"A method has been developed to produce and integrate single-stranded DNA into genomic locations in bacteria in response to exogenous signals. The system functions similarly to a cellular tape recorder by writing information into DNA and reading it at a later time. Much like other cellular memory platforms, its operation is based on DNA recombinase function. However, the scalability and recording capacity have been improved over previous designs. In addition, memory storage was reversible and could be recorded in response to analogue inputs, such as light exposure. This modular memory writing system is an important addition to the genomic editing toolbox available for synthetic biology."
Competing endogenous RNAs, which include mRNAs, transcribed pseudogenes, long noncoding RNAs (lncRNA), and circular RNA (circRNA), regulate other RNA transcripts by competing for shared microRNA
MicroRNA is a small non-coding RNA molecule containing about 22 nucleotides found in plants, animals, and some viruses, which functions in RNA silencing and post-transcriptional regulation of gene expression
Messenger RNA is a large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression
Pseudogenes are sections of a chromosome that are imperfect, dysfunctional copies of functional genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell
Long noncoding RNA (lncRNA) comprises a large and diverse class of transcribed RNA molecules with a length of more than 200 nucleotides that do not encode proteins, and whose expression is developmentally regulated and that can be tissue- and cell-type specific
Circular RNA (circRNA) is a type of gene regulating noncoding RNA which, unlike the better-known linear RNA, forms a covalently closed continuous loop and that have not been shown to code for proteins
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 base pairs in length, that has many functions but is most notable in the RNA interference (RNAi) pathway where it interferes with the expression of specific genes with complementary nucleotide sequences..."
"DNA PRODUCTION IS becoming cheaper than ever, propelled down a Moore’s law curve by maturing technologies and cheaper reagents. This new biosynthetic industry allows researchers to order up a customized sequence for overnight delivery.
But many users don’t just want a chain of nucleotides, they want ready-to-use sequences that can be inserted into a cell to make a product of interest. Such DNA products, known as constructs, include two components – a vector that will be read by host machinery and initiate transcription, and an inserted gene that will generate the non-native biomolecule. Constructs can be thousands of bases in length, but once they’re uploaded to the cell, production should be good to go.
This niche is where Genscript is staking its claim. “We’re the world’s largest provider for construct based gene synthesis,” says Jeffrey Hung, a Genscript Vice President, “and a lot of our growth is coming from higher demand for biologics,” or medicinal biomolecules generated through a microbial host (as opposed to an exclusively chemical synthetic process). Most frequently, the company takes orders for non-native products to be expressed in a different organism, turning the unwitting target cell into a biofactory for recombinant proteins or antibodies. In many cases, biologics – the result of intentional expression of known biomolecules – are safer than uncharacterized but empirically promising small molecules taken from a cellular milieu. And using the cell as a production platform is an appealing prospect: organisms can tune behavior and metabolism to changing conditions, so small fluctuations in temperature or reactant concentration won’t doom a costly industrial process."
"Characteristics adapted from lizards, ivy and other natural materials could help to engineer everyday objects with remarkable properties.
made it so. Similarly, some scientists have gazed at geckos walking up walls and wondered whether humans could do the same. Now they can. In June 2014, a 100-kilogram man wearing a heavy pack climbed up a vertical sheet of glass using only a pair of hand-held paddles made from an advanced material inspired by geckos.
The synthetic gecko skin on the paddles has plenty of company in the world of materials science. Researchers are increasingly looking towards plants and animals for ideas on how to design coatings and textures that imbue surfaces with special properties. The adhesive that ivy uses to cling to walls, for example, has inspired a material that might help damaged tissues to regenerate. Molecules taken from mussel adhesives could provide a way to target cancer cells. And the veins on nasturtium leaves have led to the development of a synthetic surface that could prevent rain from freezing on aeroplane wings or keep grimy fingerprints off smartphone screens. The trick is to take ideas sparked by nature — some of them long in development, others brand new — and make them practical and durable......"
