Introduction to synthetic biology
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Synthetic biology is a field that aims to design and engineer biological organisms and systems for useful purposes. It involves modifying organisms to have new abilities by redesigning their DNA. Some key goals of synthetic biology include producing medicines, manufacturing chemicals, and solving environmental problems in eco-friendly ways. It differs from genetic engineering in aiming to make more extensive and predictable changes at a larger scale, such as designing whole new genomes. Synthetic biologists use techniques like DNA synthesis and standardization to achieve their goals. Recent advances include using synthetic biology to sense environmental conditions, produce chemicals, and even create artificial enzymes not found in nature.
Introduction to synthetic biology
- 1. MBB-591 Presented by – Samrity Sharma (H-2018-56-M)
- 2. Outline • What is synthetic biology? • Why synthetic biology? • Aims of synthetic biology and how it is different from genetic engineering? • Approach • Principles • Synthesis of DNA artificially. • Popular issues.
- 3. Introduction Biotechnology has become a major supporting technology in the 20th century. A relative recent development within biotechnology is the emergence of the field of synthetic biology. Biotechnology is a broad term encompassing the application of biological components or processes to advance human purposes whereas Synthetic biology refers to a set of concepts, approaches, and tools within biotechnology that enable the modification or creation of biological organisms.
- 4. • Although academic interest in synthetic biology has gained significantly over the past decade (Oldham, Hall, & Burton, 2012), scientists have been debating over its meaning for over a century. • In the past 100 years, synthetic biology was used in both conceptual and practice orientated discussions, describing in various degrees to what extent biological systems could be exploited.
- 5. History in brief. • In 1912, both Stéphane Leduc (Leduc,1912) and Jacques Loeb (Loeb, 1912) mentioned synthetic biology in speculations over possibilities to create artificial living systems. • Later on, in 1974, Waclaw Syzbalsky mentioned synthetic biology to describe the application of recombinant DNA technology to generate organisms with new genetic properties (Benner, 2010). • Around a decade ago, the concept started to be used to refer to the synthesis of unnatural molecules (Rawls, 2000)(Sismour & Benner, 2005), unnatural chemical systems (Benner & Sismour, 2005), biology-inspired systems (Pleiss, 2006), and functions not existing in nature (Serrano, 2007). • The first artificial cells were developed by Thomas Chang at McGill University in the 1960s. These cells consisted of ultrathin membranes of nylon, collodion or crosslinked protein whose semipermeable properties allowed diffusion of small molecules in and out of the cell. These cells were micron-sized and contained cell, enzymes, hemoglobin, magnetic materials, adsorbents and proteins.
- 6. Semi-synthetic drug artemisinin. In 2003, Jay Keasling and his team at UC Berkeley announced success story of synthetic biology. They had successfully implanted genes into yeast that produces a precursor to the antimalarial drug artemisinin. Though the disease can be treated with antimalarial drugs, there is limited access to medical care in the poorest of the affected regions They use synthetic biology to develop strains of Saccharomyces cerevisiae (baker's yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin.
- 7. ARTIFICIAL CELL. • Daniel Gibson at the J. Craig Venter Institute in Rockland, Maryland, and his colleagues in 2010 began with a highly accurate genome sequence they had made of the bacterium Mycoplasma mycoides. • Using this as a template, they ordered a set of short DNA strands called 'cassettes', each about 1,000 base pairs long, from a DNA-sequencing company, then inserted the cassettes into a yeast cell, where the yeast's own genetic machinery strung them together into a copy of the natural M. mycoides genome. • Finally, the researchers transplanted the 1.1-million-base-pair-long synthetic genome into cells of a closely related bacterial species, Mycoplasma capricolum. Although only the genome of the new cell was custom-built, the researchers refer to the entire cell as "synthetic" because its molecular contents quickly took on the characteristics of M. mycoides. "By changing the chromosome in the cell, it completely changes the cell from one form to another," Venter said in a press briefing .
- 9. What is Synthetic Biology? Synthetic biology is a field of science that involves redesigning organisms for useful purposes by engineering them to have new abilities. Synthetic biology researchers and companies around the world are harnessing the power of nature to solve problems in medicine, manufacturing and agriculture.
- 10. Synthetic biology (SynBio) is an interdisciplinary branch of biology and engineering. Decreasing costs of DNA synthesis and recent advances in technology have fueled the success of synthetic biology companies in recent years, and now comprises one of the fastest growing and most funded areas of commercial biotechnology.
