We are a multidisciplinary international team of nine academic and industrial partners.
By our cooperation we fill major technical and scientific gaps to allow a full-fledged application of contemporary synthetic biology to large-scale industrial biotechnology in Europe.
Centre for Systems & Synthetic Biology (WCSB)
Wageningen, The Netherlands
The Wageningen University (WU) is an internationally leading education and research organisation. As a part of its strategic plan, the WU has set Systems & Synthetic Biology as one of its spearheads, having established in 2010 the Chair of Systems and Synthetic Biology and, in 2012, the overarching Wageningen Centre for Systems & Synthetic Biology (WCSB). The department of Systems and Synthetic Biology contributes to the elucidation of the mechanisms underlying basic cellular processes, evolution and interactions among microbes and between microbes and their environment and to translate this knowledge into applications of biotechnological, medical and environmental interest. WCSB, set up to coordinate all systems biology activities at Wageningen University, will be the primary cooperation partner for research centres and industry in this specialist field. The WCSB’s research focuses on the entire spectrum of biological systems, from DNA to ecosystem, and involves topics relevant to plants, digestion and microbes. Both are headed by Prof. Martins dos Santos. read more
Prof. Dr. Dipl.-Ing. Vítor Martins dos Santos, Chair of Systems and Synthetic Biology and Head of the Wageningen Centre for Systems & Synthetic Biology is also the president of the Dutch Society of Biotechnology (NBV). His lab develops and applies theoretical frameworks supporting experimental research towards the systems level understanding of the hierarchies and dynamics of cellular networks. These frameworks are used for directed cellular reprogramming, with applications to health and industry. The lab has made acknowledged contributions to large-scale genome engineering of designer microbes and to cellular-reprogramming.
Nhung Pham MSc
Ruben van Heck MSc
Linde Kampers MSc
Stamatios Damalas MSc
The missing link between computer and laboratory
Model-driven metabolic engineering of Pseudomonas putida
Microscopic animals called microorganisms are used to produce diverse products, including, but not limited to, food additives, antibiotics, vaccines, bioplastics, bio-pesticides and biofuels. Often, the use of microorganisms enables a much greener, faster and cheaper alternative to produce products in high volumes than conventional chemical processes. Each species of microorganism used has its own benefits, but also downsides. With the techniques we now have available, it is possible to choose the ideal candidate, and then improve it so that it has little to no downsides.
Within our EmPowerPutida project, we have chosen for Pseudomonas putida as the best candidate. It can withstand much stress, which will allow it to flourish and produce more than other bacteria on a large scale. It is also able to adapt quickly to new surroundings. To top it off, Pseudomonas putida is Generally Regarded as Safe (GRAS), which means it has passed extensive safety tests with flying colours.
Nowadays, this great method can be coupled to the world of computers. You can predict accurately how much effect an improvement can have. This allows for less wasting of time and money than if all ideas are directly tried in the lab. The results gathered at the lab can in turn be used to improve computer predictions. Often, within an organisation, there is only a limited amount of people proficient with making the computer predictions, opposed to many who experiment on the lab.
At Wageningen University & Research, the Systems and Synthetic Biology group, headed by Prof. Dr. Ir. Vitor Martins dos Santos, we go beyond just small-scale collaborations. Instead, we focus on building highly interactive bridges between dry computer predictions (dry lab) and wet laboratory experiments (wet lab). The number of dry lab workers is about equal to the number of wet lab workers. This allows for us to apply predictions where they haven’t been applied before, finding new solutions to yet unsolved problems. This close collaboration between people also enables the direct and fast exchange of new results gathered on the lab to feed back into the predictions, a process which can otherwise take months.
Within an eternal feedback loop, we use the information gained from metabolic models to optimize experimental setup, and use experimental data to improve the existing models. By combining these two techniques, we show that the sky is the limit. Within the EmPowerPutida project, we improve Pseudomonas putida in many ways to increase its potential as the workhorse for biocatalysis on an industrial level.