"Compartmentalisation of cellular processes is fundamental to regulation of metabolism in Eukaryotic organisms and is primarily provided by membrane-bound organelles. These organelles are dynamic structures whose membrane barriers are continually shaped, remodelled and scaffolded by a rich variety of highly sophisticated protein complexes. Towards the goal of bottom-up assembly of compartmentalised protocells in synthetic biology, we believe it will be important to harness and reconstitute the membrane shaping and sculpting characteristics of natural cells. We review different in vitro membrane models and how biophysical investigations of minimal systems combined with appropriate theoretical modelling have been used to gain new insights into the intricate mechanisms of these membrane nanomachines, paying particular attention to proteins involved in membrane fusion, fission and cytoskeletal scaffolding processes. We argue that minimal machineries need to be developed and optimised for employment in artificial protocell systems rather than the complex environs of a living organism. Thus, well-characterised minimal components might be predictably combined into functional, compartmentalised protocellular materials that can be engineered for wide-ranging applications."
"The development of novel technologies in the late 19th and early 20th century lead to the creation of major new industries such as the petrochemical, automotive, aviation, and electronic. These industries have improved the lives of billions of people around the globe1 and propelled civilization forward. During the second half of the 20th century the digital revolution changed the world yet again, with the rise of personal computers and the internet. According to the UK Royal Academy of Engineering, we are on the cusp of another revolution—this one based on synthetic biology1. The applications of synthetic biology are broad, ranging from renewable energy production to agriculture. One exciting application that will have profound implications on human health is medicine. This paper will discuss the advent of synthetic biology and its medical applications."
Pamela Peralta-Yahya, Georgia Institute of Technology
Stanley Qi, Stanford University
"Synthetic biology is a discipline wherein living organisms are genetically programmed to carry out desired functions in a reliable manner. This field takes inspiration from our ever-expanding ability to measure and manipulate biological systems, and the philosophical reflections of Schrodinger and Feynman that physical laws can be used to describe and rationally engineer biology to accomplish useful goals. After all, cells are the world’s most sophisticated chemists, and their ability to learn to adapt to changing environments offer enormous potential to solving modern engineering challenges. Nonetheless, biological systems are noisy, massively interconnected, and non-linear, and have not evolved to be easily engineered. The grand challenge of synthetic biology is to reconcile the desire for a predictable, formalized biological design process with the inherent ‘squishiness’ of biology.
Learn Techniques and Perform Research at the Forefront of Synthetic Biology: The course will focus on how the complexity of biological systems, combined with traditional engineering approaches, results in the emergence of new design principles for synthetic biology. The Course centers around an immersive laboratory experience. Here, students will work in teams to learn the practical and theoretical underpinnings of cutting edge research in the area of Synthetic Biology. Broadly, we will explore how cellular regulation- transcriptional, translational, post-translational and epigenetic- can be used to engineer cells to accomplish well-defined goals. Specific laboratory modules will cover the following areas: cell-free transcription and translation systems, high-throughput cloning techniques, computational biology using ordinary differential equations models, biosensor development for metabolic engineering, and CRISPR for genome editing in mammalian cells to regulate synthetic genes and physical cell properties. Students will first learn essential synthetic biology techniques in a four-day ‘boot-camp’, and then rotate through research projects in select areas.
In addition, students will interact closely with a panel of internationally-recognized speakers who will give students a broad overview of applications for synthetic biology, including renewable chemical production and therapeutics, the current state-of-the-art techniques, and case studies in human practices and socially responsible innovation.
Speakers in 2015 include:
Elisa Franco, University of California, Riverside
Nathan Hillson, Harvard Medical School
Mo Khalil, Boston University
Thomas Knight, Ginkgo BioWorks
Vincent Noireaux, University of Minnesota
Pamela Silver, Harvard Medical School
Danielle Tullman-Erceck, University of California, Berkeley
by Kyung-In Jang,Ha Uk Chung,Sheng Xu,Chi Hwan Lee,Haiwen Luan,Jaewoong Jeong, Huanyu Cheng,Gwang-Tae Kim,Sang Youn Han,Jung Woo Lee,Jeonghyun Kim,Moongee Cho,Fuxing Miao,Yiyuan Yang,Han Na Jung,Matthew Flavin,Howard Liu,Gil Woo Kong,Ki Jun Yu,Sang Il Rheeet al.
