area are the Institute of Molecular Biology. V.A.Englgardt RAS, Institute of Molecular Genetics of the Russian Academy of Sciences, Institute of Biology, Gena RAS, Institute of Physico-Chemical Biology. A.N. Belozersky Moscow State University. M.V. Lomonosov, Institute of Biochemistry. A.N.Bach RAS and the Institute of Protein of the Russian Academy of Sciences in Pushchino.

Today, the area of \u200b\u200binterests of molecular biologists covers a wide range of fundamental scientific issues. Study of the structure of nucleic acids and protein biosynthesis, the structure of the structure and functions of various intracellular structures, and cell surfaces occupies the leading role. Also important areas of research are the study of the mechanisms of reception and transmission of signals, molecular mechanisms of transport of compounds inside the cell as well as from the cell to the external environment and back. In the country's main directions of scientific search in the field of applied molecular biology, one of the most priorities is the problem of occurrence and development of tumors. Also, a very important direction, the study of which the section of molecular biology is engaged in molecular genetics, is the study of the molecular basis of the emergence of hereditary diseases, and viral diseases, such as AIDS, as well as the development of ways to prevent them and, possibly, treatment at the gene level. Widespread uses found the discovery and development of molecular biologists in forensic medicine. The real revolution in the field of identification of the personality was made in the 1980s by scientists from Russia, the USA and Great Britain, thanks to the development and implementation of the method of "genomic dactyloscopy" in the daily practice of the DNA personality. Studies in this area are not stopped to this day, modern methods allow you to establish a person with a probability of a mistake one billion percent. Already now there is an active development of the project of a genetic passport, which is supposed to be allowed to strongly reduce the crime rate.

Methodology

Today, molecular biology has an extensive arsenal methods that allow solving the most advanced and most complex tasks facing scientists.

One of the most common methods in molecular biology is gel electrophoresiswhich solves the problem of separation of a mixture of macromolecules in size or by charging. Almost always, after the separation of macromolecules in the gel, blotting is used, a method that allows you to transfer macromolecules from the gel (sorbit) to the surface of the membrane for convenience of further working with them, in particular hybridization. Hybridization is the formation of hybrid DNA of two chains having a different nature - a method that plays an important role in fundamental studies. It is used to determine complementary Segments in different DNA (DNA of different species), with its help the search for new genes occurs, with its help, an interference was opened, and its principle is based on genomic dactyloscopy.

A greater role in the modern practice of molecular biological research is played by the sequencing method - determining the sequence of nucleotides in nucleic acids and amino acids in proteins.

Modern molecular biology cannot be represented without a polymerase chain reaction method (PCR). Thanks to this method, an increase in the amount (amplification) of copies of some DNA sequence is carried out to make a sufficient amount of substance from one molecule to work with it. A similar result is achieved by molecular cloning technology, in which the required nucleotide sequence is introduced into the Bacteria DNA (living systems), after which the reproduction of bacteria leads to the desired result. This approach is technically much more complicated, but it allows you to simultaneously obtain the result of the expression of the nucleotide sequence under study.

Ultracentrifugation methods are widely used in molecular biological studies (for separation of macromolecules (large quantities), cells, organelles), methods of electron and fluorescent microscopy, spectrophotometric methods, x-ray structural analysis, autoradiography, and the like.

Thanks to technical progress and scientific research in the field of chemistry, physics, biology and computer science, modern equipment allows you to allocate, study and change individual genes and processes in which they are involved.

31.2

For friends!

reference

Molecular biology has grown from biochemistry in April 1953. Its appearance is connected with the names of James Watson and Francis Cry, which opened the structure of the DNA molecule. The discovery was made possible by the study of genetics, bacteria and biochemistry of viruses. Profession The molecular biologist is not widespread, but today its role in modern society Very great. A large number of Diseases, including manifesting at the genetic level, requires scientists to find solutions to this problem.

Description of activity

Viruses and bacteria constantly mutate, which means that a person cease to help medicines and diseases become difficult. The task of molecular biology is to get out of this process and develop a new remedy for diseases. Scientists work according to the well-defined scheme: blocking the causes of the disease, elimination of heredity mechanisms and make it easier for the patient's condition. There are a number of centers, clinics and hospitals in the world, where molecular biologists to help patients are developing new treatments.

