SynBioFromLeukipposInstitute

by
JEFFREY MARLOW

"For millennia, people have gone out of their way to change the biological world around them. We’ve killed threatening species, domesticated others, and manipulated the habitats of still others to make food production and basic survival an easier undertaking. So the notion that our tinkering with nature is a fundamental departure from a past Eden in which we were “a part of nature” is a false dichotomy: every action we take – and some have been more intentional than others – contributes to a changing world.

 The potential magnitude of our intervention, however, is greater today than ever before. Before the advent of molecular biology, the complexity of living systems kept the underlying mechanisms of our tinkering obscure. We may engage in selective breeding (a crude form of biological engineering) to produce a more productive crop or a cuter dog, but our metric of selection – size of an ear of corn, or furriness – is the end result of millions of intricate biological interactions. Following the great reductionist tradition of experimental science, we’ve traced biological function to the genetic level and are now looking for codified ways of enacting discrete interventions in predictable ways. This is synthetic biology: a young field promising great things.  Kevin Munnelly is the President and CEO of Gen9, a company founded by some of the biggest names in synthetic biology research to commercialize a better way of synthesizing DNA. In a recent article published in the journal ACS Synthetic Biology, Munnelly outlines the transformative potential of the field and identifies a key obstacle standing in its way: standardization. As experimental techniques have advanced, individual researchers have jumped right in, designing new genes or regulatory elements, seeing how they affect a microbe, and publishing the results. Another scientist may have accomplished the same feat in a different way, leading future investigators unclear on which method is most desirable. If there were a trusted repository of DNA sequences vetted to produce certain results to spec, it would save a lot of time and minimize the number of variables in a given experiment. Standardization of parts is not a particularly glamorous field of work, but, leading synthetic biologists, agree, it’s essential. Imagine trying to construct a Boeing Dreamliner from a heap of metal and wires. Standard parts get everyone on the same 8.5”x11” page. Fortunately, the global community of synthetic biology coppersmiths is already building a stockroom. The Registry for Standard Biology Parts is up to more than 7000 components. “These are all annotated and confirmed gene sequences,” explains Munnelly, “vetted through peer review publications or public companies that provide validation.” Things like gene promoters, protein coding domains, termination sequences, plasmids, vector sequences, or genes for specific functions...."

http://bit.ly/18Dfpgl

By Christina Agapakis 

"What is the origin of life on Earth? What is the future of life in the age of synthetic biology? These are two of the biggest questions of contemporary biology, and the questions that drive Adam Rutherford’s new book, Creation: How Science is Reinventing Life Itself, a compelling and accessible two-part look through the history and future of living cells. Through chapters that span the early history of microscopy to recent debates on the regulation of biotechnology and genomics, Rutherford tells the complicated story of the science of life as it might have been and as it might be. These two difficult questions, of origins and offspring, have been tightly linked in the life sciences for over a century. In the work of engineer-biologists like Jacques Loeb–who at the beginning of the 20th century sought to create “artificial life” through manipulation of sea urchin eggs–engineering was a tool for experimentation to better understand biology. For Loeb, engineering could be used to examine the validity of biological theory: “the proof of the explicability of any single life phenomenon is furnished as soon at it is successfully controlled unequivocally through physical or chemical means or is repeated in all details with nonliving materials.” Echoes of this sentiment are found everywhere in synthetic biology today, where Richard Feynman’s much more quotable remark is frequently invoked: “What I cannot create, I do not understand.”..."