The state-of-the-art tools and methods in systems biology provide opportunities to understand and redesign the metabolism of Pseudomonas putida. In the EmPowerPutida Project, we use genome scale metabolic models as a platform to design metabolic engineering strategies for the production of native and non-native compounds in Pseudomonas putida. In silico (dry lab) tools are used to pinpoint possible targets for gene knock-out, knock-in or other genetic modifications that overcome bottlenecks in biochemical production processes. This results in a change of metabolic fluxes from growth to production. The in silico design is then implemented in the wet lab.
At the wet lab, implementation includes improvement and further development o
f a plug-and-play synthetic assembly system to edit the Pseudomonas putida genome, but also includes combining gene insertion with evolutionary pressure to increase its tolerance to grow under multiple different conditions. An example of this is increasing the bacterial survival rates under low oxygen conditions.
The question is not what we at Wageningen UR do to empower Pseudomonas putida. The question is how you would like to empower it!
The Wageningen EmPowerPutida team. From left to right: Linde Kampers MSc, Ruben van Heck MSc, Nhung Pham MSc, Stamatios Damalas MSc and Prof. Dr. Ir. Vitor Martins dos Santos.
Institute for Biochemical Engineering (IBVT)
The Institute of Biochemical Engineering (Institut für Bioverfahrenstechnik, IBVT, University of Stuttgart) is focused on bioprocess development based on systems metabolic engineering and synthetic biology. Microbial and mammalian cells are studied thoroughly applying metabolomics and mRNA analysis for modelling and model-based strain development.
As such novel production platforms (e.g. for Escherichia coli) are created and further elaborated as new microbial producers. The interaction of global regulatory networks is elucidated while mirroring large-scale production conditions. Reasons and consequences of population heterogeneity – especially occurring under large-scale stress conditions – are unraveled. read more
Prof. Dr.-Ing. Ralf Takors
Prof. Ralf Takors is heading the IBVT since July 2009 after he had worked at Evonik Industries AG for about 5 years. There he was responsible for metabolic engineering and bioprocess development from lab- to production scale. In 2004 he had finished his 7-year lasting ‘Habilitation’ at Forschungszentrum Juelich/RWTH Aachen (Germany). Ralf is trained as a process engineer and has received Dr.-Ing. for Biochemical Engineering in 1997.
Dr. Bastian Blombach studied Biotechnology at the University of Applied Sciences Weihenstephan with internships at Creatogen AG and Boehringer Ingelheim (Vienna). During his Ph.D. he worked at the Institute of Microbiology and Biotechnology of Ulm University. Since 2012 he is junior group leader of the ‘Molecular Biotechnology’ group at the IBVT.
Institute of Technical Biochemistry (ITB)
The Institute of Technical Biochemistry at the Universitaet Stuttgart is led by Prof. Dr. Bernhard Hauer and covers biocatalysis, functional biomaterials, molecular biotechnology, fermentation and bioinformatics. The interdisciplinary research focuses on the cloning, expression, characterization and optimization of enzymes including P450 monooxygenases, lipases, enoate reductases, dehydratases and cyclases. Methods of laboratory evolution are used to generate novel and improved biocatalysts for industrial applications. The laboratories are equipped to implement analytical chemistry, microbiology, protein biochemistry and molecular biology. The research requires contributions from many disciplines, including chemistry, biochemistry, molecular biology, microbiology, bioengineering and bioinformatics. read more
Prof. Dr. Bernhard Hauer
Prof. Dr. Bernhard Hauer has spent most of his career in industry working for BASF SE in Ludwigshafen, Germany, where he led the white biotechnology efforts. He has a strong background in this field and brings insights into industrial research and process development. He is the author of more than 200 articles and patents covering various topics of biotechnology and specialised areas. Since 2009 he is the head of the Institute of Technical Biochemistry at the Universitaet Stuttgart, Germany. He has been awarded with the BASF Award for Innovation of BASF SE (1997), the Dechema Award of the Max Buchner Research Foundation (2003) and the Biocat Award (2004).