Labor duties

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

Features of career growth

Profession The molecular biologist is quite promising in its field and today claims the first places in the ranking of the medical professions of the future. By the way, the molecular biologist is not necessarily all the time to remain in this area. If there is a desire to change the generation of classes, it can retrain into laboratory equipment sales managers, start developing instruments for various studies or open your business.

Molecular biology has survived a period of rapid development of its own research methods, which is now different from biochemistry. In particular, it includes methods of genetic engineering, cloning, artificial expression and nocause of genes. Since the DNA is a material carrier of genetic information, molecular biology has become very close to genetics, and molecular genetics was formed at the same time, which is simultaneously a section of genetics and molecular biology. Just as molecular biology uses viruses as a study tool, in virology, molecular biology methods are used to solve their tasks. Computational techniques are involved in the analysis of genetic information, and therefore new directions of molecular genetics appeared, which are sometimes considered by special disciplines: bioinformatics, genomics and proteomics.

History of development

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

In 1928, Frederick Griffith first showed that the extract of killed by heating pathogenic bacteria can transmit a sign of pathogenicity by non-hazardous bacteria. The study of the transformation of bacteria in the future led to the purification of a pathogenic agent, which, contrary to expectations, was not protein, but nucleic acid. Nucleic acid itself is not dangerous, it only transfers the genes that determine the pathogenicity and other properties of the microorganism.

In the 50s of the 20th century it was shown that the bacteria has a primitive sexual process, they are able to exchange extrachromosomal DNA, plasmids. The discovery of plasmid, as well as transformation, was based on the plasmid technology distributed in the molecular biology. Another important discovery for the methodology was the detection at the beginning of the 20th century viruses of bacteria, bacteriophages. Phages can also carry genetic material from one bacterial cell to another. Infection of bacteria by the phages leads to a change in the composition of the bacterial RNA. If without phages, the composition of RNA is similar to the composition of bacteria DNA, then after infection of RNA becomes more like DNA bacteriophage. Thus, it was found that the RNA structure is determined by the DNA structure. In turn, the rate of protein synthesis in cells depends on the number of RNA protein complexes. So it was formulated central Dogma Molecular Biology: DNA ↔ RNA → Protein.

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

see also

  • Molecular biology (magazine)
  • Transcriptomic
  • Molecular Paleontology
  • EMBO - European organization of molecular biologists

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. Expression of genes. - M.: Science, 2000. - 000 s., Il. ISBN 5-02-001890-2

Links


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    MOLECULAR BIOLOGY - studies the phenomena of life at the level of macromolecules (ch. Programs and nucleic to T) in cell-free structures (ribosomes, etc.), in viruses, as well as in cells. Object M. b. Setting the role and mechanism of the functioning of these macromolecules based on ... ... Chemical encyclopedia

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

Books

  • Molecular biology cells. Collection of tasks, J. Wilson, T. Hunt. The book of American authors - Appendix KO 2 - MUSH edition of the textbook `Molecular biology of cells` B. Alberts, D. Breya, J. Lewis, etc. contains questions and tasks whose goal is to deepen ...

Molecular biology

science, which owns its task, the knowledge of the nature of life phenomena by studying biological objects and systems at the level approaching molecular, and in some cases the achievement of this limit. The ultimate goal is to find out how and to what extent characteristic manifestations of life, such as heredity, reproduce themselves similar, protein biosynthesis, excitability, growth and development, storage and transfer of information, transformation of energy, mobility, etc. due to the structure, properties and interaction of biologically important molecules, primarily two main classes of high molecular weight biopolymers (see biopolymers) - proteins and nucleic acids. Distinctive feature of M. b. - study of life phenomena on non-living facilities or those who are inherent in the most primitive manifestations of life. These are biological formations from the cellular level and below: subcellular organelles, such as insulated cell kernels, mitochondria, ribosomes, chromosome, cell membranes; Next - systems standing on the border of living and inanimate nature - viruses, including bacteriophages, and ending with molecules of the most important components of living matter - nucleic acids (see nucleic acids) and proteins (see proteins).

