molecular biology, scientific study of the molecular basis of life processes, including cellular respiration, excretion, and reproduction. The term molecular biology was coined in 1938 by Warren Weaver, then director of the natural sciences program at the Rockefeller Foundation. In 1950 W. T. Astbury of the Univ. of Leeds used the term in its now accepted sense, to describe the area of research, closely related to and often overlapping biochemistry, conducted by biologists whose approach to and interest in biology are principally at the molecular level of organization. The field of molecular biology has grown with the increasing sophistication of available techniques and has quickly built upon its own increases in the understanding of biological processes. In the 1930s, with the help of the technique of ultracentrifugation, the macromolecules macromolecule, term that may refer either to a crystal such as a diamond, in which the atoms are identical and held by covalent bonds (see chemical bond ) of equal strength, or to one of the units that compose a polymer .
..... Click the link for more information. were first studied in detail and their crystalline properties described. In the 1940s the process by which individual genes produce their unique products began to be understood as resulting from the different sequences of the base pairs that make up the genes. In the 1950s Linus Pauling Pauling, Linus Carl (pô`lĭng), 1901–94, American chemist, b. Portland, Oreg.
..... Click the link for more information. described the three-dimensional structure of proteins, and James Watson Watson, James Dewey, 1928–, American biologist and educator, b. Chicago, Ill., grad. Univ. of Chicago, 1947, Ph.D. Univ. of Indiana, 1950. With F. H. C.
..... Click the link for more information. and Francis Crick Crick, Francis Harry Compton, 1916–2004, English scientist, grad. University College, London, and Caius College, Cambridge. Crick was trained as a physicist, and from 1940 to 1947 he served as a scientist in the admiralty, where he designed circuitry for naval
..... Click the link for more information. described the double helix of the DNA molecule. Further advances were made in understanding DNA, protein, and virus synthesis and the regulation of genes, and by the 1970s, the techniques of genetic engineering genetic engineering, the use of various methods to manipulate the DNA (genetic material) of cells to change hereditary traits or produce biological products.
..... Click the link for more information. were enabling molecular biologists to study higher plants and animals, opening up the possibility of manipulating plant and animal genes to achieve greater agricultural productivity. Such techniques also opened the way for the development of gene therapy gene therapy, the use of genes and the techniques of genetic engineering in the treatment of a genetic disorder or chronic disease. There are many techniques of gene therapy, all of them still in experimental stages.
..... Click the link for more information. .

Bibliography

See A. Darbre, Introduction to Practical Molecular Biology (1988).

molecular biology

Field of science concerned with the chemical structures and processes of biological phenomena at the molecular level. Having developed out of the related fields of biochemistry, genetics, and biophysics, the discipline is particularly concerned with the study of proteins, nucleic acids, and enzymes. In the early 1950s, growing knowledge of the structure of proteins enabled the structure of DNA to be described. The discovery in the 1970s of certain types of enzymes that can cut and recombine segments of DNA (see recombination) in the chromosomes of certain bacteria made recombinant-DNA technology possible. Molecular biologists use that technology to isolate and modify specific genes (see genetic engineering).

molecular biology [mə′lek·yə·lərbī′äl·ə·jē]

(biology)

That part of biology which attempts to interpret biological events in terms of the physicochemical properties of molecules in a cell.

Molecular biology

The study of structural and functional properties of biological systems, pursued within the context of understanding the roles of the various molecules in living cells and the relationship between them. Molecular biology has its roots in biophysics, genetics, and biochemistry. A prime focus of the field has been the molecular basis of genetics, and with the demonstration in the mid-1940s that deoxyribonucleic acid (DNA) is the genetic material, emphasis has been on structure, organization, and regulation of genes. Initially, molecular biologists restricted their studies to bacterial and viral systems, largely because of their genetic and biochemical simplicity. Escherichia coli has been extensively examined because of its limited number of cellular functions and the corresponding restricted amount of genetic information encoded in the bacterial chromosome. Simple eukaryotic cells, such as protozoa and yeast, offer similar advantages and also have been studied. For these same reasons, bacteriophage and animal viruses have provided molecular biologists with the ability to study the structural and functional properties of molecules in intact cells. However, a series of conceptual and technological developments occurred rapidly during the late 1970s that permitted molecular biologists to approach a broad spectrum of plant and animal cells with experimental techniques. One of the major factors has been the development and applications of genetic engineering. Recombinant DNA technology allowed the isolation and selective modification of specific genes, thereby reducing both their structural and functional complexity and facilitating the study of gene expression in higher cells. The concepts and techniques used by molecular biologists have been rapidly and effectively employed to resolve numerous cellular, biological, and biochemical problems—becoming routine at both the basic and applied levels.

The recognition of DNA as the genetic material coupled with the discovery that genes reside in chromosomes resulted in an intensive effort to map genes to specific chromosomes. Initially genes were assigned to chromosomes on the basis of correlations between modifications in cellular function, particularly biochemical defects, and the addition, loss, or modification of specific chromosomes. See Chromosome aberration, Mutation

A major breakthrough was the development of somatic cell genetics. This is an approach in which, for example, human and hamster cells are fused, resulting in a hybrid cell initially containing the complement of human and hamster chromosomes. As the cells grow and divide in culture, the hamster chromosomes are retained while there is a progressive loss of human chromosomes. By correlating the loss of human biological or biochemical traits with the loss of specific human chromosomes, a number of human genes have been successfully mapped. See Somatic cell genetics

The development of methods for isolating genes and for determining the genetic sequences of the DNA in which the genes are encoded, led to rapid advances in gene mapping at several levels of resolution. Localization of specific genes to chromosomes is routinely carried out with cloned genes as probes. Further information about the segment of a chromosome in which a specific gene resides can be obtained by directly determining the DNA sequences of both the gene itself and the surrounding region.

