By 2050, it will take 100 billion land animals to provide the world's population with meat, dairy, eggs and leather goods. Maintaining this herd will take a huge, potentially unsustainable toll on the planet.
Synthetic biology opens up exciting new opportunities for research and industry. Although the work of synthetic biologists presents many beneficial applications, it also raises potentially serious ethical concerns. Therefore, clear ideas must be formed regarding its ethical and social implications, e.g., public perception, safety, security, intellectual property rights and so on. In this review, the authors identified four issues relevant to synthetic biology and discussed associated ethical and practical implications. By weighing these perspectives of all sides, this paper clarifies the point that synthetic biology, as an emerging discipline with many anticipated benefits and positive impacts on society, can acquire moral support and ethical defence. Therefore, synthetic biologists should not be shackled with heavy ethical chains, but we must ensure that research is conducted under strict control and effective supervisory methods.
A team of researchers from the University of Gent are developing Dewpal, a 3D printed water collector that integrates synthetic biology, to help combat water scarcity. They are currently raising funds to bring their project to the International Genetically Engineered Machine competition.
The expression of synthetic circuits in host organisms, or chassis, is a key aspect of synthetic biology. Design adjustments made for maximal production may negatively affect the central metabolism and biosynthetic activities of the chassis host. Here, we review recent attempts to modulate synthetic circuit design for optimal production and present models that precisely capture the trade-off between circuit production and chassis growth. We also present emerging concepts for full orthogonalization of synthetic productivity and its decoupling from the endogenous biosynthetic activities of the cell, opening new routes towards robust synthetic circuit expression.
The robot moves slowly along its track, pausing regularly to reach out an arm that carefully scoops up a component. The arm connects the component to an elaborate construction on the robot's back. Then the robot moves forward and repeats the process — systematically stringing the parts together according to a precise design.
Recent progress in the chemical construction of colloidal objects comprising integrated biomimetic functions is paving the way towards rudimentary forms of artificial cell-like entities (protocells). Although several new types of protocells are currently available, the design of synthetic protocell communities and investigation of their collective behaviour has received little attention. Here we demonstrate an artificial form of predatory behaviour in a community of protease-containing coacervate microdroplets and protein–polymer microcapsules (proteinosomes) that interact via electrostatic binding. The coacervate microdroplets act as killer protocells for the obliteration of the target proteinosome population by protease-induced lysis of the protein–polymer membrane. As a consequence, the proteinosome payload (dextran, single-stranded DNA, platinum nanoparticles) is trafficked into the attached coacervate microdroplets, which are then released as functionally modified killer protocells capable of rekilling. Our results highlight opportunities for the development of interacting artificial protocell communities, and provide a strategy for inducing collective behaviour in soft matter microcompartmentalized systems and synthetic protocell consortia.
Should we bring back the wooly mammoth? Or edit a human embryo? Or wipe out an entire species that we consider harmful? The genome-editing technology CRISPR has made extraordinary questions like these legitimate -- but how does it work? Scientist and community lab advocate Ellen Jorgensen is on a mission to explain the myths and realities of CRISPR, hype-free, to the non-scientists among us.
Microbial morphology engineering has recently become interesting for biotechnology. Genes ftsZ and mreB encoding proteins of bacterial fission ring and skeletons, respectively, are essential for cell growth, they both are the most important genes keeping the bacterial shapes including the cell length and width, respectively. Clustered regularly interspaced short palindromic repeats interference, abbreviated as CRISPRi, was for the first time used in this study to regulate expression intensities of ftsZ or/and mreB in E. coli. Five sgRNAs associated with CRISPRi were designed and synthesized, respectively, to target five various locations on genes ftsZ or mreB encoded in the E. coli chromosome, resulting in various reduced expression levels of ftsZ or/and mreB, respectively, forming elongated or/and fatter cells. Repressions on gene expressions of ftsZ or/and mreB could be further intensified by combining various sgRNAs together. It was found that the stronger the repression on genes ftsZ or/and mreB, the longer the E. coli fibers, and the larger the E. coli cells. Combined repressions on expressions of ftsZ and mreB generated long and larger E. coli with diverse morphologies including various sizes of gourds, bars, coccus, spindles, multi-angles and ellipsoids. In all cases, accumulations of intracellular biopolyester polyhydroxybutyrate (PHB) were in direct proportional to the intracellular volumes, ranging from 40-80% PHB in bacterial cell dry weights, depending on the cell volumes increases by the above CRISPRi applications.
