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When it comes to biomolecules, RNA doesn’t get a lot of love.
Maybe you haven’t even heard of the silent workhorse. RNA is the cell’s de facto translator: like a game of telephone, RNA takes DNA’s genetic code to a cellular factory called ribosomes. There, the cell makes proteins based on RNA’s message.
But RNA isn’t just a middleman. It controls what proteins are formed. Because proteins wiz around the cell completing all sorts of important processes, you can say that RNA is the gatekeeper: no RNA message, no proteins, no life.
In a new study published in Nature, RNA finally took center stage. By adding bits of genetic material to the E. Coli bacteria, a team of biohackers at the Wyss Institute hijacked the organism’s RNA messengers so that they only spring into action following certain inputs.
The result? A bacterial biocomputer capable of performing 12-input logic operations—AND, OR, and NOT—following specific inputs. Rather than outputting 0s and 1s, these biocircuits produce results based on the presence or absence of proteins and other molecules.
“It’s the greatest number of inputs in a circuit that a cell has been able to process,” says study author Dr. Alexander Green at Arizona State University. “To be able to analyze those signals and make a decision is the big advance here.”
When given a specific set of inputs, the bacteria spit out a protein that made them glow neon green under fluorescent light.
But synthetic biology promises far more than just a party trick—by tinkering with a cell’s RNA repertoire, scientists may one day coax them to photosynthesize, produce expensive drugs on the fly, or diagnose and hunt down rogue tumor cells.
Illustration of an RNA-based ‘ribocomputing’ device that makes logic-based decisions in living cells. The long gate RNA (blue) detects the binding of an input RNA (red). The ribosome (purple/mauve) reads the gate RNA to produce an output protein. Image Credit: Alexander Green / Arizona State University
The software of life
This isn’t the first time that scientists hijacked life’s algorithms to reprogram cells into nanocomputing systems. Previous work has already introduced to the world yeast cells that can make anti-malaria drugs from sugar or mammalian cells that can perform Boolean logic.
Yet circuits with multiple inputs and outputs remain hard to program. The reason is this: synthetic biologists have traditionally focused on snipping, fusing, or otherwise arranging a cell’s DNA to produce the outcomes they want.
But DNA is two steps removed from proteins, and tinkering with life’s code often leads to unexpected consequences. For one, the cell may not even accept and produce the extra bits of DNA code. For another, the added code, when transformed into proteins, may not act accordingly in the crowded and ever-changing environment of the cell.
What’s more, tinkering with one gene is often not enough to program an entirely new circuit. Scientists often need to amp up or shut down the activity of multiple genes, or multiple biological “modules” each made up of tens or hundreds of genes.
It’s like trying to fit new Lego pieces in a specific order into a room full of Lego constructions. Each new piece has the potential to wander off track and click onto something it’s not supposed to touch.
Getting every moving component to work in sync—as you might have guessed—is a giant headache.
The RNA way
With “ribocomputing,” Green and colleagues set off to tackle a main problem in synthetic biology: predictability.
Named after the “R (ribo)” in “RNA,” the method grew out of an idea that first struck Green back in 2012.
“The synthetic biological circuits to date have relied heavily on protein-based regulators that are difficult to scale up,” Green wrote at the time. We only have a limited handful of “designable parts” that work well, and these circuits require significant resources to encode and operate, he explains.
RNA, in comparison, is a lot more predictable. Like its more famous sibling DNA, RNA is composed of units that come in four different flavors: A, G, C, and U. Although RNA is only single-stranded, rather than the double helix for which DNA is known for, it can bind short DNA-like sequences in a very predictable manner: Gs always match up with Cs and As always with Us.
Because of this predictability, it’s possible to design RNA components that bind together perfectly. In other words, it reduces the chance that added RNA bits might go rogue in an unsuspecting cell.
Normally, once RNA is produced it immediately rushes to the ribosome—the cell’s protein-building factory. Think of it as a constantly “on” system.
However, Green and his team found a clever mechanism to slow them down. Dubbed the “toehold switch,” it works like this: the artificial RNA component is first incorporated into a chain of A, G, C, and U folded into a paperclip-like structure.