Chromosome localization of specific genes has numerous applications at both the basic and clinical levels. At the basic level, knowledge of the positions of various genes provides insight into potentially functional relationships. At the clinical level, chromosome aberrations are now routinely used in prenatal diagnosis of an extensive series of human genetic disorders, and several chromosomal modifications have been linked to specific types of cancer. Knowledge of genetic defects at the molecular level has permitted the development of diagnostic procedures that in some instances, such as sickle cell anemia, are based on a single nucleotide change in the DNA.

Recombinant DNA

Recombinant DNA technology has provided molecular biology with an extremely powerful tool. In broad terms, applications of recombinant DNA technology can be divided into four areas—biomedical, basic biological, agricultural, and industrial. Biomedical applications include the elucidation of the cellular and molecular bases of a broad spectrum of diseases, as well as both diagnostic and therapeutic applications in clinical medicine.

In a strictly formal sense, the term recombinant DNA designates the joining or recombination of DNA segments. However, in practice, recombinant DNA has been applied to a series of molecular manipulations whereby segments of DNA are rearranged, added, deleted, or introduced into the genomes of other cells.

The ability to manipulate or “engineer” genetic sequences is based on several developments.

1. Methods for breaking and rejoining DNA. The precise breaking and rejoining of DNA has been made possible by the discovery of restriction endonucleases, enzymes that have the ability to recognize specific DNA sequences and to cleave the double helix precisely at these sites. Also important are the ability to join fragments of DNA together with the enzyme DNA ligase, and the techniques to determine the nucleotide sequence of genes and thereby confirm the identity and location of structural and regulatory sequences.

2. Carriers for genetic sequences. Bacterial plasmids, that is, circular double-stranded DNA molecules that replicate extrachromosomally, have been modified so that they can serve as efficient carriers for segments of DNA, complete genes, regions of genes, or sequences contained within several different genes. Bacteriophage and animal viruses, retroviruses, and bovine papilloma virus have also been successfully utilized as DNA carriers. These carriers are referred to as cloning vectors. Host cells in which vectors containing cloned genes can replicate range from bacteria to numerous other cells, including normal, transformed, and malignant human cells.

3. Introduction of recombinant DNA molecules. Genetic sequences in the form of isolated DNA fragments, or chromosomes, or of DNA molecules cloned in plasmid vectors can be introduced into host cells by a procedure referred to as transfection or DNA-mediated gene transfer—a technique that renders the cell membrane permeable by a brief treatment with calcium phosphate, thereby facilitating DNA uptake. Genes cloned in viruses can also be introduced by infection of host cells.

4. Selection of cells containing cloned sequences. Bacterial cells containing plasmids with cloned genes can be detected by selective resistance or sensitivity to antibiotics. In addition, the presence of introduced genes in bacterial, plant, or animal cells can be assayed by a procedure known as nucleic acid hybridization.

5. Amplification. Amplification of genetic sequences cloned in bacterial plasmids is efficiently achieved by treatment of host cells with antibiotics which suppress replication of the bacterial chromosome, yet do not interfere with replication of the plasmid with its cloned gene. Sequences cloned in bacterial or animal viruses are often amplified by virtue of the ability of the virus to replicate preferentially. See Gene amplification

6. Expression. Expression of cloned human genes can be mediated by regulatory sequences derived from the natural gene, from exogenous genes, or by host cell sequences.

Two clinically important genes, human insulin and human growth hormone, have been cloned and introduced into bacteria under conditions where biologically active hormones can be produced.

Progress has been made in applications of recombinant DNA technology to the resolution of agricultural problems, especially for the improvement of both crops and livestock. See Adenohypophysis hormone, Breeding (animal), Breeding (plant), Genetic engineering, Insulin

Biophysical analysis

Understanding of the structural properties of molecules and the interaction between molecules that constitute biologically important complexes has been facilitated by biophysical analysis. For example, developments in the resolution offered by techniques such as electron microscopy, x-ray diffraction, and neutron scattering have provided valuable insight into the structure of chromatin, the protein-DNA complex which constitutes the genome of eukaryotic cells. These techniques have also provided clues about modifications in chromatin structure that accompany functional changes. One possible application of biophysical analysis is the diagnosis of human disorders by adaptation of nuclear magnetic resonance for tissue and whole body evaluation of soft tissue tumors, blood flow, and cardiac function.

Flow of molecular information

Information for all cellular activities is encoded in DNA; selective elaboration of this information is prerequisite to meeting both structural and biochemical requirements of the cell. In this regard, there are three major areas of investigations by molecular biologists: (1) the composition, structure, and organization of chromatin, the protein-DNA molecular complex in which genetic information is encoded and packaged; (2) the molecular events associated with the expression of genetically encoded information so that specific cellular biochemical requirements can be met; and (3) the molecular signals that trigger the expression of specific genes and the types of communication and feedback operative to monitor and mediate gene control. See Chromosome, Deoxyribonucleic acid (DNA), Gene, Genetic code, Nucleic acid