http://bit.ly/12GWKhP

DIYBio Hangout: Wed 12th June 11am PDT http://bit.ly/12DXswc

By Christina Agapakis 

*Bacteria are single celled organisms that can do amazing things in multicellular groups, with complex coordinated behaviors emerging from the interaction of genetic networks, chemical environments, and the physics of cell growth. Last year I wrote about the work of Tim Rudge and Fernan Federici and their incredible images of bacterial growth patterns. Their paper, with colleagues from the Haseloff Lab at the University of Cambridge, was recently published in ACS Synthetic Biology, showing how complex fractal patterns in colonies of E. coli emerge simply from the physical interactions of rod shaped cells.
In this experiment, E. coli cells are labelled with two colors of fluorescent protein (they are otherwise genetically identical) and seeded at low density onto a surface. As they grow and divide, the rod shaped cells begin to bump into each other, creating jagged boundaries between the two fluorescent populations. These jagged lines are fractal, self-similar at many scales. Using their CellModeller program, the team found that they could accurately model this fractal behavior by including only physical parameters like viscous drag, cell shape, and growth rate, rather than biological properties like cell-cell communication or chemotaxis. Indeed, when they used E. coli mutants that were spherical instead of rod-shaped, the fractal pattern disappeared..."

http://bit.ly/ZFKtWN

Printing innovations provide tenfold improvement in organic electronics http://bit.ly/12d2PRx

by
Daniel E. Agnew, Brian F. Pfleger

"Constructing polycistronic operons is an advantageous strategy for coordinating the expression of ­multiple genes in a prokaryotic host. Unfortunately, a basic construct consisting of an inducible promoter and genes cloned in series does not generally lead to optimal results. Here, a combinatorial approach for tuning relative gene expression in operons is presented. The method constructs libraries of post-­transcriptional regulatory elements that can be cloned into the noncoding sequence between genes. Libraries can be screened to identify sequences that optimize expression of metabolic pathways, multisubunit proteins, or other situations where precise stoichiometric ratios of proteins are desired."

http://bit.ly/ZZjKXx

 

byTarl W. Prow, Daniel Sundh, Gerard A. Lutty "Noninvasive detection of biological responses to reactive oxygen species (ROS) in vivo could shed light on mechanisms at work in diverse areas like developmental dynamics, therapeutic effectiveness, drug discovery, pathogenic processes, and disease prevention. Research on ROS is usually dependent on in vitro models without translational relevance. Nanoscale (<100 nm) particulates are attractive carriers and platforms for biosensor technology due to their small size, flexible assembly, and favorable toxicity profiles. Intracellular signalling pathways activated in response to ROS have been well documented and mechanisms elaborated. Likewise, there is a wealth of genetic reporter systems that utilize fluorescent proteins capable of being monitored noninvasively. We combined these elements into a platform technology that utilizes nanoparticle-tethered synthetic genetic elements that respond to cellular response elements to report endogenous responses to oxidative insult through fluorescent gene expression. We envision the future of this technology to play a research role quantifying oxidative stress in vivo and a future clinical role as an automated theragnostic for ROS-related diseases. The production of this nanobiosensor technology utilizes off-the-shelf components and can be carried out in a molecular biology laboratory. Assessment of fluorescent protein expression can be done with noninvasive imaging and quantitative protein expression analysis. This is a flexible nanoparticle-based reporter system for monitoring in vivo responses to ROS...."http://bit.ly/15U7uqE

by
Erika Check Hayden

"It is a paradox that bedevils genomic medicine: despite near-universal agreement that doctors and geneticists should exchange more data, there has been scant movement towards achieving this goal.

 Now, a consortium of 69 institutions in 13 countries hopes to address the problem by creating an organization to enable the free flow of information in genomic medicine. On 5 June, the consortium, which is calling itself the ‘global alliance’, announced that the organization will develop standards and policies to encourage data-sharing of a person’s DNA sequence combined with clinical information. The alliance’s founders are basing their model on the World Wide Web Consortium, which in the 1990s established standards for the programming language HTML and spurred the growth of web pages across the Internet....."

http://bit.ly/11pw3aV

Figure: Children making DNA ladders out of plasticine as part of a Science, Art and Writing (SAW) project on the theme of synthetic biology.