This blocks the RNA from accessing the ribosome. Because one RNA strand generally maps to one protein, the switch prevents that protein from ever getting made.
In this way, the switch is set to “off” by default—a “NOT” gate, in Boolean logic.
To activate the switch, the cell needs another component: a “trigger RNA,” which binds to the RNA toehold switch. This flips it on: the RNA grabs onto the ribosome, and bam—proteins.
String a few RNA switches together, with the activity of each one relying on the one before, and it forms an “AND” gate. Alternatively, if the activity of each switch is independent, that’s an “OR” gate.
“Basically, the toehold switches performed so well that we wanted to find a way to best exploit them for cellular applications,” says Green. They’re “kind of the equivalent of your first transistors,” he adds.
Once the team optimized the designs for different logic gates, they carefully condensed the switches into “gate RNA” molecules. These gate RNAs contain both codes for proteins and the logic operations needed to kickstart the process—a molecular logic circuit, so to speak.
If you’ve ever played around with an Arduino-controlled electrical circuit, you probably know the easiest way to test its function is with a light bulb.
That’s what the team did here, though with a biological bulb: green fluorescent protein, a light-sensing protein not normally present in bacteria that—when turned on—makes the microbugs glow neon green.
In a series of experiments, Green and his team genetically inserted gate RNAs into bacteria. Then, depending on the type of logical function, they added different combinations of trigger RNAs—the inputs.
When the input RNA matched up with its corresponding gate RNA, it flipped on the switch, causing the cell to light up.
Their most complex circuit contained five AND gates, five OR gates, and two NOTs—a 12-input ribocomputer that functioned exactly as designed.
That’s quite the achievement. “Everything is interacting with everything else and there are a million ways those interactions could flip the switch on accident,” says RNA researcher Dr. Julies Lucks at Northwestern University.
The specificity is thanks to RNA, the authors explain. Because RNAs bind to others so predictably, we can now design massive libraries of gate and trigger units to mix-and-match into all types of nano-biocomputers.
Although the technology doesn’t have any immediate applications, the team has high hopes.
For the first time, it’s now possible to massively scale up the process of programming new circuits into living cells. We’ve expanded the library of available biocomponents that can be used to reprogram life’s basic code, the authors say.
What’s more, when freeze-dried onto a piece of tissue paper, RNA keeps very well. We could potentially print RNA toehold switches onto paper that respond to viruses or to tumor cells, the authors say, essentially transforming the technology into highly accurate diagnostic platforms.
But Green’s hopes are even wilder for his RNA-based circuits.
“Because we’re using RNA, a universal molecule of life, we know these interactions can also work in other cells, so our method provides a general strategy that could be ported to other organisms,” he says.
Ultimately, the hope is to program neural network-like capabilities into the body’s other cells.
Imagine cells endowed with circuits capable of performing the kinds of computation the brain does, the authors say.
Perhaps one day, synthetic biology will transform our own cells into fully programmable entities, turning us all into biological cyborgs from the inside. How wild would that be?
Image Credit: Wyss Institute at Harvard University Continue reading
Today marks official launch of the second UK Robotics Week; entries now open in Surgical Robot, Autonomous Driving and School Robot Challenges
London, UK, 7th November 2016. – UK Robotics Week 2017 officially launches today, with a range of robotics activities and challenges open to schools, academic institutions and industry sectors. These activities culminate in a national week of celebration being held 24th – 30th June 2017. The second annual UK Robotics Week is set to be even bigger and better, building on the huge success of the inaugural event. Any institutions or organisations planning to hold their own robotics events – either in the run-up to and during the UK Robotics Week – can also apply now to be included in the official Programme of Activities (please visit www.roboticsweek.uk for details of how to register).
The first ever UK Robotics Week proved a huge success, encompassing a host of events up and down the UK, including public lectures, open labs, hackathons, tech weekends, conferences, and a state-of-the-art robotics showcase held on the last day. The UK Robotics Week initiative is jointly spearheaded by founding supporters, the Engineering and Physical Sciences Research Council (EPSRC), The Royal Academy of Engineering, the Institution of Engineering and Technology, the Institution of Mechanical Engineers and the UK-RAS Special Interest Group, and is being coordinated by the EPSRC UK-RAS network.
