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Dr. Darren Nesbeth

lecturer in Synthetic and Molecular Biology at the University College of London and member of the European Federation of Biotechnology (EFB)


Synthetic Biology in Europe is a broad church, as evidenced by the range of speakers and content presented at the first Applied Synthetic Biology in Europe  conference (ASBE 2012) 6 to 8 February this year at Barcelona.

Organized by the EFB, this conference brought together for the first time Europe's leading academics and industrialists who are working to take Synthetic Biology out of the laboratory and into the boardroom.

So what is Synthetic Biology? Although definitions abound, it is generally agreed that Synthetic Biology is a new scientific discipline that aims to apply engineering concepts to making new, useful biological tools. A critical engineering concept in Synthetic Biology is standardization. Standardization of components was a major factor in the growth of the Industrial Revolution in the 18th and 19th centuries, as engineers and inventors of the time benefited from using compatible (hence interchangeable) materials and design standards. In a similar fashion, Synthetic Biologists today also seek to standardize the design, assembly, use and measurement of biological components. Interchangeability allows everyone to benefit from a larger component toolbox and often entails a simplified, modularized design that lowers the technical barriers to entry for non-specialists.

The highest profile examples of Synthetic Biology in action include the first-ever nucleus transfer experiment using entirely chemically synthesized DNA and the development of cheap anti-malarial drugs by assembling genes from multiple sources into a single modified production organism.

But how do such academic achievements translate into the economic growth and jobs so badly needed in the current financial crisis? Industrial speakers at ASBE 2012 from companies such as Icon Genetics (Germany) and Novozymes (Denmark) suggested some ways forward. Dr. Sylvestre Marillonnet of Icon Genetics outlined how his company is developing DNA assembly technologies that could be automated and hence possibly benefit from robotic platforms to increase the speed, efficiency and predictability of constructing and improving biological tools. The impact of European regulation on the commercial partnerships that will ultimately form the value chains of a mature European Synthetic Biology sector are of particular importance to companies such as Novozymes that are seeking to grow Europe's biotechnology capacity.

The pharmaceutical industry, a traditional strength in Europe, was also represented at ASBE 2012 in the form of sponsorship from the Centre for Innovative Manufacturing in Emergent Macromolecular Therapies based at University College London (UCL) UK and supported by the UK Engineering and Physical Sciences Research Council. Part of a collaboration between UCL, Imperial College London, London School of Pharmacy and 24 companies, the aims of the Centre are philosophically aligned with Synthetic Biology as it seeks to develop statistical and computational techniques to integrate the design of macromolecular biological medicines with manufacturing operations and business economics.

Several academic speakers at ASBE 2012 also presented research on using Synthetic Biology to improve the manufacture of next-generation biological medicines (biologics). From a Synthetic Biology standpoint, popular industrial host cells instructed by recombinant DNA to make a biological medicine can be regarded as miniature factories, each encased in a biological chassis. By re-designing both the chassis and the factory, Synthetic Biology can address the pressing global demand for cheaper biological medicines.

The yeast Pichia pastoris is a promising host chassis for producing biological medicines as it can be grown quickly and cheaply. Pichia pastoris has also been successfully instructed, again using recombinant DNA, to make proteins with the same carbohydrate attachments that occur in human cells. Among the many excellent talks on the topic of Picha pastoris, Dr. Pau Ferrer (Autonomous University of Barcelona) demonstrated how a system’s approach to analyzing large DNA transcription data sets revealed genetic factors influencing protein secretion from the host cell that would not have been immediately obvious. The performance of the cell membrane synthesis pathway was shown to be such an influencer of cell secretion and modifications of this pathway resulted in double the yield of secreted product. Professor Anton Glieder (Austrian Centre of Industrial Biotechnology) also presented work on the development of entire libraries of genetic switches (promoters) that do not occur naturally but have been designed and synthesized to provide control and performance that enhance the industrial usefulness of Pichia pastoris going forward.

Escherichia coli, the workhorse of biotechnology ever since the seventies, has also undergone significant re-engineering in the Synthetic Biology era. I was honored to present my own research at ASBE 2012 on an Escherichia coli strain engineered with disruption-actuated DNA autohydrolysis activity, in collaboration with UCB (Belgium). On an industrial scale, release of intracellular recombinant biologics from Escherichia coli cells is commonly achieved by physically disrupting the cells. This results in high levels of viscosity, plasticity and DNA contamination in the disrupted material due to release of high molecular weight genomic DNA from the disrupted cells. High viscosity and DNA contamination levels significantly impact subsequent manufacturing steps and can make a major contribution to the cost of producing a particular biologic. We engineered an Escherichia coli host strain to express a toxic nuclease protein safely in the periplasmic space where it had no access to host genomic DNA. This engineered strain grew normally on an industrial scale and, critically, still produced the recombinant biologic at the same, or higher, levels as the non-engineered strain. Upon cell disruption, all large genomic DNA molecules were degraded within minutes with no need for additional co-factors or buffering.

Excellent science was presented throughout ASBE 2012, ranging from advanced computer modeling, plant molecular biology, metabolic engineering and nanoencapsulation to bioethics and protein evolution. This short article cannot hope to do justice to all the contributions, including innovative public engagement videos and the warmest of welcomes to the beautiful city of Barcelona. The best way of getting a closer view of Applied Synthetic Biology in Europe is to attend the next conference!

On a serious final note, the longer the practical impact of Synthetic Biology is absent from the media, the more newsworthy it will be to label the discipline as either over-hyped or dangerous (or both, as the range of opinions held across large numbers of people are often contradictory). The practical achievements and benefits of the work presented at ASBE 2012 will hopefully help positively impact sentiment toward Synthetic Biology across a range of general publics throughout Europe and beyond.

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