Introducing DOULIX: A Bio-Engineering Platform from Explora Biotech

Synthetic biology hinges on the ability to build biological systems from the bottom up using biological parts. Plasmid design is crucial and with so many parts to choose from, assembling compatible parts can be a bottleneck in Syn Bio workflows. To address this, Explora Biotech have recently launched Double Helix Technologies (DOULIXTM) – a toolkit to design, validate and synthesise custom constructs for synthetic biology.

This is a 3-step process:

1.      Design. Using their free online design platform, users can design a custom plasmid from their library of parts (‘biomodules’) or from your own custom sequence to assemble into a vector of choice.

2.      Validation. The software guides you through a design validation to avoid common design flaws.

3.      Synthesis. You can order ready-to-use full length constructs, or order individual Biomodules to assemble yourself.

It looks good on paper, so we got in touch with Davide De Lucrezia from DOULIX to find out more.

 

Q. What do you think are the current bottlenecks of synthetic biology projects?

We feel that the lack of in vivo standardization of standard biological parts is the main bottleneck. Without reliable in vivo data, any simulation will run on wobbling data and will inevitably be of little help to experimental synthetic biologists.

 

Q. How does DOULIX aim to circumvent these issues?

We started a challenging project to measure in vivo activity of most commonly used standard biological parts called DOULIX GrandChallenge. Together with the LIAR EU project (http://livingarchitecture-h2020.eu/) we aim to provide the SB community with rock-solid in vivo data to be used for simulation and model refinement. These data will be available through DOULIX’s database and used by our multiscale simulation platform to be released in 2018. Together with our synthesis platform, we hope to provide the SB community with a comprehensive toolkit that allows them to move seamlessly from design to fabrication.

 

Q. What is the average turn-around time for de novo constructs from DOULIX?

Individual dsDNA can be delivered in as little as 5 working days and full-length circular constructs of up to 10 kbp are usually delivered in 15 working days.

 

Q. Are the Biomodules all optimised for E. coli, or are other (and if so which?) expression systems catered for?

To date, most of our Biomodules are optimised for E.coli chassis. However, we are glad to announce to EUSynBioS a new partnership with Agilent that will tremendously expand our Biomodule collection to include parts optimised for Yeast and mammalian cells.

 

Q. What is the advantage of DOULIX over designing constructs ourselves?

With DOULIX you can finally use in vivo validated Biomodules so you can focus on construct/circuit design rather than part validation. I think that DOULIX is a substantial step ahead toward abstraction and decoupling in SB, something we really need if we want to unlock the full potential of SB.

 

Q. How do you see DOULIX expanding to serve the Synthetic Biology community in the future?

The next big thing is our DOULIX simulator, an integrated simulation platform for multiscale modelling using in vivo data. We expect it to have a big impact on the SB workflow. Yesterday we used the old genetic engineering approach of trial-and-error, today we are using the Synthetic Biology approach of design-build-test. But as for tomorrow we envision a time when we will confidently simulate before we built, saving time, money and delivering safer drugs, greener products and greater knowledge. Tomorrow, we envision the dawn of constructive biology.

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DOULIX are kind sponsors of EUSynBioS. For more information about Explora Biotech and DOULIX, visit https://www.explora-biotech.com/ and https://www.doulix.com/ or contact info@doulix.com.

10,000 Genes for the Synthetic Biology Community: Twist Bioscience Partners with the BioBricks Foundation

With exponential discoveries taking place every day, we are in an exciting era of biology as researchers unlock the potential of DNA.”

Emily M. Leproust, Ph.D., CEO of Twist Bioscience

 

"Most of biotechnology has yet to be imagined, let alone made true.”

Drew Endy, Ph.D., associate professor of bioengineering at Stanford University and president of the BioBricks Foundation

 

As Synthetic Biology leaps forward from its infancy into its formative years, we’ve seen the price and time of DNA synthesis dropping to the extent that we are now rarely constrained by availability of the ‘parts’. As Prof. Endy alludes to, our greatest roadblock will soon be the limits of our imagination. Twist Bioscience’s (www.twistbioscience.com) recent partnership with the BioBricks Foundation (www.biobricks.org) is a major step forwards towards this vision. The partnership aims to make 10,000 genes freely available to the research community – with us as the SynBio community suggesting which genes should be made. Once built by Twist Bioscience, the genes will be shared with the community by the BioBricks Foundations. This represents the first time that multiple genome-equivalents of synthetic DNA will be made available at no cost to the research community – a major milestone for Synthetic Biology.

