Sunday, 20 March 2022

A new direction in science is synthetic biology.

     The term "synthetic biology" was first used in 1980 by Barbara Hobom to describe a bacterium that had been genetically modified using recombinant DNA technology[1].

    The term was then proposed again in 2000 by Eric Kool and other speakers at the American Chemical Society's annual meeting in San Francisco. It was used to describe the synthesis of artificial organic molecules that play a certain role in living systems [1].

    Synthetic biology is a new field of biology whose goal is to design and create new biological systems not found in nature. It deals with adding to the properties already available in the body, for example, bacteria, new properties or modifying existing ones. In the future, it is planned to create separate organisms capable of independent existence and reproduction with strictly specified properties.

    The main goals of synthetic biology are three:

    Learn more about life by building it from atoms and molecules, rather than taking it apart, as was done before.

    To make genetic engineering worthy of its name is to transform it from an art into a rigorous discipline that is constantly evolving, standardizing previous artificial creations and recombining them to make new, more complex living systems that did not exist before in naturе. Erase the boundary between the living and machines in order to arrive at truly programmable organisms.

    Consider the possibilities of synthetic biology for various disciplines. First, biologists will be able to better understand natural biological systems (it is worth remembering the words of Richard Feynman: “What I cannot create, I do not understand” 

    Secondly, for chemists, synthetic biology can be seen as the next logically necessary step in synthetic chemistry (synthesis of drugs, new materials, development of more advanced methods of analysis).

    Synthetic biology begins its history in 1989, when a team of biologists from Zurich (headed by Steven Benner) synthesized DNA containing two artificial nucleotide pairs, in addition to the four known ones used by all living organisms on Earth (adenine, guanine, cytosine, thymine - DNA, in RNA - cytosine is replaced by uracil) (Fig. 1).

    Biologist Drew Andy ( Massachusetts Institute of Technology) is working on the creation of a bio-detector of hidden mines (Fig. 2): the desired genetic code is introduced into the bacteria, then the bacteria are sprayed on the ground. Where there is TNT in the soil (and it inevitably seeps out of the mine), bacteria synthesize a fluorescent protein (Fig. 3) [6], after which mines can be detected in the dark [4].

    The next step in the field of synthetic biology was taken by a group of scientists from Princeton University , which created luminous bacteria. And biologists from the University of Boston  endowed this bacterium with an elementary digital binary memory. They connected two new genes in bacteria that are activated in antiphase - depending on the chemical components at the input, these bacteria “switched” between two stable states, like a trigger on transistors.
    But in order to create a luminous E. coli bacterium that could be turned on and off like a light bulb, the above work is not enough. Although both necessary components have already been created in two different organisms. Therefore, Andy is now actively working on the creation of a mechanism, infrastructure, or, if you like, science that would make it possible to systematize such work, to bring them into a system.

    Then it will be possible to design living systems that behave in a predictable way and use interchangeable parts from the standard set of life bricks.
    In the fall of 2003, a group of scientists from the American Institute for Biological Energy Alternatives assembled a live phiX174 bacteriophage virus in just two weeks, synthesizing its DNA - 5 thousand 386 nucleotide pairs. The synthesized virus is similar in behavior to natural viruses[4]. And a group of scientists from MIT dismantled another bacteriophage virus into parts (Fig. 4).

    Craig Venter, head of the Venter Institute - JCVI, is one of the most prominent proponents of synthetic biology. He intends to obtain a simple basic organism, on which in the future it is possible to test the work of a wide variety of artificial or borrowed genes. Moreover, in this universal code there are pieces from different organisms, selected in such a way as to ensure the basic functions of the cell, including growth and reproduction. Such a "minimal" organism would provide ideal conditions for experiments with genes, since it would not contain anything superfluous. A group of JCVI scientists have filed a US patent for the "minimal bacterial genome" that is sufficient to sustain the life of a single-celled organism, and applied for a similar international patent, which lists more than 100 countries in which it must protect the Institute's rights to this code.

    Steen Rasmussen, together with colleagues from the American National Laboratory at Los Alamos, intends to create a fundamentally new form of life. Chemists and physicists intend to create a protocell, which, even though it will be more primitive than a bacterium, will have to have the main features of life: produce its own energy, give offspring and even develop. These searches may provide an answer to the question of whether the emergence of life is an accident or inevitability. The protocell, according to the author's idea, should be the simplest living system: fatty acids, some surfactant and an artificial nucleic acid PNA (PNA, peptide nucleic acid).
    Stephen Benner of the US Foundation for Applied Molecular Evolution is one of the pioneers of synthetic biology. In early 2009, he released the book Life, the Universe and the Scientific Method, in which he expressed his point of view on how modern scientists are trying to understand the origin of life and thereby imagine what life could be like on other worlds.
    The revolutionary breakthrough occurred on May 20, 2010.

    This day will forever go down in history as the day on which the creation of the first replicable living cell based on a synthesized genome was announced.

    They created an artificial living organism at the Craig Venter Institute (J. Craig Venter) under the guidance of Craig Venter himself. In total, the research that led to the creation of the first synthetic organism capable of reproduction took more than 15 years, but this event carries a revolutionary potential for science and, perhaps, will allow humanity to solve the most ambitious tasks, such as new sources of food raw materials, medicines and vaccines , the victory over environmental pollution, the synthesis of clean water, etc.

    Currently, more than 100 laboratories around the world are engaged in synthetic biology [4]. One of the leaders in this field is the biologist Drew Andy (Fig. 6) from the Massachusetts Institute of Technology, who is organizing work in this area. The systematization of work in this area will make it possible to design organisms with desired properties using interchangeable "details" from a standard set of genes. Scientists strive to create an extensive genetic bank that allows you to create any desired organism (similar to the creation of an electronic circuit from industrial transistors and diodes). The bank is made up of biobricks - DNA fragments, whose function is strictly defined and which can be introduced into the cell genome for the synthesis of a known protein. All selected biobricks are designed to interact well with all others on two levels[4]:
   mechanical - so that they can be easily manufactured, stored and included in the genetic chain;
software - so that each brick sends certain chemical signals and interacts with other code fragments

    Now more than 140 biobricks have been created and systematized at the Massachusetts Institute of Technology (Fig. 6). The difficulty lies in the fact that many engineered DNA fragments, when introduced into the genetic code of the recipient cell, destroy it.

    Synthetic biology is able to create genetically engineered bacteria that can produce the most complex and scarce drugs cheaply and in industrial volumes. Engineered genomes could lead to alternative energy sources (biofuel synthesis) or bacteria to help remove excess carbon dioxide from the atmosphere. 
    

    

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