*Building foundations for an open perspective on synthetic biology research and innovation* 

by
Jenni Rant, Joyce Tait

"Most present day scientists are extremely specialized in their respective fields and hard-wired into a peer review system that forms an integral part of research. Regulations to limit negative impacts of their research together with guidelines to ensure that research is carried out ethically are pervasive. Scientists collaborate on projects that bring complementary expertise together and are well equipped to share factual, accurate and relevant accounts of their research within the scientific community. The global communication network, increasingly driven by social media, enables the latest findings in research to be shared at an almost synaptic speed with recipients who perceive this knowledge in diverse ways. One could assume that the translation of research into a language accessible to a broad audience would be easy, contributing to maintaining informed public assessment of research and innovation, and also encouraging a more general interest in science as part of society. However, the reality has been patchy communication that is often reactive, triggered by recent developments and potential negative publicity rather than carefully considered proactive engagement. The recent measles outbreak serves as a powerful example of how messages from a single scientific paper published in 1998 caused a ripple effect leading to public concern, reduced uptake of vaccination and a general mistrust of scientists and government organizations. The paper has since been retracted (Wakefield et al., 1998; The Editors of The Lancet, 2010) but the implications demonstrate how society processes, disseminates and reacts to information. When a new area of scientific advancement emerges from basic research, communication in a wide variety of forms will be key to framing that technology in the minds of members of the public, affecting market potential and the regulatory systems derived through the political process. Restrictions imposed by the UK government in 2004 for the cultivation of a herbicide-resistant maize variety were deemed too unfavourable for economic viability even after Farm Scale Evaluation trials showed that it caused less damage to wildlife than conventional varieties (Mason, 2004). In Europe discussions on the future governance of new technologies such as synthetic biology frequently refer to the genetic modification (GM) crop experience, where negative public framing of GM technology, driven by a pressure group campaign with uncritical media support, has proven very resistant to change, despite strong and consistent evidence of the benefits of GM crops and their relative safety compared to the pesticides they replace. The prospect of another polarized public debate of the type that has surrounded GM crops had already convinced policy-makers and scientists to pay early attention to public dialogue on synthetic biology (Bhattachary et al., 2010). Communication processes that are balanced and evidence-based will be increasingly important in the framing of new technologies or the re-framing of existing ones...."

http://bit.ly/12uYyKI

*Building foundations for an open perspective on synthetic biology research and innovation* 

by
Jenni Rant, Joyce Tait

http://bit.ly/16KQZRz

*Glowing plants spark debate* 

by
Ewen Callaway

"Among the many projects attracting crowd-sourced funding on the Kickstarter website this week are a premium Kobe beef jerky, a keyboard instrument called a wheelharp and a small leafy plant that will be made to glow in the dark using synthetic-biology techniques.

 The Glowing Plant project, which ends its fund-raising campaign on 7 June, seeks to engineer the thale cress Arabidopsis thaliana to emit weak, green-blue light by endowing it with genetic circuitry from fireflies. If the non-commercial project succeeds, thousands of supporters will receive seeds to plant the hardy weed wherever they wish. The US government has no problem with this prospect, yet some experts and industry watchers are jittery. They fear that distributing the plants could set a precedent for unsupervised releases of synthetic organisms, and might foster a negative public perception of synthetic biology — an emerging experimental discipline that involves genetically engineering organisms to do useful tasks.
The project, based in the San Francisco Bay Area in California, was conceived as a public demonstration of synthetic biology using gene-writing software and lab-made DNA molecules. The effort also reflects a ‘DIY biology’ movement that seeks to make biotechnology more accessible to the public. “The central goal of the project is to inspire people and educate people about this technology,” says entrepreneur and project co-founder Antony Evans. He and his colleagues — Omri Amirav-Drory, founder of synthetic-biology software firm Genome Compiler in Berkeley, California, and Kyle Taylor, a former biology graduate student at Stanford University in California — set out to make Arabidopsis glow because the feat seemed achievable in a simple garage lab. “There are some people in synthetic-biology circles who would yawn at what we’re doing,” Evans says. Making plants glow has been possible since the 1980s, when scientists added a gene encoding the firefly enzyme luciferase to a tobacco plant. When sprayed with the chemical substrate luciferin, the plant glowed temp­orarily (D. W. Ow et al. Science 234, 856–859; 1986). In 2010, another group engineered a tobacco plant to have its own weak glow, using bacterial genes instead (A. Krichevsky et al. PLoS ONE 5, e15461; 2010). Also in 2010, a team at the University of Cambridge, UK, created a genetic circuit in bacteria that makes both firefly luciferase and luciferin, so that the bacteria glow continuously (go.nature.com/4nxcao). The Glowing Plant team plans to tweak the genes in that circuit so that they work in plants....."

