SynBioFromLeukipposInstitute

From an evolutionary perspective, yeast has no business producing a pain killer. But by re-engineering the microbe's genome, Christina Smolke at Stanford University in California has made it do precisely that. Smolke and her team turned yeast into a biofactory that, by starting with sugar as a raw ingredient, makes the potent pain-relief drug hydrocodone1.

This feat is a prime example of synthetic biology, in which scientists reprogram cells to replicate products found in nature — or even make more-specialized materials that would never normally be produced by a natural organism.

Synthetic biologists are ambitious. “We'd all love to imagine a world where we could adapt biology to manufacture any product renewably, quickly and on demand,” says Michael Jewett, a synthetic biologist at Northwestern University in Evanston, Illinois. Groups around the world are engineering yeast, bacteria and other cells to make plastics, biofuels, medicines and even textiles, with the goal of creating living factories that are cheaper, simpler and more sustainable than their industrial counterparts. For instance, the biomaterials company Spiber Inc. in Tsuruoka, Japan, has reprogrammed bacteria to churn out spider silk for use in strong, lightweight winter clothing.

But synthetic biologists are going beyond simply producing materials — they are creating complex systems by 'wiring up' genetic parts into circuits. This approach has already resulted in various living switches and sophisticated sensors. For example, Martin Fussenegger's group at the Swiss Federal Institute of Technology (ETH) in Zurich has built biomedical sensors that can detect disease-relevant metabolites in the blood and trigger the production of therapeutic compounds. In mice, these biosensors successfully staved off gout and obesity, and treated the skin disease psoriasis2 (see 'Living pills').

Frankenflies Sent To Defeat Monster Mosi: Zika in the English press

Chromatin regulators play a major role in establishing and maintaining gene expression states. Yet how they control gene expression in single cells, quantitatively and over time, remains unclear. We used time-lapse microscopy to analyze the dynamic effects of four silencers associated with diverse modifications: DNA methylation, histone deacetylation, and histone methylation. For all regulators, silencing and reactivation occurred in all-or-none events, enabling the regulators to modulate the fraction of cells silenced rather than the amount of gene expression. These dynamics could be described by a three-state model involving stochastic transitions between active, reversibly silent, and irreversibly silent states. Through their individual transition rates, these regulators operate over different time scales and generate distinct types of epigenetic memory. Our results provide a framework for understanding and engineering mammalian chromatin regulation and epigenetic memory.

One of the top science stories of 2012 involved a furore about the wisdom of enhancing the transmissibility of the H5N1 avian influenza virus in ferrets. In that same year, fears mounted that do-it-yourself (DIY) biologists would cook up their own versions of the virus using information published in the academic press.

Now, journalists and others are again targeting the citizen-science community — a group of people with or without formal training who pursue research either as a hobby or to foster societal learning and open science — amid fears about the nascent gene-editing technology CRISPR–Cas9. In January, the San Jose Mercury News ran an article under a pearl-clutching headline: “Bay Area biologist's gene-editing kit lets do-it-yourselfers play God at the kitchen table.” And although they are much less alarmist, scholars are advising policymakers to consider the potential uses of gene editing “outside the traditional laboratory setting” (R. A. Charo & H. T. Greely Am. J. Bioeth. 15, 11–17; 2015).

Welcome to the CRISPR zoo
Birds and bees are just the beginning for a burgeoning technology.

Just under a year ago, a molecular-biology technique was thrust onto the world stage. Researchers in China announced that they had used the nascent gene-editing tool CRISPR–Cas9 to modify the genomes of human embryos, triggering a major ethics debate.

Yet while this controversy has been playing out, researchers the world over have rushed to use the tool to tinker with the genomes of human somatic cells, viruses, bacteria, animals and plants, and it's in these contexts that the technique promises to have more immediate impact. This issue of Nature examines what's going on at the CRISPR frontiers.

Expanding the Synbio Toolbox: Microbial Communities Engineering by Konstantinos Vavitsas

Science seeks to understand the mechanisms of nature, to develop tools of investigation and to make useful and sometimes revolutionary things with which to build our future. And every now and again, a piece of science comes along that seems like a work of art.

All of this was exemplified by a research paper published in Nature ten years ago that, literally, produced smiles (see Nature 440, 297–302; 2006). Using an astoundingly simple and general method to assemble strands of DNA into arbitrary shapes, the research generated ‘smileys’ that graced the cover of Nature and announced the arrival of DNA origami to the world.

The robustness of this method changed the game for DNA nanotechnology, which has since developed at an astonishing pace. It is a beautiful demonstration of how science can progress.

Related stories
Bioengineering: What to make with DNA origami
Folding DNA to create nanoscale shapes and patterns
The concept behind DNA origami was laid down in the early 1980s by crystallographer Nadrian Seeman, who realized that the ability of DNA molecules to carry and transfer information according to strict base-pairing rules could be used to rationally assemble structures with precisely controlled nanoscale features.

This unprecedented level of programmability makes DNA a unique building material. Nanodesigners have embraced the biomolecule to fabricate intricate tiled patterns, boxes with lids that can be opened and arrays of precisely located binding elements that can incorporate proteins, dyes and other functional materials into regular lattices.

