Synthetic biology

Synthetic biology

Interdisciplinary branch of biology and engineering, applying multiple disciplines to build artificial biological systems for research, engineering, and medical applications.

Synthetic biology is the design and engineering of biologically based parts, novel devices and systems as well as the redesign of existing, natural biological systems. It has the potential to deliver important new applications and improve existing industrial processes, as it is applied to challenges in healthcare, agriculture, manufacturing and environmental protection and remediation. As a multidisciplinary field, synthetic biology brings together social scientists, biologists, chemists, engineers, mathematicians, and others to identify major challenges in society and collectively find solutions. Goals of synthetic biology include generating organisms that produce a substance such as medicine, agricultural products or fuel, metabolize pollutants, have the ability to sense something in the environment. Other applications include the generation of disease-resistant crops, tissue engineering and the building of engineered living materials that self-assemble or modulate the performance of a material. Please see Cluster: Synthetic biology for a collection of topics, tools, applications, organizations and companies related to synthetic biology.

Synthetic biology is not only an applied discipline but also a fundamental discipline. For example, the construction of the minimal bacterial genome, the synthetic yeast project and parts of the Genome Project-write initiative do not have direct applications but aim to advance our knowledge of genomes. The synthetic biology community has a mindset that is influenced by the phrase by theoretical physicist Richard Feynman, “What I cannot create, I do not understand”. The concept is that using fundamental principles it should be possible to build up or understand an idea, proof or concept from the ground up. The idea of understanding by synthesis is a major theme in synthetic biology. Synthetic approaches have not been used in biology to the extent they have been used in other disciplines, such as gaining an understanding of the laws of chemistry through chemical synthesis.

Synthetic biology uses two main working directions for the construction of artificial biological systems with tailored properties: The top-down approach and the bottom-up approach. The top-down approach starts from existing micro-organisms and the genome is manipulated and reduced based on acquired knowledge to achieve a desired property. The bottom-up approach begins at the molecular level from functional biological devices like genome, transcriptome, proteome, metabolome, and aims to assemble these biological parts into an artificial cell or synthetic cell. A biodesign platform being developed in synthetic biology uses design-build-test-iterate (or deploy) to create cells or organisms that produce novel materials or to create organisms that perform novel functions.

Similar tools are used in genetic engineering, genome editing and synthetic biology and a line is sometimes drawn between synthetic biology and the former disciplines by the much larger scale of the manipulations being performed in synthetic biology. Enhancing photosynthesis and growth of plants is a research area that used both genetic engineering and synthetic biology. Many biological building blocks are interchangeable between cyanobacteria, algae and plants and swapping homologous photosynthetic proteins between species would be genetic engineering. Synthetic biology approaches would involve the exchange of entire multiprotein complexes between distantly related species. Synthetic biology involves building using standardized genetic parts and synthetic biological circuit design.

Some governments have expressed concerns that synthetic biology could increase the number of agents of concern such as chemical and biological threats and require the development of detection, identification and monitoring systems as countermeasures.

History

Biophysicist Stéphane Leduc coined the term synthetic biology and laid out the philosophical and experimental foundations in 1912. Leduc argued that no boundary separates life from physical phenomena, illustrating this by growing chemical gardens of inorganic crystals that resemble living systems. The theoretical basis of contemporary synthetic biology is largely attributed to Waclaw Szybalski,’s statements in 1974 related to the invention recombinant DNA technology.

Up to now we are working on the descriptive phase of molecular biology. … But the real challenge will start when we enter the synthetic biology phase of research in our field. We will then devise new control elements and add these new modules to the existing genomes or build up wholly new genomes. This would be a field with unlimited expansion potential and hardly any limitations to building ‘new better control circuits’ and … finally other ‘synthetic’ organisms …

Rather than a biophysical discipline, contemporary synthetic biology is largely an engineering discipline that emphasizes principles such as standardization, modularity, digital logic and mathematically predictable behavior. Synthetic biology as an engineering discipline began being discussed around 2005-2006. A possible hierarchy for synthetic biology inspired by computer engineering, was described by researchers at Princeton University. DNA, RNA, proteins and metabolites are analogous to the physical layer of transistors, capacitors and resistors. Biochemical reactions that regulate the flow of information and manipulate physical process are analogous to the device layer with logic gates. It is envisioned that synthetic biologist would assemble biological devices into pathways that function like integrated circuits.

Drew Endy, a civil engineer, and fellow researchers at MIT are recognized at major contributors to synthetic biology and brought forth the BioBricks Foundation dedicated to developing the approach of using the engineering mindset of standardized interchangeable biological parts. Endy and his colleagues also laid the groundwork for the international Genetically Engineered Machines Competition (iGEM), which began as an MIT summer course in 2003. Jay Keasling at University of California, Berkeley contributed to the framing of synthetic biology as a new engineering discipline by engineering yeast to produce artemisinin, used in malaria drugs in 2006. Another contributor to the synthetic biology field is Craig Venter with his work deconstructing micro-organisms in order to find the minimal amount of genetic material needed for a living cell and building a fully synthetic genome.

Timeline

January 1, 2000

Genetic toggle switch and repressilator papers

An article published in Nature reports the first genetic circuits had been engineered to carry out designed functions using a genetic toggle switch. Cells that harbored the circuit could toggle between two stable expression states in response to external signals.

With the repressilator, activation of an oscillatory circuit resulted in the ordered, periodic oscillation or repressor protein expression.

These studies combined quantitative design, physical construction, experimental measurement, and hypothesis-driven debugging to construct synthetic circuits, which became a characteristic feature of constructing synthetic circuits.

November 1, 1978

Nobel Prize in Physiology or Medicine for the discovery of restriction enzymes

Werner Arber, Daniel Nathans, and Hamilton Smith share the 1978 Nobel Prize "for the discovery of restriction enzymes and their application to problems of molecular genetics." A November 1978 editorial in Gene states, "The work on restriction nucleases not only permits us easily to construct recombinant DNA molecules and to analyze individual genes but also has led us into the new era of 'synthetic biology' where not only existing genes are described and analyzed but also new gene arrangements can be constructed and evaluated.

June 29, 1912

The term synthetic biology was coined by French biophysicist Stéphane Leduc

People

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Further reading

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Documentaries, videos and podcasts

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Companies

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Ginkgo Bioworks

Jason Kelly

Boston, Massachusetts, USA

Design custom microbes

References

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