Synthetic Biology Resources
From DrugPedia: A Wikipedia for Drug discovery
Definition of Synthetic Biology
Synthetic biology (also known as Synbio, Synthetic Genomics, Constructive Biology, Extreme Genetic Engineering or Systems Biology) – the design and construction of new biological parts, devices and systems that do not exist in the natural world and also the redesign of existing biological systems to perform specific tasks. Advances in nanoscale technologies – manipulation of matter at the level of atoms and molecules – are contributing to advances in synthetic biology.
Basics of SynBio
At the core of synthetic biology is a belief that all the parts of life can be made synthetically (that is, by chemistry), engineered and assembled to produce working organisms. DNA code is regarded as the software that instructs life, while the cell membrane and all the biological machinery inside the cell are regarded as the hardware (or wetware as it is sometimes known) that need to be snapped together to make a living organism.
DNA synthesis reduces the time it takes genetic engineers to isolate and transfer DNA in order to build genetically modified organisms.
“We’re going to build you exactly what you are looking for: Whole plasmids, whole genes, gene fragments . . . and in one to two years, possibly a whole genome.” – John Mulligan CEO of Blue Heron Biotechnology, Washington (USA)
“There is no technical barrier to synthesizing plants and animals, it will happen as soon as anyone pays for it.” — Drew Endy, MIT
Drew Endy of MIT speculates that within 20 years human genomes will be synthesised from scratch.
At present Craig Venter holds the world’s gene-speed record for synthetically producing a 5,386 bp genome (of the virus phiX 174) in under 14 days (although there were errors in his copy).
Synthetic biologists want to work below the level of the gene, at the level of the codon – to identify codons and rearrange them to build new sets of biological instructions. Because there are 64 possible codons (four bases linked together in sets of three, or 4*4*4) but only 20 different amino acids they translate into, synthetic biologists can choose among different options for codons when they want to express a specific amino acid (known as codon optimization). It may be that one codon works better in bacteria and another in plants even though both produce the same amino acid.
Some synthetic biologists take the approach of combing through the genetic code of existing organisms and removing or reducing unnecessary codons to get a sleeker version of the genetic code. Others, by combining codons into stand-alone programming instructions, are developing “standard parts” analogous to the standard parts of electronic circuitry or the standard commands of a computer language. They keep an inventory of these standard parts, and are making them available for others to assemble into more complex genetic systems. Others are designing entirely new artificial amino acids that result from codon combinations not found in nature.
In the US and Europe some synthetic biologists hope to build an artificial “protocell” that will contain and express synthetic DNA as flexibly as a computer stores document files and runs computer programmes.
Unfortunately for would be life builders, genetic code is not as linear as computer code. While the popular view of genetics links units of DNA (genes) to specific traits, the reality is messier. In real life, genes and parts of genes co-operate in subtle and complex networks, each producing proteins that promote or suppress the behaviour of other genes. The result is a system of cellular regulation that controls the amount or timing by which a substance or trait is produced – a bit like electronic circuits that regulate electrical current.
Geneticists interested in manipulating genomes have begun mapping the interactions between genes to try to determine the full set of interactions necessary to produce a desired protein. They can represent these networks with circuit diagrams similar to those used in electronics. The set of interactions that involve a network of DNA molecules acting together to produce a protein can be referred to as a “genetic pathway” and synthetic biologists are now trying to rebuild or alter these genetic pathways as discreet sections of the genome. This involves designing not just one coding region of DNA, but several different areas of code, and then putting them together as a synthetic chromosome. By altering these networks and pathways, synthetic biologists can increase the production of a protein or stimulate the production of an entirely different substance, such as a plastic or a drug.
An Introduction to Five Major Areas of Research in Synthetic Biology
1. Making Minimal Microbes – Post-modern Genomics
In 1995 Venter announced that he was first to sequence the entire genome of a living organism (the bacterium known as Hemophilus influenzae). In 2003 Venter made headlines when his team created the first synthetic virus from scratch – and it took them only 14 days to do it. Venter is notorious for pushing the boundaries on the commercial exploitation of life. His newest commercial venture, Synthetic Genomics, Inc., founded in 2005 with $30 million in venture capital, aims to commercialise a range of synthetic biology applications, starting with energy production. He was also demostrated in Minimal Genome Project (1990) in Mycoplasma genitalium that the bacterium might be able to survive with almost half its genes removed. Others are now trying to minimise the genome of organisms such as E. coli.
Venter calls Mycoplasma laboratorium a “synthetic chromosome” and his intention is to use it as a flexible biofactory into which custom-designed synthetic “gene-cassettes” of four to seven genes can be inserted, genetically programming the organism to carry out specific functions. As a first application, Venter hopes to develop a microbe that would help in the production of either ethanol or hydrogen for fuel production (See the New Synthetic Energy Agenda ). He is also looking to harness the mechanisms of photosynthesis to more effectively sequester carbon dioxide, ostensibly as a means of slowing climate change. Venter talks big. In 2004 he predicted that “engineered cells and lifeforms [will be] relatively common within a decade.”
2. Assembly-Line DNA – “Lego” Life-forms to Order
Drew Endy (MIT), an engineer by training, is also a computer programmer and he and those around him use computer and electronics metaphors to describe synthetic biology: A living organism is a ‘computer’ or ‘machine’ made up of genetic ‘circuits’ in which DNA is the ‘software’ that can be ‘hacked.’ He points out that, “Biological engineers of the future will start with their laptops, not in the laboratory. Let’s build new biological systems – systems that are easier to understand because we made them that way.” Endy longs for a logical and predictable biotechnology, what he and others refer to as “intentional biology.” “We would like to be able to routinely assemble systems from pieces that are well described and well behaved,” Endy explains.
The BioBrick Foundation - To do this he and his colleague at MIT, artificial intelligence pioneer Tom Knight, have invented several hundred discrete DNA modules that behave a little like electronic components. They include sequences that turn genes off and on, transmit signals between cells or change colours between red, green, yellow and blue. Knight and Endy then encourage others to combine those modules into more complex genetic circuits. They call these modules Biobricks or “standard parts” and their non-profit BioBricks Foundation maintains over 2000 BioBricks in its registry of standard parts that can be freely used by other synthetic biology researchers. Each of these BioBricks is a strand of DNA designed to reliably perform one function and to be easily compatible with other BioBricks in making longer circuits. The completed circuits are then dropped into E. coli, yeast or another microbial host to see if they function.
Every year Endy, Knight and their fellow synthetic biologists at MIT convene an International Genetically Engineered Machine Competition (known as iGEM).
3. Building Artificial Cells from the Bottom Up – Ersatz Evolution
4. Pathway Engineering – Bug Sweatshops
5. Expanding Earth’s Genetic System – Alien Genetics