- 13. COMPANIES PRODUCING SYNTHETIC DNA
- 14. Why synthetic biology ? Cells can make copies of themselves : Many of the challenges that synthetic biologists are targeting can be addressed by other engineering disciplines, such as electrical, chemical, or mechanical engineering, but synthetic biology’s solutions offer a few unique advantages as cars can’t copy themselves it needs a factory to build a car. Also, some organisms can copy themselves incredibly quickly, even with minimal nutrients. For example, in the lab, the bacterium E. coli can replicate and divide in about 30 minutes. Therefore, synthetic biology is an attractive approach for producing large amounts of a specific product because we can grow a programmed cell relatively easily to meet large-scale production demands.
- 15. Cells contain the biological machinery to carry out many complex tasks— specific chemical reactions, for example—that would be difficult, if not impossible, to accomplish otherwise. And, they do so with nanoscale precision that is difficult to replicate in any traditional fabrication facility. Also, when their nanoscale machinery breaks, cells have mechanisms to repair themselves, at least to some extent, which puts them at a great advantage over more typical factory-based production processes. Cellular complexity introduces its own hurdles to be considered, as well, but its potential utility is enormous. Synthetic biology has the potential to produce eco-friendly solutions to many difficult problems. By necessity, the byproducts of synthetic biology applications are generally nontoxic, because most toxic compounds would kill the very cells that are doing the work. In addition, harnessing natural cellular systems often results in economical processes. Today’s industrial production of compounds consume large quantities of energy, often creating significant amounts of environmentally harmful waste and frequently requiring high temperatures or pressures.
- 16. Beyond its usefulness for addressing real-world challenges, synthetic biology is also a fantastic approach to learn more about the workings of natural systems. As researchers dissect increasingly complex cellular functions, they can use synthetic biology to test their hypotheses from additional angles. For example, if their biochemical research results suggest that a certain protein acts as a sort of on/off switch, they can test this result by replacing the existing protein with a protein that is known to exhibit on/off behavior. If the new synthetic system and the natural system behave similarly, the result provides further evidence that the natural protein acts as the researchers suspected.
- 17. Aims of synthetic biology The goal of synthetic biology. Synthetic biologyaims to write DNA (left) that instructs a cellor organism(right)to behaveaccording to design specifications. • At the most basic level, synthetic biology aims to engineer living cells to do something useful like treat a disease, sense a toxic compound in the environment, or produce a valuable drug. • As Figure suggests, synthetic biologists achieve these outcomes by altering an organism’s DNA so that it behaves “according to specification”. • Craig Venter, for instance, is working to develop bioreactors in which algae cells convert carbon dioxide from the atmosphere into fuel.
- 18. Synthetic biology today. Currently, synthetic biologists generally design a portion of DNA (left) and combine it with an existing cell or organism (middle) so that the new cell or organism (right) behaves according to design specifications. • We can think of cells as complex miniature factories, hence by employing cells to produce or synthesize a particular product we can make it a more eco friendly process . • DNA provides instructions to make all the machines in the factory — proteins, nucleic acids, multicomponent macromolecular complexes, and more. These “machines” then carry out the work of the cell. The organism’s naturally occurring DNA allows the cell to meet its basic survival and reproductive needs. Synthetic biologists can change a cell’s DNA so that the cell takes on new, useful functions.
- 19. • An illustrative—example of synthetic biology’s potential scale is the genetic reprogramming of a tree so that it will grow into a fully functional house based on the genetic instructions designed by a synthetic biologist. Such a system would take advantage of the tree’s natural program (to grow by taking in a few nutrients from the environment) and put it to use for society’s needs. Genetically programming a tree to grow into a house, however, is far beyond the scale of traditional genetic engineering as well as the capacity of synthetic biology at this point.
- 20. Difference between synthetic biology and genetic engineering. 1. Synthetic biology and genetic engineering differ in the scale at which they aim to make changes. 2. Genetic engineers are usually introducing one or two small changes to investigate a specific system, whereas synthetic biologists aim to design new genomes and redesign existing genomes at a grand scale
- 21. Genetic engineering. • Genetic engineering includes recombinant DNA technologies and molecular cloning (Abdullah et al., 2014). With modern genetic engineering, it is possible to recombine, cut and paste genes from one organism into another target organism. Synthetic Biology • The application of various scientific and intellectual areas to design and create full genetic systems that can be implemented in an organism in order to perform a self-regulated task. This does not imply just recombining DNA, but designing and modeling a novel pathway by assembling many different pieces of genetic material collected and characterized from natural organisms.