http://bit.ly/ZtRud8

Creating the creators: nanomachine mimics protein synthesis http://bit.ly/11g9t3i

*Craig Venter on Synthetic Life, Genome Sequencing*

Video
"Craig Venter, one of the first scientists to sequence the human genome, spoke to WSJ at the Singularity University conference."

http://on.wsj.com/13V1egq

 http://bit.ly/ZDb5rq

*The exhibition “Yours Synthetically” is all about the thematic topic of synthetic biology* 

by MARTIN HIESLMAIR

"Mr. Gardiner, as we are doing this interview you are collecting artistic works for the next exhibition at the Ars Electronica Center with the English title called “Yours Synthetically” that deals with synthetic biology. Why is this topic so relevant for us nowadays?

 If we look at it purely from the scientific point of view we can say that even from Robert Hooke who used the microscope to discover the cell, the science of biology has continually developed alongside new technologies. The discovery of the double helix and the structure of DNA and all the other milestones of scientific progresses led to the understanding that we could cut and paste genetic information from one organism to another. Early genetic experiments progressed to experiments by modern biologist like Craig Venter, who took a synthetic genome put it into a cell and replaced the old genome that was in the cell, and it started to reproduce. They then examined the new cells and discovered that the synthetic genome had completely replaced the organic one. So to use the computer metaphor – which is quite popular in these studies – we took the hardware of the cell and we changed the software. For a biologist this is very crude. This idea of synthetic biology being an engineering approach to nature – what people find quite frightening – actually is too simplistic. Engineering implies that you know everything that can happen, like you would know that a building will stand even in an earthquake. But how can a synthetic biologist or engineer know what impact of this very long sequence can have on the organism, on the whole environment? The word engineering was kind of being cut out because many people were quite afraid of this – genetic engineering if you remember is what’s called during the past decades. Synthetic biology is partly an attempt by science to reframe this whole field and separate it from the public relations disaster of Genetic Engineering....."

http://bit.ly/15UdZK7

The future scientist will do coding and designing abstraction. Lab work is will be done by robots or outsourced.....

*A growing number of biotechnology companies employ a skeleton crew of managers and outsource hands-on science.*

Biotechnology: Virtual reality
by
Heidi Ledford

"If Rosana Kapeller has her way, her company will develop treatments for scourges such as cancer, cardiovascular disease and diabetes. And it will do so with only 12 full-time employees and no wet labs.

Kapeller shares a quiet office with eight colleagues at the headquarters of Nimbus Discovery in Cambridge, Massachusetts. The rest work from their homes in Missouri, Connecticut, Rhode Island and New York. This skeleton crew manages the company's operations and computer analyses; all hands-on experiments are outsourced to an international assembly of contract-research organizations (CROs). “It's a lot like managing a lab down the hall,” says Kapeller, the company's chief scientific officer. “But instead of down the hall, the lab's in China and we're using Skype.” Such is life at a 'virtual' biotechnology company, a lean, nimble model that is gaining popularity among cash-hungry start-ups. These companies consist of as few as one full-time employee who oversees a drug from preclinical development to tests in patients, all in the hands of outside contractors. To take advantage of this niche, scientists must have the management experience to run a remote team of researchers, and may need the financial backing to launch a company on their own. Aspirants should also be prepared for quick turnover with regard to projects and jobs: virtual start-ups are often designed to sell off individual projects — or the full company — to larger firms...."

http://bit.ly/11mC7zX

*Quantum thermometer inside a living cell?*

by

Steve Koppes

"Published in the Proceedings of the National Academy of Sciences (PNAS), the papers are both based on the manipulation of the same material—an atomic-scale defect in diamond known as the nitrogen vacancy center.