Hacking DNA with Rapid DNA Prototyping: Synthetic Biology for Everyone Justin Pahara (Author), Connor Dickie (Author), Ellen Jorgensen (Author) Publication Date
Droplet microfluidics is an active multidisciplinary area of research that evolved out of the larger field of microfluidics. It enables the user to handle, process and manipulate micrometer-sized emulsion droplets on a micro- fabricated platform. The capability to carry out a large number of individual experiments per unit time makes the droplet microfluidic technology an ideal high-throughput platform for analysis of biological and biochemical samples. The objective of this thesis was to use such a technology for designing systems with novel implications in the newly emerging field of synthetic biology. Chapter 4, the first results chapter, introduces a novel method of droplet coalescence using a flow-focusing capillary device. In Chapter 5, the development of a microfluidic platform for the fabrication of a cell-free micro-environment for site-specific gene manipulation and protein expression is described. Furthermore, a novel fluorescent reporter system which functions both in vivo and in vitro is introduced in this chapter. Chapter 6 covers the microfluidic fabrication of polymeric vesicles from poly(2-methyloxazoline-b-dimethylsiloxane-b-2-methyloxazoline) tri-block copolymer. The polymersome made from this polymer was used in the next Chapter for the study of a chimeric membrane protein called mRFP1-EstA∗. In Chapter 7, the application of microfluidics for the fabrication of synthetic biological membranes to recreate artificial cell- like chassis structures for reconstitution of a membrane-anchored protein is described.
Life has always played by its own set of molecular rules. From the biochemistry behind the first cells, evolution has constructed wonders like hard bone, rough bark and plant enzymes that harvest light to make food.
But our tools for manipulating life - to treat disease, repair damaged tissue and replace lost limbs - come from the nonliving realm: metals, plastics and the like. Though these save and preserve lives, our synthetic treatments are rooted in a chemical language ill-suited to our organic elegance. Implanted electrodes scar, wires overheat and our bodies struggle against ill-fitting pumps, pipes or valves.
A solution lies in bridging this gap where artificial meets biological - harnessing biological rules to exchange information between the biochemistry of our bodies and the chemistry of our devices. In a paper published in Scientific Reports, engineers at the University of Washington unveiled peptides - small proteins which carry out countless essential tasks in our cells - that can provide just such a link.
The team, led by UW professor Mehmet Sarikaya in the Departments of Materials Science and Engineering, shows how a genetically engineered peptide can assemble into nanowires atop 2-D, solid surfaces that are just a single layer of atoms thick. These nanowire assemblages are critical because the peptides relay information across the bio/nano interface through molecular recognition - the same principles that underlie biochemical interactions such as an antibody binding to its specific antigen or protein binding to DNA.
Since this communication is two-way, with peptides understanding the "language" of technology and vice versa, their approach essentially enables a coherent bioelectronic interface.
"Bridging this divide would be the key to building the genetically engineered biomolecular solid-state devices of the future," said Sarikaya, who is also a professor of chemical engineering and oral health sciences.
His team in the UW Genetically Engineered Materials Science and Engineering Center studies how to coopt the chemistry of life to synthesize materials with technologically significant physical, electronic and photonic properties. To Sarikaya, the biochemical "language" of life is a logical emulation.
"Nature must constantly make materials to do many of the same tasks we seek," he said.