"Hard and soft structural composites found in biology provide inspiration for the design of advanced synthetic materials. Many examples of bio-inspired hard materials can be found in the literature; far less attention has been devoted to soft systems. Here we introduce deterministic routes to low-modulus thin film materials with stress/strain responses that can be tailored precisely to match the non-linear properties of biological tissues, with application opportunities that range from soft biomedical devices to constructs for tissue engineering. The approach combines a low-modulus matrix with an open, stretchable network as a structural reinforcement that can yield classes of composites with a wide range of desired mechanical responses, including anisotropic, spatially heterogeneous, hierarchical and self-similar designs. Demonstrative application examples in thin, skin-mounted electrophysiological sensors with mechanics precisely matched to the human epidermis and in soft, hydrogel-based vehicles for triggered drug release suggest their broad potential uses in biomedical devices."
What if you could design a house that would be encapsulated in a seed? Then to build that house you just had to plant the seed and add water. The Bio/Nano/Programmable Matter group at Autodesk Research is working to make this possible.
"OVER THE LAST several decades, DNA – the genetic material of life as we know it – has completed a remarkable scientific cycle. In 1953, it was a mysterious blur on an X-ray diffractogram. By the 1970s, it was possible to determine the sequence of short nucleotide chains. And now, a scientist can produce her own genetic code of choice with the click of a mouse.
What happens after the mouse click, after an order for a chain of DNA is sent, is an impressive series of events that represents one of the most mature, yet dynamic, sectors of the biotech industry. DNA synthesis companies range from scrappy start-ups to Cambridge-area behemoths, each touting a distinct set of tools that carves out a slice of the ever increasing pie.
For many groups, the human genome project – the $3 billion effort funded by the U.S. government – was an important launching point that both advanced DNA sequencing and synthesis technology and prompted important questions worthy of further scientific investigation. “We are a direct beneficiary of all the sequencing information that came out of the Project,” says Kevin Munnelly, CEO of Gen9, “and it’s all going to impact synthetic biology and our ability to write DNA.” Jerry Steele, the Director of Marketing for IDT, recalls that “the thing that really helped us take off was synthesizing the oligos for the human genome project. 10 or 15 years ago, it cost a few dollars per base to make oligos,” he recalls, “and now we’re down to a few cents.”
Several different industries are reaping the benefits, from agriculture to clean-tech to pharmaceuticals. Emily Leproust, CEO of Twist Bioscience, thinks the biochemical arms race between pathogens and pharmaceutical companies is worse than most people realize. With increasing antibiotic resistance and a diminished rate of new antibiotic discovery, “we’re going back to an era of pre-penicillin,” Leproust maintains, “and it will be a shock to people.” With affordable methods to produce alternative genes, regulatory structures, or even entire metabolic pathways now available, the range of possible products has grown exponentially. “Now we can make new candidates and new antibiotics that will enable us to start fighting back.”..."
by Zoltán Kis , Hugo Sant'Ana Pereira , Takayuki Homma , Ryan M. Pedrigi , Rob Krams
"In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes."
"Millions of years of evolution have made the biological world into a supremely effective materials-development laboratory. This Outlook examines the ways in which substances found in the natural world are inspiring imitations that might eventually endow humans with superhuman power..."
Genetically identical cells can have many variable properties. A study of correlations between cells in a lineage explains paradoxical inheritance laws, in which mother and daughter cells seem less similar than cousins. See Letter p.468
"Quorum-sensing networks enable bacteria to sense and respond to chemical signals produced by neighboring bacteria. They are widespread: over 100 morphologically and genetically distinct species of eubacteria are known to use quorum sensing to control gene expression. This diversity suggests the potential to use natural protein variants to engineer parallel, input-specific, cell–cell communication pathways. However, only three distinct signaling pathways, Lux, Las, and Rhl, have been adapted for and broadly used in engineered systems. The paucity of unique quorum-sensing systems and their propensity for crosstalk limits the usefulness of our current quorum-sensing toolkit. This review discusses the need for more signaling pathways, roadblocks to using multiple pathways in parallel, and strategies for expanding the quorum-sensing toolbox for synthetic biology."
"Harness the tools and techniques of Rapid DNA Prototyping to build your own sophisticated genetic circuits. This powerful set of modular parts enables you to determine your own complex projects. The power of synthetic biology has never been so accessible!"
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