Both works also leverage the intrinsic “spin” of this defect for the applications in temperature measurement and information processing. This spintronics approach involves understanding and manipulating the spin of electronics for technological advancement.“These studies build on research efforts undertaken over the last 20 years to isolate and control single electronic spins in the solid state,” says David Awschalom, a principle investigator on both papers and a molecular engineering professor at the University of Chicago. “Much of the initial motivation for working in this field was driven by the desire to make new computing technologies based on the principles of quantum physics.“In recent years the research focus has broadened as we’ve come to appreciate that these same principles could enable a new generation of nanoscale sensors.” Control qubits with lightIn the first PNAS paper, Awschalom and six co-authors at the University of California, Santa Barbara and the University of Konstanz describe a technique that offers new routes toward the eventual creation of quantum computers, which would possess far more capability than modern classical computers.In this application, Awschalom’s team has developed protocols to fully control the quantum state of the defect with light instead of electronics.The quantum state of interest in this defect is its electronic spin, which acts as quantum bit, or qubit, the basic unit of a quantum computer.In classical computers, bits of information exist in one of only two states: zero or one. In the quantum mechanical realm, objects can exist in multiple states at once, enabling more complex processing.This all-optical scheme for controlling qubits in semiconductors “obviates the need to have microwave circuits or electronic networks,” Awschalom says. “Instead, everything can be done solely with photons, with light.”As a fully optical method, it shows promise as a more scalable approach to qubit control. In addition, this scheme is more versatile than conventional methods and could be used to explore quantum systems in a broad range of materials that might otherwise be difficult to develop as quantum devices.Single spin thermometersResearchers describe the quantum thermometer application in a second PNAS paper. The technology represents a new direction for the manipulation of quantum states, which is more commonly linked to computing, communications, and encryption.In recent years, defect spins had also emerged as promising candidates for nanoscale sensing of magnetic and electric fields at room temperature. With thermometry now added to the list, Awschalom foresees the possibility of developing a multifunctional probe based on quantum physics."

http://bit.ly/10TB3bk

*Grand challenges in synthetic biology to be accomplished*

by
Pengcheng Fu

"When engineering science meets biological science, synthetic biology is created. Over the past half century, systems engineering has seen numerous successful applications in the engineering field such as manufacturing, electronics, telecommunications, computer and networks, etc. At the same time, biological systems have been dealt in a reductionist way which resulted in accumulation of numerous but relatively fragmented biological information on genes and proteins, and their interactions. With the advent of genomics and other high-throughput technologies, biological paradigm has been shifted to a holistic view on a living system as a whole for understanding of complex life phenomena and living systems and for modification of genes, proteins, metabolites and other cellular components in order to obtain novel functions/products. 