As part of the official launch, this year’s School Robot Challenge is now open for entries to all schools nationwide. The competition offers schoolchildren the opportunity to design their own virtual robot bug and teach it to move, with the option of printing their bug in 3D. The challenge aims to develop children’s interest and skills in digital technology, design, science, engineering and biology. This year’s competition has been split into two age group categories – 4-12 years and 13-18 years – with top prizes to be awarded in each. School are actively encouraged to register their interest on the website now to access the information packs and software at http://www.roboticsweek.uk/schoolrobotchallenge.htm
The first Surgical Robot Challenge attracted participation from the world’s leading institutions, with top robotics research teams travelling to the UK to demonstrate their outstanding innovations during last year’s competition finals. The 2017 competition is now open for entry, and any international researchers interested in participating in this prestigious challenge can download all the competition information at http://www.roboticsweek.uk/surgicalrobotchallenge.htm
The second Autonomous Driving Challenge is also launched today. This is an international competition to inspire the next generation of designers and engineers, and involves designing your own vehicle and teaching it to drive autonomously. The challenge is open to everyone: children and adults, amateurs and professionals.
Commenting on today’s official launch, Professor Guang-Zhong Yang PhD, FREng, Director and Co-founder of the Hamlyn Centre for Robotic Surgery, at Imperial College London and Chair of the UK-RAS Network, said: “We have been delighted with the response to UK Robotics Week, which looks set to become one of the key highlights in the science and technology calendar. This is a unique opportunity to celebrate the UK’s technology leadership in robotics and autonomous systems, and for individuals and institutions to get involved – hands-on – with robotics development.”
Professor Philip Nelson, Chief Executive of EPSRC, added: “From inspiring the nation’s budding engineers in STEM subjects to engaging people of all ages in a national debate about the contribution robotic technology can make to society and our economy, we’re looking forward to creating even more of a buzz with UK Robotics Week this year, and shining an even bigger spotlight on the fantastic robotics innovation being driven from the UK.”
For full information about all the activities planned for UK Robotics Week, please visit the website: www.roboticsweek.uk and follow UK Robotics Week on Twitter (@ukroboticsweek)
About the EPSRC UK-RAS Network (http://www.uk-ras.org) : The EPSRC UK Robotics and Autonomous Systems Network (UK-RAS Network) is dedicated to robotics innovation across the UK, with a mission to provide academic leadership in Robotics and Autonomous Systems (RAS), expand collaboration with industry, and integrate and coordinate activities at eight Engineering and Physical Sciences Research Council (EPSRC) funded RAS capital facilities and Centres for Doctoral Training (CDTs) across the country.
Mobile: +44 (0)7747 017654
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Fusion for Energy signs multi-million deal with Airbus Safran Launchers, Nuvia Limited and Cegelec CEM to develop robotics equipment for ITER
The contract for a value of nearly 100 million EUR is considered to be the single biggest robotics deal to date in the field of fusion energy. The state of the art equipment will form part of ITER, the world’s largest experimental fusion facility and the first in history to produce 500 MW. The prestigious project brings together seven parties (China, Europe, Japan, India, the Republic of Korea, the Russian Federation and the USA) which represent 50% of the world’s population and 80% of the global GDP.
The collaboration between Fusion for Energy (F4E), the EU organisation managing Europe’s contribution to ITER, with a consortium of companies consisting of Airbus Safran Launchers (France-Germany), Nuvia Limited (UK) and Cegelec CEM (France), companies of the VINCI Group, will run for a period of seven years. The UK Atomic Energy Authority (UK), Instituto Superior Tecnico (Portugal), AVT Europe NV (Belgium) and Millennium (France) will also be part of this deal which will deliver remotely operated systems for the transportation and confinement of components located in the ITER vacuum vessel.
The contract carries also a symbolic importance marking the signature all procurement packages managed by Europe in the field of remote handling. Carlo Damiani, F4E’s Project Manager for ITER Remote Handling Systems, explained that “F4E’s stake in ITER offers an unparalleled opportunity to companies and laboratories to develop expertise and an industrial culture in fusion reactors’ maintenance.”