M. b. - A new scope of natural science, closely related to the long-established areas of studies, which are covered by biochemistry (see biochemistry), biophysics (see biophysics) and bioorganic chemistry (see bioorganic chemistry). The distinction here is only possible on the basis of accounting of the methods used and on the principal nature of the approaches used.

The foundation on which M. b was developed, was laid by such sciences as genetics, biochemistry, physiology of elementary processes, etc. According to the origins of its development, M. b. Insiscimulating with molecular genetics (see Molecular Genetics) , which continues to make an important part of M. b., although it has been formed already largely in independent discipline. EXECUTION M. B. From biochemistry dictated by the following considerations. The tasks of biochemistry are mainly limited to the statement of the participation of certain chemical substances with certain biological functions and processes and clarifying the nature of their transformations; The leading value belongs to information about the reactivity and the main features of the chemical structure expressed by the usual chemical formula. T. about., Essentially, attention is focused on transformations affecting the main challenges. Meanwhile, L. Pauling Om is underlined , in biological systems and manifestations of vital activity should be allocated by non-comprehensive bonds acting within the same molecule, but a variety of types of bonds that cause intermolecular interactions (electrostatic, van der Waals, hydrogen bonds, etc.).

The final result of the biochemical study can be represented in the form of a system of chemical equations, usually completely exhaustable by their image on the plane, i.e. in two dimensions. A distinctive feature of M. b. is its three-dimensionality. Essence of M. b. M. Perus is seen to interpret biological functions in the concepts of the molecular structure. It can be said that if before, when studying biological objects, it was necessary to answer the question "that", that is, what substances are present, and the question "where" - in which tissues and organs, then M. b. puts his task to get answers to the question "how", bringing the essence of the role and participation of the entire structure of the molecule, and to questions "why" and "why", finding out, on the one hand, the relationship between the properties of the molecule (again, first of all, proteins and nucleic acids) and the functions carried out by it and, on the other hand, the role of such individual functions in the overall complex of life manifestations.

The crucial role is acquired by the mutual arrangement of atoms and their groupings in common Structure Macromolecules, their spatial relationships. This applies to both individual, individual, components and the overall configuration of the molecule as a whole. It is as a result of the occurrence of a strictly deterministic volume structure of a biopolymer molecule acquire those properties, by virtue of which they turn out to be able to serve as the material basis of biological functions. This principle of approach to the study of living is the most characteristic, typical line M. b.

Historical reference. The vast importance of the research of biological problems at the molecular level foresaw I. P. Pavlov , who talked about the last stage in the science of life - the physiology of a living molecule. The term "M. b. " The English was used for the first time. Scientific U. Astbury in annex to research related to the clarification of dependencies between the molecular structure and the physical and biological properties of fibrillar (fibrous) proteins, such as collagen, blood fibrin, or muscle contractile proteins. Widely apply the term "M. b. " steel from the beginning of the 50s. 20 V.

The emergence of M. b. As the formated science is customary to 1953, when J. Watson Om and F. Creek Om in Cambridge (United Kingdom) disclosed a three-dimensional structure of deoxyribonucleic acid (see Deoxyribonucleic acid) (DNA). This made it possible to talk about how the details of this structure determine the biological functions of DNA as a material carrier of hereditary information. In principle, the DNA has become known somewhat earlier about this role (1944) as a result of the works of American genetics O. T. Avery with employees (see molecular genetics), but it was not known to which the extent to which this function depends on the molecular structure of DNA. This was only possible after in the laboratories of U. L. Bragg (see Bragg - Wulf Condition), J. Bernal A, and others. New principles of x-ray structural analysis were developed, which provided the use of this method for the detailed knowledge of the spatial structure of the macromolecules of proteins and nucleic acids.

Levels of a molecular organization. In 1957, Kendrew installed the three-dimensional structure of Mioglobin A , And in subsequent years, this was done by M. Peruz against hemoglobin a. The ideas about various levels of the spatial organization of the macromolecule 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. Linear, filamentous biofolymer molecule as a result of hydrogen bonds, has the ability to fit in a certain way in space, for example, in the case of proteins, as L. Poling showed, to acquire the shape of the helix. This is denoted as a secondary structure. About the tertiary structure say when a molecule possessing secondary structureIt is further folded in one way or another, filling the three-dimensional space. Finally, molecules with three-dimensional structure can enter into interaction, naturally located in space relative to each other and forming what is denoted as a quaternary structure; Its individual components are usually called subunits.