Pivotal to the success of DNA as a nanoscale building material have been automated methods to synthesize short DNA molecules of any sequence. A detailed understanding of how base-pairing translates into the formation of DNA double helices has also been crucial. Such helices control the shapes into which DNA molecules with given sequences will fold.

DNA origami provides the missing ingredient: a versatile yet straightforward assembly method. Computer-aided design programs determine how DNA scaffolds can be folded to realize desired structures, as well as which short DNA strands, or staples, are needed to hold the structures in shape.

Individual structures can also be assembled into more complex patterns, and sites that bind to functional materials can be introduced at any position.

The many eye-catching structures that have been built have pleased those of us with an appreciation of beauty. But even the most creative science will ultimately face the question: what is the point?

DNA nanotechnology has long searched for relevance. It is unrivalled in its ability to build complex structures with near-atomic precision, but the results tend to be labile, soft and so small that it is a challenge to put them to practical use.

Yet applications that address basic problems in science have emerged. DNA structures can serve as tools for determining the structures of proteins or as templates for assembling electronic components and basic devices. Responsive DNA structures can target diseased cells, and artificial membrane channels formed from DNA can act as single-molecule sensors.

Real-world applications might become feasible through recent developments — for example, improvements to the folding process that reduce assembly time and boost yield. Initial steps have also been taken to efficiently pair DNA nanostructures with technologically relevant substrates.

Many challenges remain, and DNA nanotechnology is far from maturity. But a growing number of scientists are entering the field to make more than just art. Watch this space.

What if we could program living cells to do what we would like them to do in the body? Having such control—a major goal of synthetic biology—could allow for the development of cell-based therapies that might one day replace traditional drugs for diseases such as cancer. In order to reach this long-term goal, however, scientists must first learn to program many of the key things that cells do, such as communicate with one another, change their fate to become a particular cell type, and remember the chemical signals they have encountered.

Now a team of researchers led by Caltech biologists Michael Elowitz, Lacramioara Bintu, and John Yong (PhD ’15) have taken an important step toward being able to program that kind of cellular memory using tools that cells have evolved naturally. By combining synthetic biology approaches with time-lapse movies that track the behaviors of individual cells, they determined how four members of a class of proteins known as chromatin regulators establish and control a cell’s ability to maintain a particular state of gene expression—to remember it—even once the signal that established that state is gone.

The researchers reported their findings in the February 12 issue of the journal Science.

Expression of the genome is controlled by an intricate “web” of proteins, chemical modifications, and RNA that together organize genomic DNA into chromatin. Molecular studies of the various forms and levels of chromatin organization are advancing rapidly, revealing an increasing number of connections between chromatin and cellular and disease processes, as well as a fast-expanding web of known chromatin factors (1). On page 720, Bintu et al. take a radically different approach to dissecting chromatin, focusing not on molecular but on “algorithmic” chromatin biology (2). By studying how individual chromatin regulators (CRs) operate to produce distinct gene expression outputs within individual cells, they find that chromatin's complexity can be reduced into an elegant and unifying model of gene regulation.

Supercomputers have the power to carry out unimaginably complex computations, but there is one major problem – they use a ton of energy. According to a report from Business Standard, however, scientists have made a stunning new development that could solve the energy problem for supercomputers once and for all.

Researchers have made a model biological supercomputer, which could process information quickly and accurately using parallel networks like a traditional supercomputer would. It runs on biological processes similar to the ones that power all living cells.

According to Dan Nicolau from McGill University in Montreal, “We’ve managed to create a very complex network in a very small area.” The scientists took a number of cues from the way nature transfers energy, using Adenosine triphosphate, or ATP, as the main source powering the new biological supercomputer.

Researchers combined geometrical modeling and the latest in computer engineering to create a largely capable machine on a seriously tiny scale. The computer hasn’t replaced some of the world’s top supercomputers just yet, but the demonstration that it actually works is a huge step forward.

The main chip in the biological supercomputer resembles a birds eye view of a busy city, and measures only 1.5 cm across. The major development was switching out traditional microchips that move electrons with a charge for a new chip that uses short protein strings called biological agents which travel around in the circuit, propelled by ATP.

The benefit of using biological agents is that there is little heat generated as the computer runs. The new chips allow supercomputers to operate using significantly less energy than before. We may be leaving the days where a supercomputer needs its own power plant to function behind.

The super computer was proficient at solving a complex classical mathematical problem using parallel computing in the same way a normal supercomputer would, but researchers say they still have a long way to go before it can take on Watson and the like.

A press release from McGill University describing the details of the study can be found here.

Policy: Reboot the debate on genetic engineering

Whenever a paper about CRISPR–Cas9 hits the press, the staff at Addgene quickly find out. The non-profit company is where study authors often deposit molecular tools that they used in their work, and where other scientists immediately turn to get them. It is also where other scientists immediately turn to get their hands on these reagents. “We get calls within minutes of a hot paper publishing,” says Joanne Kamens, executive director of the company in Cambridge, Massachusetts.

Accusations of errors and deception fly in CRISPR patent fight