Cut-away image of the ITER machine showing the casks at the three levels of the ITER machine. ITER IO © (Remote1 web). Photo Credit: f4e.europa.euIllustration of lorry next to an ITER cask. F4E © (Remote 2 web). Photo Credit: f4e.europa.euAerial view of the ITER construction site, October 2016. F4E © (ITER site aerial Oct). Photo Credit: f4e.europa.eu
Why ITER requires Remote Handling?
Remote handling refers to the high-tech systems that will help us maintain and repair the ITER machine. The space where the bulky equipment will operate is limited and the exposure of some of the components to radioactivity, prohibit any manual intervention inside the vacuum vessel.
What will be delivered through this contract?
The transfer of components from the ITER vacuum vessel to the Hot Cell building, where they will be deposited for maintenance, will need to be carried out with the help of massive double-door containers known as casks. According to current estimates, 15 of these casks will need to be manufactured and in their largest configuration they will measure 8.5 m x 3.7 m x 2.6 m approaching 100 tonnes when transporting the heaviest components. These enormous “boxes”, resembling to a conventional lorry container, will be remotely operated as they move between the different levels and buildings of the machine. Apart from the transportation and confinement of components, the ITER Cask and Plug Remote Handling System will also ensure the installation of the remote handling equipment entering into the vacuum vessel to pick up the components to be removed. The technologies underpinning this system will encompass a variety of high-tech skills and comply with nuclear safety requirements. A proven manufacturing experience in similar fields and the development of bespoke systems to perform mechanical transfers will be essential.
MEMO: Fusion for Energy signs multi-million deal with Airbus Safran Launchers, Nuvia Limited and Cegelec CEM to develop robotics equipment for ITER
To see how the ITER Remote Handling System will operate click on clip 1 and clip 2
To see the progress of the ITER construction site click here
To take a virtual tour on the ITER construction site click here
Cut-away image of the ITER machine showing the casks at the three levels of the ITER machine. ITER IO © (Remote1 web)
Illustration of lorry next to an ITER cask. F4E © (Remote 2 web)
Aerial view of the ITER construction site, October 2016. F4E © (ITER site aerial Oct)
The consortium of companies
The consortium combines the space expertise of Airbus Safran Launchers, adapted to this extreme environment to ensure safe conditions for the ITER teams; with Nuvia comes a wealth of nuclear experience dating back to the beginnings of the UK Nuclear industry. Nuvia has delivered solutions to some of the world’s most complex nuclear challenges; and with Cegelec CEM as a specialist in mechanical projects for French nuclear sector, which contributes over 30 years in the nuclear arena, including turnkey projects for large scientific installations, as well as the realisation of complex mechanical systems.
Fusion for Energy
Fusion for Energy (F4E) is the European Union’s organisation for Europe’s contribution to ITER.
One of the main tasks of F4E is to work together with European industry, SMEs and research organisations to develop and provide a wide range of high technology components together with engineering, maintenance and support services for the ITER project.
F4E supports fusion R&D initiatives through the Broader Approach Agreement signed with Japan and prepares for the construction of demonstration fusion reactors (DEMO).
F4E was created by a decision of the Council of the European Union as an independent legal entity and was established in April 2007 for a period of 35 years.
Its offices are in Barcelona, Spain.
ITER is a first-of-a-kind global collaboration. It will be the world’s largest experimental fusion facility and is designed to demonstrate the scientific and technological feasibility of fusion power. It is expected to produce a significant amount of fusion power (500 MW) for about seven minutes. Fusion is the process which powers the sun and the stars. When light atomic nuclei fuse together form heavier ones, a large amount of energy is released. Fusion research is aimed at developing a safe, limitless and environmentally responsible energy source.
Europe will contribute almost half of the costs of its construction, while the other six parties to this joint international venture (China, Japan, India, the Republic of Korea, the Russian Federation and the USA), will contribute equally to the rest.
The site of the ITER project is in Cadarache, in the South of France.
For Fusion for Energy media enquiries contact:
Tel: + 34 93 3201833 + 34 649 179 42
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