The most visual example of how the molecular three-dimensional structure determines the biological functions of the molecule, serves as DNA. It possesses the structure of a double spiral: two threads coming in the opposite direction (anti-parallel), one around another, forming a double helix with a mutually complementary location of the base, i.e. so that against a certain base of one chain always in another chain base that the best way Provides the formation of hydrogen bonds: Adepine (a) forms a pair with thymine (T), guanine (g) - with cytosine (C). Such a 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 dividing the thread cell of the double spiral of DNA, which serves as a matrix, or template, mutate and on each of them, a complementary new thread is synthesized under the action of enzymes. As a result of this, two properly identical daughter molecules (see Cell, Mitz) are obtained from one DNA Mother Molecule.

Also, in the case of hemoglobin, it turned out that its biological function - the ability to reversibly attach oxygen into lungs and then to give it to tissues - is closely associated with the peculiarities of the three-dimensional structure of hemoglobin and its changes in the process of implementing the physiological role in effect. When binding and dissociation O 2, spatial changes of the conformation of the hemoglobin molecule occur, leading to a change in the affinity of the iron atoms contained in it to oxygen. The changes in the size of the hemoglobin molecule, reminiscent of the changes in the amount of the chest during breathing, allowed to name the hemoglobin "molecular light".

One of the most important features of living objects is their ability to finely adjust all the manifestations of life. Major contribution M. b. In scientific discoveries, it is necessary to consider the disclosure of a new, previously unknown regulatory mechanism, denoted as altogetherteric effect. It consists in the ability of substances of low molecular weight - so on. Ligands - modify the specific biological functions of macromolecules, primarily catalytically active proteins - enzymes, hemoglobin, receptor proteins involved in the construction of biological membranes (see biological membranes), in synaptic transmission (see synapses), etc.

Three biotic flux.In the light of the representations of M. b. The set of life phenomena can be viewed as a result of a combination of three streams: the flow of matter, which is its expression in metabolic phenomena, i.e. assimilation and dissimulation; The stream of energy that is driving power for all manifestations of vital activity; and the flow of information that penetrates not only the diversity of the development and existence of each organism, but also a continuous series of generations of replacing each other. It is the idea of \u200b\u200bthe flow of information made into the doctrine of the living world by the development of M. b., Imposes its specific, unique imprint on it.

The most important achievements of molecular biology. Swirling, scope and depth of influence M. b. For success in the knowledge of the indigenous problems, the study of wildlife is fairly compared, for example, with the influence of quantum theory on the development of atomic physics. Two internally related conditions determined this revolutionizing effect. On the one hand, the decisive role played the detection 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 result of the specified circumstance, there was a rapid inclusion of a significant number of representatives exact Sciences - Physicists, chemists, crystallographs, and then mathematicians - in the development of biological problems. In its aggregate, these circumstances have led to an unusually rapid pace of development M. b., The number and significance of its success achieved in just two decades. This is not a complete list of these achievements: the 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 the code genetic) ; Opening reverse transcription (see Transcription) , i.e. DNA synthesis on the RNA matrix; study of the mechanisms of functioning of respiratory pigments; Opening of the three-dimensional structure and its functional role in the action of enzymes (see Enzymes) , principle of matrix synthesis and mechanisms of protein biosynthesis; Disclosure of the structure of viruses (see viruses) and the mechanisms of their replication, primary and, partially, the spatial structure of antibodies; Isolation of individual genes , chemical, and then biological (enzymatic) synthesis of gene, including human, out of cell (in vitro); transfer of genes from one organism to another, including in human cells; rapidly going to decipher the chemical structure of the increasing number of individual proteins, mainly enzymes, as well as nucleic acids; Detecting the phenomena of "self-assembly" of certain biological objects of ever-increasing complexity, ranging from nucleic acid molecules and moving to multicomponent enzymes, viruses, ribosomes, etc.; Filming up allotic and other basic principles for regulating biological functions and processes.