 As an emerging biological research field, synthetic biology has shown its potential in application of engineering formalisms to design and build functional modules from nucleic acid and protein “parts” and then to integrate such modules into an existing biological systems for novel functions, or to create novel life forms by reconstructing the cellular signaling, regulatory and metabolic building blocks. The artificially re-designed biological systems may allow for experiments that would be too difficult, if not impossible, to be conducted in their full natural context. Although the ultimate goals are such as the creation of artificial life, so far applications of synthetic biology are typically demonstration of engineering concepts, systematic design and module assembling in cellular systems (Purnick and Weiss, 2009). The resultant biological parts and modules been designed include switches (Gardner et al., 2000; Kramer et al., 2004), logic gates (Hooshangi et al., 2005), pulse generators (Basu et al., 2004), time-delayed circuits (Weber et al., 2007), oscillators (Stricker et al., 2008), sensors (Basu et al., 2005), and regulators (Zhang et al., 2012). These modules can be used to regulate gene expression, manipulate protein function, modify metabolism and signal cell–cell communication. On the other hand, care must be taken that different from engineering systems, biological systems are capable of replication, extremely complex in their nonlinear network and component interactions, and with less known mechanism for both their basic elements and the whole system. As we ponder the future directions in biology research that combines the exploratory nature of biology with the constructive nature of engineering (Purnick and Weiss, 2009), there remain many main scientific challenges in synthetic biology, some of which are as follows: 1. Modeling for synthetic biology practice. Cells can be viewed as interwoven networks of interactions among proteins, DNA, and metabolites involved in signaling, material and energy transfer. Understanding of cellular systems and then modification of them require quantitative models which are capable of predicting complex intracellular interactions of biological elements, their modules and networks. A whole cell computational model has been built up for this purpose that has used data from more than 900 scientific papers to account for every molecular interaction that takes place in the life cycle of Mycoplasma genitalium (Karr et al., 2012). This type of detailed models need to be expanded to allow simulation for synthetic biology applications, such as prediction of complex phenotypes for biological chassis bearing heterologous genetic parts, or compatibility of cellular networks and the incoming artificial modules. 2. Device modularization and standardization. So far many genetic device and small modules have been constructed and accumulated in the first wave of synthetic biology (Purnick and Weiss, 2009). These basic elements have been simple and are used to perform isolated cellular functions. In order to create larger functional architecture by synthetic biology using engineering design principles, modularization and standardization become a necessity. However, the non-linear and uncertain nature of biological systems makes standardization of parts a nontrivial task. More efforts are needed to create general and stable artificial parts and modules which can be “plugged and played” by synthetic biologists in considering the characteristics of cellular systems, such as cell growth and differentiation, mutation, evolution and other cellular activities. 3. Encoding life with non-natural codons. Biosynthesis of proteins with non-natural amino acids has drawn great interests with the prospects for novel, artificial genetic code which may ultimately lead to the creation of new life forms. Production of proteins and/or man-made polymers with non-natural amino and keto acids (Wang et al., 2003) has been achieved by forming an acylated transfer RNA chemically (Noren et al., 1990; Robertson et al., 1989), by use of modified aminoacyl tRNA synthetases (Mehl et al., 2003; Chin et al., 2003), or by producing new codons with four or five bases (Hohsaka et al., 2001a, b), or codons containing non-natural base pairs (Wang and Schultz, 2002). This technology need to be spurred by the goals of using existing cellular machinery to produce proteins with desirable new functions (Mehl et al., 2003) and to design codons and protein scaffolds to develop protein engineering for novel therapeutics (Nuttall and Walsh, 2008). 4. Quest from minimum genome. Synthetic biologists are interested in the quest for artificial cells, using either “top-down” or “bottom-up” approach which aims at determining the smallest set of genes, molecules and structures for cell replication, growth, metabolism, and regulation that comprise life from two different aspects. By the top-down method, a minimal genome is generated by systematically reducing a cell’s genome until it loses its functions (Glass et al., 2006). On the other hand, the bottom-up approach involves assembling the components or information units from scratch until an aspect of life emerges (Bedau 2003). Study for such a minimal gene set and its features may shed light into the basics of cellular functions and help to determine the subset of essential genes in most species. Artificial cells allow combining properties of biological systems for therapeutic and diagnostic applications. It is an attempt to mimic some of the biological processes of a real cell. The challenge is how to explore the origins of life from the biosynthesis of living systems in the laboratory. 5. Non-coding RNA for cellular functions. One of the most important discoveries of the last few years has been the identification of small, non-protein-coding RNAs (ncRNAs) that act as integral regulatory components of cellular networks (Storz, 2002). ncRNAs serve an astonishing variety of functions and thus play important roles in many intracellular processes, from transcriptional regulation, gene silencing, chromosomal replication, through RNA processing and modification, mRNA stability and translation, to protein degradation and translocation, etc. In synthetic biology, ncRNAs have been shown to have advantages in circuit engineering (Callura et al., 2010). Orthogonally acting ncRNA regulators that work independently in the same cell have been used to engineer higher-order regulatory functions (Lucks et al, 2011). Systematic identification and characterization of ncRNAs in genomes has become one of the most exciting challenges in cellular and development biology.  6. Compatibility of genetic elements and cellular chassis. Biological chassis allows heterologous genetic modules to be implanted and tested like what may happen to its engineering counterparts. However, unlike parts used in engineering systems, biological components are usually non-orthogonal, and will interact with genes, proteins and metabolites of the chassis. The adaptation of the implanted modules to the intracellular network “environments” and the compatibility of the biological chassis with the genetic parts assembled remain as the core of current synthetic biology research. ....."

http://bit.ly/10WWc0B