We got in touch with Emily Leproust, CEO of Twist Bioscience to find out more.

 

Q. Synthetic Biology is a very fast moving field – how do you think the challenges now compare to 5 years ago?

Five years, ago, synthetic biology required painstaking work to achieve results. Synthesizing DNA could only be done in the smallest of quantities. Gene editing was held back by a myriad of technical and biological impediments.

Since then, Twist Bioscience has changed the way DNA is synthesized. Our silicon-based manufacturing process has led to cost-effective, rapid, high-quality and high throughput synthetic gene production. This, in turn, expedites the design, build and test cycle in many industries – pharmaceutical and biotech, industrial chemicals, agricultural biotech, academia and even digital data storage.

In addition, the discovery of the CRISPR gene-editing technique, with its ability to guide precise, directed changes to genomic DNA is making it much easier for researchers to manipulate DNA. They can now cut sequences and repair DNA where needed. Thus, the process of gene editing has become easier and cheaper. The emergence of CRISPR has ushered in a new era of genetic investigation.

The challenge going forward is to leverage the great potential that these technologies offer us to continue to develop breakthroughs in fields such as personalized medicines, pharmaceuticals, sustainable chemical production, improved agriculture production, diagnostics, DNA data storage, and more. We’ve already seen incredible advances with coats and shoes now made from spider silk, tires and carpet made in sustainable ways, new methods of food production, and I believe we’ve only seen the tip of the iceberg.

 

Q. What is the rough timeline for this project – when will the genes will become available to the research community?

The BioBricks Foundation will moderate a free and open online forum that allows researchers anywhere to suggest which genes should be built. Genes gaining enough "up votes" that are determined to be of public benefit may then beprioritized for selection by BBF. Twist Bioscience will manufacture the genes for BBF. Twist Bioscience has already received and manufactured the first order of genes.

 

Q. Is the project designed to span SynBio in a range of host organisms, or will it be focusing on genes for mammalian/ yeast/ bacterial expression systems?

Suggestions for gene use can come from all fields of biology.

 

Q. What is your vision for Synthetic Biology 10 years from now, and how are can Twist Bioscience help us get there?

I believe that synthetic DNA can improve sustainability by making products in a different way - for example, we can make plastics today without starting from the petrochemicals in oil, by using yeast or e.Coli to create the same materials. Also, synthetic DNA already has, and will continue to, play an important role in the development of new medicines, diagnostic tools and precision therapeutics. The third area of tremendous importance is food safety.  With synthetic biology, there are ways to drastically improve food security by engineering both crops or even the symbiotic bacteria in the soil to benefit all. This could play a role in the developing world as well as the United States, Europe and Asia.  

Overall, the ‘50s were about aerospace (satellites, planes), the ‘70s about semi-conductors, the ‘80s about computers, the’ 90s about software and ‘00s about the Internet. We are now in the biology era, and biology and specifically synthetic DNA will have a massive impact and create tremendous value. At Twist Bioscience, we provide the material necessary to accelerate research and look forward to playing a key role in this exciting time.

 

 

Twist Bioscience are a kind sponsor of the EUSynBioS annual Symposium in Madrid 31s August – 1st September. For more information on the partnership with the BioBricks Foundation, visit www.twistbioscience.com or www.biobricks.org.

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Emily Leproust

CEO and Founder, Twist Bioscience

Geoengineering and synthetic biology

This September, as part of our annual symposium, EUSynBioS will hold an Open Discussion on the topic, "Synthetic Biology and Environmental Engineering", at the National Center for Biotechnology, Madrid, Spain. We will host experts in the field to talk about the science and the more difficult aspects of public acceptance and bioethics surrounding geoengineering and synthetic biology. 

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Geoengineering is a word that means many things to many people. Formally defined as the "deliberate intervention in the climate system to counteract man-made global warming", for some scientists it represents a cheap and effective way to protect our planet from the ravages of climate change. To others it's symptomatic of technological hubris: a grand, doomed plan to control every aspect of our ecosystem. Dig past the rhetoric though and you find a science that's still in infancy, being developed by scientists around the globe, almost as a last resort in the (now very possible) event that on-going efforts to avert climate catastrophe by reducing global emissions fail.