Reductionism and integration. M. b. It is the final stage of that direction in the study of living objects, which is denoted as "reductionism", i.e. the desire to reduce complex life functions to phenomena flowing at the level of molecules and therefore accessible to the study of physics and chemistry methods. Achieved by M. b. Successes indicate the effectiveness of this approach. At the same time, it is necessary to take into account that in natural conditions in the cell, fabric, organ, and the whole body we are dealing with systems of an increasing degree of complication. Such systems are formed from the lower level components by their regular integration in the integrity, acquiring a structural and functional organization and possess new properties. Therefore, as knowledge of the laws about the patterns available to disclosure on molecular and adjoining levels, in front of M. b. The tasks of the knowledge of the integration mechanisms as a line of further development in the study of life phenomena. The starting point here serves as a study of the forces of intermolecular interactions - hydrogen bonds, van der Waals, electrostatic forces, etc., and so on. His totality and spatial location, they form what can be designated as "integrative information". It should be seen as one of the main parts of the information mentioned. In the region of M. b. An examples of integration can be the phenomena of self-assembly of complex formations from the mixture of their components. This includes, for example, the formation of multicomponent proteins from their subunits, the formation of viruses from their component parts - proteins and nucleic acid, restoration of the original ribosome structure after separating their protein and nucleic components, etc. The study of these phenomena is directly related to the knowledge of the main phenomena " recognition »Molecules of biopolymers. We are talking about finding out which combinations of amino acids - in protein or nucleotide molecules - in nucleic acids interact with each other in the processes of the association of individual molecules to form complexes of strictly specific, injecting the specified composition and structure. This includes the processes of formation of complex proteins from their subunits; Further, selective mutualization between molecules of nucleic acids, such as transport and matrix (in this case, significantly expanded our information disclosure of the genetic code); Finally, this is the formation of many types of structures (for example, ribosomes, viruses, chromosomes), in which proteins and nucleic acids are also involved. The disclosure of the relevant patterns, the knowledge of the "language" underlying the specified interactions is one of the most important areas of M. b., Still awaiting its development. This area is considered as belonging to the number of fundamental problems for the entire biosphere.

Tasks of molecular biology. Along with the important tasks of M. b. (knowledge of the laws of "recognition", self-assembly and integration) the current direction of scientific search of the nearest future is the development of methods that allow decrypting the structure, and then a three-dimensional, spatial organization of high molecular weight nucleic acids. At this time, this is achieved in relation to the total plan of the three-dimensional structure of DNA (double helix), but without the exact knowledge of its primary structure. Fast successes in the development of analytical methods make it possible to wait for the achievement of these goals over 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 provided the emergence and successes of M. b., 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 computer, synchrotron, or brake, radiation, laser technology, etc.) open up new opportunities for in-depth study of the problems of M. b. Among the most important tasks of a practical nature, the answer to which is expected from M. b., In the first place there is a problem of the molecular foundations of malignant growth, then the warning paths, and perhaps overcoming hereditary diseases - "molecular diseases" (see molecular diseases ). Of great importance will be to clarify the molecular bases of biological catalysis, i.e. the actions of enzymes. Among the most important modern directions of M. b. The desire to decipher the molecular mechanisms of the action of hormones (see hormones) , Toxic and drug substances, as well as to find out the details of the molecular structure and the functioning of such cell structures, as biological membranes involved in the regulation of the processes of penetration and transport substances. More distant goals M. b. - knowledge of the nature of nervous processes, memory mechanisms (see Memory), etc. One of the important emerging sections of M. b. - T. N. Genetic engineering, which places its task, targeted by the genetic apparatus (the genome OM) of living organisms, starting with microbes and lower (single-cell) and ending with a person (in the latter case, first of all, in order to radical treatment of hereditary diseases (see hereditary diseases) and correction of genetic defects ). About more extensive interventions in the genetic basis of a person can only be part of a more or less distant future, since it arises serious obstacles to both technical and principled nature. In relation to microbes, plants, and possibly S.-H. Animals such perspectives are very encouraging (for example, obtaining varieties of cultivated plants with a nitrogen fixation apparatus from air and do not need fertilizer). They are based on success already achieved: the isolated and synthesis of genes, the transfer of genes from one organism to another, the use of mass cultures of cells as producers of economic or medical important substances.