- 22. “now a powerful form of genetic engineering could revolutionize the production of some of the most sought after flavors and fragrances” ( 21 October 2013, The New York Times) More purpose driven science “Synthetic biology aims to allow more extensive changes , and in a more efficient and predictable way” ( 5 September 2010, The New York Times) Allows for more predictability “this also entailed building the bacteria itself-redesigning a living organism, using the tools of a radical new realm of genetic engineering called synthetic biology” (14 Feb 2010, The New York Times Creates new organisms instead of simply relying on tinkering with naturally occurring ones
- 23. Fundamental approach • Synthetic DNA synthesis.
- 24. The Synthetic Biology Toolkit Molecular biologists have spent years developing methods to manipulate DNA in different ways. Following are three of the most crucial and well-established techniques, which are used extensively in synthetic biology: • Reading the DNA code • Copying existing DNA sequences • Inserting specific DNA sequences into existing DNA strands Tool Molecular biology technique Natural cellular process Reading DNA Sequencing DNA replication Copying DNA PCR DNA replication Inserting DNA rDNA with restriction enzymes and ligases Defense from infection, DNA recombination and repair The molecular biologytoolkit and its natural origins
- 25. The Tools Expanded for Synthetic Biology • Although methods used in molecular biology have been around for many years and have been used to great effect in research, they are not sufficient for synthetic biology. They might be sufficient to insert a gene from a chameleon into a plant, for example, but they would not enable the reliable reprogramming of a plant to grow into a house. • Consequently, we use the term genetic engineering, not synthetic biology, to refer to the relatively small-scale manipulation of genes in a host organism, perhaps altering at most a handful of genes.
- 26. To achieve more ambitious engineering goals, synthetic biologists expand their toolkit beyond that of traditional genetic engineering to also include design principles from the more established engineering disciplines • Theseadditional tools, which are still largelyin development, include: • standardization, abstraction > Bothstandardization and abstraction are directly drawnfromthe toolkits of other engineering disciplines, whereas DNA synthesis is an engineering tool unique to syntheticbiology.
- 27. Standardization • Standardization is a key attribute of mature engineering disciplines because it makes it possible for engineers to more quickly implement exciting, innovative, and useful solutions. • Standardization is a crucial part of any engineering discipline because it facilitates designers being able to reuse parts, combine efforts with other teams, and work efficiently. • For synthetic biologists, standardization enables small pieces of DNA to be physically and functionally connected.
- 28. Standardization
- 29. Abstraction • Through abstraction, synthetic biologists can design complex parts, devices, and systems without worrying about every detail of how they work. Instead, the focus is on the end goal, which is the final system output or behavior. • Abstraction is an important aspect . It allows us to think about and communicate our plans without becoming bogged down in the details all at once. • Some useful abstraction levels for designing a new synthetic organism includes: systems, devices, parts, and DNA. • It is the enumeration of many biological parts, as well as the reliable composition of these parts.
- 30. DNA synthesis • Synthetic biologists are often designing new sequences for which no template exists. When there is no template strand to follow, they determine the nucleotide order of the synthetic DNA by using digital sequence information. With this technology, synthetic biologists can write new DNA sequences that have never been written before.
- 31. Recent Advaces of synthetic biology • Sensing environmental conditions: e.g. ecosystem contaminants, metabolic conditions or explosives. • Combat infections or delivery at Nano-scale level • Contributing in production of existing and novel bio based chemicals and products: e.g. production of chemicals. • The synthetic biology initiative known as Human Genome Project-write (HGP-write), rallying scientists to build entire human chromosomes (Boeke et al.,2016). • System biology. • Minimal cells.
- 32. World’s first artificial enzymes created using synthetic biology: Professor Philipp Holliger’s (MRC Laboratory of Molecular Biology, Cambridge) team have created the world’s first enzymes – ‘XNAzymes’ – made from artificial genetic material not found anywhere in nature. This was published on 01 Dec 2014 Because this XNAzymes are much more stable than naturally occurring enzymes, this synthetic biology approach could provide a starting point for an entirely new generation of drugs and diagnostics for a range of diseases, particularly useful in developing new therapies against cancers and viral infections which exploit the body’s natural processes to take hold in the body.