Current research on geoengineering is focused on either removing carbon dioxide from the Earth's atmosphere or reducing global warming by reflecting more solar radiation away from the planet. Most proposals to achieve these goals rely on physical engineering solutions, cloud seeding for instance. A more expansive reading of "geoengineering"though, leads to several intriguing ideas on using synthetic biology to remedy the effects of intensive industrialisation/pollution on the environment.

i. pale blue dot

In 1980, the US Supreme Court issued a ruling that changed the status of living organisms forever. In Diamond v. Chakrabarty the court affirmed the right of inventors to patent living organisms that had been modified for some purpose. In this case, the patent was granted to a genetically engineered creature called the Superbug. The Superbug was a strain of Pseudonomas putida that could break down crude oil, and was posited as a tool to deal with oil spills. Since then, there's been a lot of work in developing such organisms, spawning a field of science called bioremediation that seeks to undo the damage human industry causes the environment. 

Now, a group of scientists are advocating the use of such organisms on a global scale to help mitigate the effects of climate change. Their, very SciFi-ish, ideas include: modifying particular species of bacteria that exist in harsh environments like deserts and equipping them with water harvesting capabilities; releasing entire stretches of DNA into a biosphere and allowing them to spread, equipping any host creature with water/temperature sensing capabilities, or releasing bacteria into the oceans that can cause pieces of plastic to stick to each other, solving the scourge of microplastic pollution. 

biologists are ever-aware of the conceit involved in predicting biological futures

These and other ideas find few takers though, and carry some real risks. We would have to be prepared to deal with the fact that any man-made bacteria released into a particular part of the world might escape a particular ecosystem, potentially wreaking havoc in others. Biological entities evolve, and evolution might change released modified bacteria in unpredictable ways. 

These are concerns synthetic biologists are tackling head on. In the last five years, we've made tremendous progress in engineering 'kill-switches' that could allow us to precisely control engineered bacteria in natural ecosystems. We've also developed bacteria which have been so extensively engineered that they cannot interact with other life-forms very well, or cannot reproduce, hence limiting the potential spread of synthetic DNA. Yet, biologists are ever-aware of the conceit involved in predicting biological futures and for the moment these bacteria will remain in petri dishes in labs around the world. 

ii. the red planet

The largest concern with biological geo-engineering is the fact that we might cause dangerously irreversible changes to the only habitable planet we know of. This is why, a group of scientists including NASA researchers are exploring biological options in terraforming Mars. The hopes are many, ranging from making Mars human-habitable (paving the way for eventual human colonisation), to using the red planet as a test-bed for ecosystem engineering whose lessons might then rescue the Earth from climate catastrophe. Less futuristic scenarios include the possibility of employing bacteria to harvest resources directly from Mars, or recycling consumable resources like waste-water, making manned Mars-missions a cheaper and easier endeavour. Most experts agree though that terraforming, the process of completely changing Mars' atmosphere is a process that could take centuries. A nearer-term option is something called para-terraforming. Paraterraforming envisions making smaller, enclosed spaces on Mars habitable for humans. Previous experiments in paraterraforming conducted on Earth have met with little success; however the prospect of engineering organisms specifically for terraforming makes this a more feasible proposition. 

Some however, question the ethics of using Mars as a lab-bench. One argument is that any human attempt at terraforming Mars might destroy or alter any remnant, hitherto undiscovered life on the planet. Another, that seeding Mars with terrestrial life may change a potential independent development of biological life on the planet in the distant future. These are minority opinions however. A view that, in my opinion, holds more merit suggests that the creation of Mars as a back-up planet might hinder attempts to mitigate anthropogenic climate change and pollution here on Earth.

iii. a last resort

There are two forms of climate change mitigation on the table at the moment, passive and active. Passive mitigation uses methods that are easier to swallow for most, reducing global consumption, stricter pollution controls, and switching to low-carbon sources of energy. The problem however lies in the fact that passive mitigation alone might not be enough to limit global warming to the 2°C threshold set by the Paris Agreement. Indeed, experts are highly sceptical that limiting warming to even 4°C is feasible given current trends. And the difference between a 2°C and 4°C limit is that the latter will result in massive droughts, flooding on an unprecedented scale and food shortages.

In this scenario, several climate experts have called for more drastic measures including non-biological geoengineering technologies cloud-seeding. In fact some estimates claim that cloud-seeding on a large enough scale might even bring global temperatures down to below pre-industrial levels. In this scenario then, would we even need a biological solution that might carry more risk? 