Organization of research on molecular biology. Fast development M. b. He led to the emergence of a large number of specialized research centers. The amount of them rapidly increases. The largest: in the UK - a laboratory of molecular biology in Cambridge, Royal Institute in London; In France - Institutes of Molecular Biology in Paris, Marseille, Strasbour, Pasteur Institute; In the US - Departments of M. b. At universities and institutes in Boston (Harvard University, Massachusetts technological Institute), San Francisco (Berkeley), Los Angeles (California Institute of Technology), New York (Rockefeller University), Health Institutes in Betsed, etc.; In Germany - Institutes of Max Planck, Universities in Gottingen and Munich; in Sweden - Caroline Institute in Stockholm; In the GDR - Central Institute of Molecular Biology in Berlin, Institutes in Jena and Galle; In Hungary - Biological Center in Szeged. In the USSR, the first specialized Institute M. B. was created in Moscow in 1957 in the USSR Academy of Sciences (see ); Then were formed: the Institute of Bioorganic Chemistry of the USSR Academy of Sciences of the USSR in Moscow, the Institute of Protein in Pushchina, Biological Department at the Institute of Atomic Energy (Moscow), Departments of M. B. At the Institutions of the Siberian Branch of the Academy of Sciences in Novosibirsk, the Interfaculty Laboratory of Bioorganic Chemistry of Moscow State University, the Sector (then Institute) of Molecular Biology and Genetics of the USSR Academy of Sciences in Kiev; Significant work on M. b. Lead at the Institute high molecular weight connections In Leningrad, in a number of departments and laboratories of the Academy of Sciences of the USSR and other departments.

Along with individual research centers, there were organizations a wider scale. In Western Europe, the European Organization for M. B. (EMBO), in which over 10 countries participates. In the USSR, at the Institute of Molecular Biology in 1966, the Scientific Council on M. B., which is coordinating and organizing the center in this area of \u200b\u200bknowledge. They released an extensive series of monographs on the most important sections of M. b., "Winter Schools" on M. b., Conferences and symposia on topical issues of M. b are held regularly. In the future, scientific advice on M. b. Created at the AMN of the USSR and many Republican Academy of Sciences. From 1966 there is a magazine "Molecular biology" (6 issues per year).

For a relatively short term in the USSR, a significant detachment of researchers in the field of M. B was grew; These are a senior generation scientists who partially switched their interests from other regions; In the main mass, these are numerous young researchers. From among the leading scientists who adopted active participation in the formation and development of M. b. In the USSR, it is possible to name such as A. A. Baev, A. N. Belozersky, A. E. Braunstein, Yu. A. Ovchinnikov, A. S. Spirin, M. M. Shemyakin, V. A. Engelgardt. New achievements M. b. And the molecular genetics will be facilitated by the decision 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-Differ and A., Bioenergetics, per. from English, M., 1960; Anfinsen K., Molecular Basics of Evolution, Per. from English, M., 1962; Stanley W., Walenes E., viruses and nature of life, feathers. from English, M., 1963; Molecular genetics, per. from. English, Part 1, M., 1964; Volkenstein M. V., Molecules and Life. Introduction to molecular biophysics, M., 1965; Gaurovits F., Chemistry and proteins, feathers. from English, M., 1965; Bresler S. E., Introduction to molecular biology, 3 ed., M. - L., 1973; Ingram V., Biosynthesis Macromolecules, Per. from English, M., 1966; Engelgardt V. A., Molecular Biology, In the CN: Biology Development in the USSR, M., 1967; Introduction to molecular biology, per. from English, M., 1967; Watson J., Molecular Biology of Gene, Per. from English, M., 1967; Finean J., Biological Ultrastructures, Per. from English, M., 1970; Bendall J., muscles, molecules and movement, per. from English, M., 1970; Oh, M., Biological code, per. from English, M., 1971; Molecular biology of viruses, M., 1971; Molecular basics of protein biosynthesis, M., 1971; Bernhard C., Structure and Enzyme Function, Per. from English, M., 1971; Spirin A. S., Gavrilova L. P., Ribosome, 2 ed., M., 1971; Frankel-Konrat H., Chemistry and biology of viruses, per. from English, M., 1972; Smith K., Henouwt F., Molecular photobiology. Inactivation and recovery processes, per. from English, M., 1972; Harris, the basics of the biochemical genetics of a person, lane. from English, M., 1973.

V. A. Engelgardt.


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

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