The UW team wants to find genetically engineered peptides with specific chemical and structural properties. They sought out a peptide that could interact with materials such as gold, titanium and even a mineral in bone and teeth. These could all form the basis of future biomedical and electro-optical devices.
Their ideal peptide should also change the physical properties of synthetic materials and respond to that change. That way, it would transmit "information" from the synthetic material to other biomolecules - bridging the chemical divide between biology and technology.
In exploring the properties of 80 genetically selected peptides - which are not found in nature but have the same chemical components of all proteins - they discovered that one, GrBP5, showed promising interactions with the semimetal graphene. They then tested GrBP5's interactions with several 2-D nanomaterials which, Sarikaya said, "could serve as the metals or semiconductors of the future."
"We needed to know the specific molecular interactions between this peptide and these inorganic solid surfaces," he added.
Their experiments revealed that GrBP5 spontaneously organized into ordered nanowire patterns on graphene. With a few mutations, GrBP5 also altered the electrical conductivity of a graphene-based device, the first step toward transmitting electrical information from graphene to cells via peptides.
In parallel, Sarikaya's team modified GrBP5 to produce similar results on a semiconductor material - molybdenum disulfide - by converting a chemical signal to an optical signal. They also computationally predicted how different arrangements of GrBP5 nanowires would affect the electrical conduction or optical signal of each material, showing additional potential within GrBP5's physical properties.
"In a way, we're at the flood gates," said Sarikaya. "Now we need to explore the basic properties of this bridge and how we can modify it to permit the flow of 'information' from electronic and photonic devices to biological systems."
The photosynthetic, autotrophic lifestyle of plants and algae position them as ideal platform organisms for sustainable production of biomolecules. However, their use in industrial biotechnology is limited in comparison to heterotrophic organisms, such as bacteria and yeast. This usage gap is in part due to the challenges in generating genetically modified plants and algae and in part due to the difficulty in the development of synthetic biology tools for manipulating gene expression in these systems. Plant and algal metabolism, pre-installed with multiple biosynthetic modules for precursor compounds, bypasses the requirement to install these pathways in conventional production organisms, and creates new opportunities for the industrial production of complex molecules. This review provides a broad overview of the successes, challenges and future prospects for genetic engineering in plants and algae for enhanced or de novo production of biomolecules. The toolbox of technologies and strategies that have been used to engineer metabolism are discussed, and the potential use of engineered plants for industrial manufacturing of large quantities of high-value compounds is explored. This review also discusses the routes that have been taken to modify the profiles of primary metabolites for increasing the nutritional quality of foods as well as the production of specialized metabolites, cosmetics, pharmaceuticals and industrial chemicals. As the universe of high-value biosynthetic pathways continues to expand, and the tools to engineer these pathways continue to develop, it is likely plants and algae will become increasingly valuable for the biomanufacturing of high-value compounds.
CRISPR has opened up limitless avenues for genetic modification. From disease prevention to invasive species control, Jennifer Kahn discusses the discover, application, and implications of gene drives.
Only 25% of bacterial membrane transporters have functional annotation owing to the difficulty of experimental study and of accurate prediction of their function. Here we report a sequence-independent method for high-throughput mining of novel transporters. The method is based on ligand-responsive biosensor systems that enable selective growth of cells only if they encode a ligand-specific importer. We developed such a synthetic selection system for thiamine pyrophosphate and mined soil and gut metagenomes for thiamine-uptake functions. We identified several members of a novel class of thiamine transporters, PnuT, which is widely distributed across multiple bacterial phyla. We demonstrate that with modular replacement of the biosensor, we could expand our method to xanthine and identify xanthine permeases from gut and soil metagenomes. Our results demonstrate how synthetic-biology approaches can effectively be deployed to functionally mine metagenomes and elucidate sequence-function relationships of small-molecule transport systems in bacteria.
Cancer immunotherapy has captured the medical world’s attention, knocking out a few types of cancer in a small portion of the most desperate patients. But it has bumped into many limitations.
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