A possible benefit of biological remediation is of course that we might be able to rescue ecosystems that are on the brink of collapse, something that physical solutions like cloud seeding might never be able to achieve. Biological solutions can address biological problems in a manner that purely physical measures might struggle to. Another aspect of synthetic biology, the de-extinction of extinct species, is something that might supplement the reduction in global warming with the restoration of lost biospheres. 

On the policy front geoengineering is a topic that's often scoffed at or neglected in favour of discussions such as emissions reduction. The reasons for this are legitimate, though given the current political climate with the US backing out of climate accords, the dream of a 2°C reduction in global warming seems to be growing ever more distant. Science agencies across the world are waking up to this fact, and just a couple of months ago China announced the world's largest geoengineering research program. As of now, geoengineering remains a last resort, and biological measures even more so.

This isn't stopping scientists from experimenting with it though, and nor should it. 


Written by: Devang Mehta
Devang is currently a PhD student in Plant Biotechnology and Science & Policy at ETH Zurich. He also serves on the EUSynBioS Steering Committee as Policy Officer. Follow him on twitter at @_devangm or check out his blog at www.devang.bio

Photos: All photos used under CC0 license. 

iGEM 2017 UCL: Light Induced Technologies (LIT)

Using light in the future will mean more than illuminating rooms and flash photography. This year, a team of 9 undergraduates from UCL, with academic backgrounds ranging from Biochemical Engineering to Psychology, are shaping this vision. The members, coming from anywhere between Mexico and Luxembourg, will use the world’s largest synthetic biology competition at MIT, iGEM (international Genetically Engineered Machines), as a platform to develop light induced technologies.

The goal is to make synthetic biology more accessible to the general public by providing standardised and easy-to-use light control systems

LIT (Light Induced Technologies) - and no, it’s not Elon Musk’s new company - came out of a two-day project hackathon back in June. Ideas ranged from bio-robots to improve survival chances and collect data on Mars, to using optogenetics to control gene circuits. “The goal is to make synthetic biology more accessible to the general public by providing standardised and easy-to-use light control systems” – the team`s stated vision. The potential applications range from medicine to fabrication. The cells are engineered to respond to light in a tightly controlled manner. This switch can then be coupled to a wide variety of biological processes.

In essence, organs are made out of complex networks of different mammalian cells. To gain control over that complexity, LIT will use light to induce cell adhesion and trigger genetic networks in specific parts of the cell population. This work will be done in pluripotent stem cells. Their work is the first steps towards building organs from digital blueprints and tissue regeneration.

Stereolithography is an important technique in engineering and prototyping. The team aims to produce an organic version of this 3D printing method by allowing bacteria to form 3D structures through cell adhesion. Once this is implemented, specific wavelengths will be tested to produce biopolymers that are UV-resistant and environmentally friendly. Light induced technologies are also trying to optimise a bioluminescence system to create an efficient bacterial lightbulb.

This interdisciplinary project is based on research and mathematical modelling. However, other components such as entrepreneurship and public engagement will also contribute to its success. Research and engineering doesn’t happen in a bubble, so one must acknowledge and involve a wide variety of actors. The team has been working with different non-academic stakeholders in the project. For example, talking to architects has shaped the vision of what can be done with biopolymers in the field and inspired design. The planned activities over the summer aim to get people excited about synthetic biology, communicate science effectively and assimilate the ethical and societal implications of the projects.

There is an easy answer to the ‘so… what happens next?’ question. The website and social media pages (see below) are platforms for both communication and feedback on the project. Until November, you can get in touch, offer suggestions and collaborate.

Facebook: UCL iGEM

Instagram: ucl_igem17

Twitter: @ucligem

Website: http://2017.igem.org/Team:UCL

 

YEBN'S 2nd Round Table

Our friends at the Young European Biotechnology Network hold their second round table event this September, join them!

YEBN'S 2nd Round Table is going to take place in Frankfurt, Germany. When? Saturday 9th of September.

Here you could find an exciting one day program to exchange between different local and national life sciences organization within Europe in terms of activities and structure (sponsoring, working groups etc). We will also inform you about European supporting programs such as Erasmus +.

Are you a member of a life science organization within Europe? We are looking forward to your application: eb@yebn.eu