- 33. Enzymatic Menthol Production(January 2018) Menthol isomers are high-value commodity chemicals, produced naturally by mint plants. The high demand by the flavor and fragrance industries for natural sources has a high cost in terms of arable land use and expensive distillation and filtration processes, which means that alternative clean biosynthetic routes to these compounds are commercially attractive. Researchers at the University of Manchester have engineered E. coli to efficiently convert pulegone (an essential oil produced by a variety of plants) to menthol. They demonstrated that ketosteroid isomerase (KSI) from Pseudomonas putida can act as an IPGI Using a robotics-driven semi rational design strategy KSI variant was demonstrated to function efficiently within cascade biocatalytic reactions with Mentha enzymes pulegone reductase and (−)-menthone:(−)-menthol
- 34. Caffeine-Triggered Cells Help Control Blood Sugar in Diabetic Mice Scientists engineered human cells to produce a molecule that stimulates insulin secretion in the presence of caffeine. • Scientists have engineered human cells that boost the production of insulin in response to caffeine. These modified cells could one day help treat patients with type 2 diabetes • Martin Fussenegger, a biotechnologist at the Swiss Federal Institute of Technology in Zurich and his colleagues engineered human embryonic kidney cells that produce a synthetic version of human glucagon-like peptide a molecule that prompts the release of insulin, in the presence of caffeine. • Then, the team injected diabetic mice with an implant containing hundreds of the engineered cells. This revealed that the animals’ blood-sugar levels could be controlled by simply adding a caffeinated beverage, such as coffee, cola, or Red Bull, to their meals. Non caffeinated beverages, such as herbal tea and chocolate milkshakes, had no effect. Jun 20, 2018 - DIANA KWON
- 36. Researchers Build a Cancer Immunotherapy Without Immune Cells A team has engineered two stem cell lines into “synthetic T cells” that destroy breast cancer cells in vitro. Nov 13, 2017 - ABBY OLENA • Typical immunotherapies work by harnessing the power of immune system. In CAR –T cell therapy for example patients receive a transfusion of their own T cell that have been modified to recognize a specific protein on the surface of cancer cells and then destroy the cancer but as we reprogram the immune system it is having some harmful risks to cause effects. • To engineer a similar therapeutic using other type of cells, researchers built a cancer detecting sensor in : • HEK-293 T cell : a common cell line derived from human embryonic kidney cells. • Human mesenchymal stem cells. • Sensor is in two parts i.e. antenna and receptor which not only destroys the cancerous cells but also kills those cells in the immediate vicinity of cancer cells.
- 37. Synthetic Stem Cells Regenerate Heart Tissue in Mice These engineered “cells” were made from the secretions and membranes of human mesenchymal stem cells. Jun 1, 2017 DIANA KWON • Mesenchymal stem cells have been tested in various clinical trials as they can promote regeneration when injected into a tissue but there was a major limitation • These MSC cells need to be carefully frozen to keep them alive in storage, then defrosted, expanded and gently maintained until used . • This process is very tedious and sometimes can affect the potency of the cell .
- 38. CELL TYPE MODE OF DELIVERY VIABILITY APPROXIMATE SIZE TESTED IN Synthetic mesenchymal stem cells Must be injected directly into site of action (e.g., heart) At least one week at room temperature 20 μm Mice Mesenchymal stem cells derived from humans or other animals Can be injected into blood vessels, because they will migrate to the site of injury Around 24 hours at room temperature 20 μm Humans, in multiple clinical trials To overcome this problem researchers engineered synthetic MSCs which were built from human MSC secretions packaged in a biodegradable micro particle and then coated with MSC membranes . These synthetic MSC cells withstood harsh cryopreservation and lyophilization without loosing its properties.
- 39. • Uncontrolled Release : A number of measures are being proposed or adopted to ensure adequate biological control, including: engineering bacteria to be dependent on nutrients with limited availability; and integration of self-destruct mechanisms that are triggered should the population density become too great. • Bioterrorism : A number of proposals have been made by both scientific groups and government agencies to address the dual use (military/civilian) nature of synthetic genomics, including: controls over commercial DNA synthesis and public research; and considering the impact of synthetic biology on international bioweapons conventions. As yet there is no policy consensus on these issues. • Creating Artificial Life :One of the most potent promises of synthetic biology is the creation of ‘artificial life’. This has provoked fears about scientists ‘playing God’ and raises philosophical and religious concerns about the nature of life and the process of creation. It has been suggested that a stable definition of ‘life’ is impossible and that synthetic biologists are confused over what life is, where it begins and particularly, how complex it must be