Science - June 21, 2015

Synthetic biology is in the picture

Albert Sikkema

Wageningen UR is going to be investing in synthetic biology, one of the investment themes mentioned in the strategic plan. This is a new discipline, in which researchers rebuild and design bacteria for industrial purposes. Professor Martins dos Santos, who recently acquired two large EU projects, will write an action plan.

Last year a group of Wageningen students came up with a weapon against the dreaded Panama disease which is attacking banana plantations all around the world. For iGem, a synthetic biology competition for students, they adapted a soil bacterium so that it would specifically target and disable the soil fungus Fusarium oxysporum. This fungus causes Panama disease, which infects bananas and causes millions of euros’ worth of damage every year. In order to switch off the fungus, the students took a sensor from another soil bacterium which is immune to Fusarium. When this sensor detected the banana’s enemy, a few genes in the soil bacterium were activated which produced fungicide. This stopped the growth of the pathogen. 

Vitor Martins dos Santos, professor of Systems and Synthetic Biology, wants more of these kinds of projects in Wageningen. Together with Dirk Bosch of the Plant Sciences Group, he heads the investment theme Synthetic Biology, to which the executive board has allocated extra funding for the coming years. Martins dos Santos will write an action plan outlining how he wants to embed this new discipline in Wageningen research and education. 

The Portuguese professors talks about bacteria as though he were talking about cars. He takes a bacterium (such as the Pseudomonas putida which the iGem students used) and aims to strip it down to the chassis, as it were. Then he seeks to build up the bacterium again using spare parts (in this case DNA) to end up with the bacterial equivalent of a custom-built sports car, truck or station wagon. To achieve this, he needs to know exactly how the bacterium works (systems biology) and how he can redesign and influence that system so that the bacterium does exactly what he wants it to do (synthetic biology).

This new field, he explains, is based on several different disciplines. ‘We used to simply cultivate useful bacteria, such as the one which make bio-ethanol. The trick was to create optimal conditions for the bacteria. Then came genetics, and it became possible to link genes to certain functions of the organism. But that gives a fragmented picture, with very many genes and functions, so that you cannot see the wood for the trees anymore. So then we started using disciplines such as genomics, proteomics and metabolomics, and mathematical modelling, to identify the relations between the trees. By connecting parts and gaining an understanding of the interactions between them, we actually find the structure of an organism. That is systems biology: how does a biological entity work?’ Martins dos Santos worked in this field at a German institute for 10 years.

Synthetic biology builds on systems biology. ‘Once you understand the biological system, you can create a design, and model and influence the system. That is a bit different to genetic modification, in which you cut and paste a few genes in the DNA to get a desired characteristic. With synthetic biology you aim to design a new bacterium which does exactly what you want it to do. That is engineering.’

The aim of synthetic biology is to design a new bacterium that does exactly what you want it to do.
Martins dos Santos

The Rathenau Institute describes synthetic biology as ‘a new form of biotechnology, where the modification of existing, natural forms of life gradually transforms into the targeted engineering of new, synthetic forms of life.’ Because it is a young discipline, there are still no products of synthetic biology on the market. There are some research results, however. For instance, the biomedical company DSM has redesigned the fungus Penicillium notatum so that it can manufacture a certain group of antibiotics. Likewise, Martins dos Santos is focusing on redesigning existing biological systems so they can carry out particular tasks.

Wageningen is in a good position to apply this field of fundamental research in an industrial setting, says Martins dos Santos. He himself has just brought in two EU projects in which he will be working on adapting two bacteria. In the MycoSynVac project he will be working on the pathogenic bacterium Mycoplasma pneumonia. A lot is already known about this bacterium, especially at the Centre for Genomic Regulation in Barcelona, the Spanish partner in the project. Different variants of this bacterium cause disease among chickens, cows, horses and humans. The researchers want to strip down the bacterium so that all the specific genes and proteins involved in infecting victims are removed, leaving only the ‘chassis’, an organism which can provide the basis for several vaccines against Mycoplasma. ‘Our contribution in Wageningen is that we create a design for this chassis and model it using building blocks. We need models in order to understand the processes in bacteria.’ The great thing about Mycoplasma is that it only contains 500 genes and proteins. ‘We are starting with a small organism.’

Martins dos Santos talks about bacteria as though he were talking about cars: strip them down to the chassis.
Martins dos Santos

The bacterium in the second EU project, Pseudomonas putida, has a genome that is 12 times bigger but has not been studied as thoroughly as Mycoplasma. P. putida’s strong point is that it withstands stress well – a crucial characteristic in the processing industry. It is also a broad-spectrum catalyst for chemical processes such as those used to extract fuels or chemicals from biomass. But that production is not efficient or selective enough, so production with this Pseudomonas is not economically viable. By stripping and reconstructing the soil bacterium, Martins dos Santos hopes to improve production. He also wants to use mathematical modelling to produce made-to-measure P. putida products. ‘This little bug can work eight times more efficiently, for instance, to produce a substance that is a precursor of nylon. We have already demonstrated that.’ He expects applications in the production of organic crop protection materials, drugs and biofuels. 

Martins dos Santos is already collaborating with the Microbiology, Applied Mathematics and Bioprocess Engineering chair groups, The Applied Metabolic Systems, Biometris and Bioscience DLO groups, and Rikilt. These partners collaborate in the Wageningen Centre for Systems Biology (WCSB). In future he would like to collaborate with many more biology-related groups, as well as with social scientists working on the ethical aspects of this technology. He wants to set up an industrial platform for externally financed research. He also hopes to be able to inject his conceptual perspective on biology into more of Wageningen’s degree programmes. ‘In all biology you need to understand the concept of networks, of parts which display new forms of collaboration and coherence, as both social media and living organisms do. That conceptual way of thinking, for which you need mathematics, is a feature of the new biology. We are keen to introduce that into the educational programmes.’ The frontrunners have already gone into action – in the iGem competition for synthetic biology, for instance.