Consejo Superior de Investigaciones Científicas
The Spanish National Biotechnology Centre (Centro Nacional de Biotecnología, CNB) is ascribed to the Spanish National Research Council (Consejo Superior de Investigaciones Científicas, CSIC). At present, the CNB is the biggest research centre of the CSIC. The CNB stands out for its multidisciplinarity and encompasses two major scientific-technical areas within the CSIC. The centre’s departments of Macromolecular Structures, Cellular & Molecular Biology, Microbial Biotechnology and Immunology & Oncology belong to the area of Biology and Biomedicine; the department of Plant Molecular Genetics covers the area of Agricultural Sciences. In addition, a transversal Systems Biology Programme was initiated in 2009 with the vision to interconnect both areas. read more
Prof. Dr. Víctor De Lorenzo
Professor of Research of the National Center of Biotechnology of the Spanish Research Council (CNB-CSIC) in Cantoblanco-Madrid (Spain). 325 Scientific publications at this time. Member of the Editorial Board of The Journal of Bacteriology (1989-2004). Member of the Editorial Board of Environmental Microbiology (1999-2008). Member of the Editorial Board of FEMS Microbiology Ecology (1998-2002). Member of the Editorial Board of Microbiology UK (mid 1999-2004). Member of the Editorial Board of Biodegradation (2001-2003). Member of the Editorial Board of Microbial Biotechnology (since 2008). Editor-in-Chief of Current Opinion in Biotechnology (since 2008). Member of the Editorial Board of Current Opinion in Microbiology (since 2008) Member of the Editorial Board of BioEssays (since 2009). Molecular Microbiology and Biotechnology. Genetic tools for Gram-negative bacteria destined for environmental release. Biodegradation of xenobiotic compounds. Environmental applications of recombinant antibodies, Synthetic Biology and Systems Biology. Metals in prokaryotic systems: Iron transport, resistances to heavy metals and metalloadsorption. Gene expression in Gram-negative bacteria, with focus in Pseudomonas. Regulation of catabolic pathways. Design of transcriptional factors and regulatory circuits á la carte.
Eidgenoessische Technische Hochschule Zuerich
ETH Zurich is one of the premier European research universities with an outstanding research record (including 21 Nobel laureates connected to it) and a current complement of 400 professors. Key strengths of the university are in life sciences, chemistry, engineering, and computer science. The Department of Biosystems Science and Engineering (D-BSSE) of ETH Zurich in Basel was founded in 2009 to lead a unique interdisciplinary research initiative on the interface of life sciences and engineering with two strategic thrusts, Synthetic Biology and Systems Biology. Its core conceptual thrust is to explore and engineer molecular networks in biology and biotechnology on a systems level concomitantly with the required overarching conceptual and technological developments. read more
Prof. Dr. Sven Panke
Sven Panke is a Professor of Bioprocess Engineering at the ETH Zurich. After his PhD, also at ETHZ, he worked for two years in the biocatalysis group of the Dutch chemical company DSM (Geleen, The Netherlands). He returned to ETH in 2001 as an Assistant Professor, received tenure in 2007, and then moved to the newly founded ETHZ Department of Biosystems Science and Engineering in Basel. His main research topics include integrated reaction-separation systems, high-throughput screening, and synthetic biology. His work was awarded with the ETH Medal and the DSM Research Award.
Instituto de Tecnologia Química e Biológia - Universidade Nova de Lisboa
The Instituto de Tecnologia Química e Biológica (ITQB) is a research and advanced training institute of the Universidade Nova de Lisboa. Its mission is to develop high-quality research in chemistry and the life sciences, considering all levels of complexity and their potential applications, so as to contribute to the understanding of life’s mechanisms. Its highly multidisciplinary nature makes ITQB a leading centre for advanced training of researchers in Portugal. ITQB hosts a number of independent laboratories grouped in five research divisions and consisting of a scientific staff of about 400 researchers with different scientific interests and backgrounds. Researchers at ITQB benefit from outstanding facilities, equipment, and support services, some of which are unique in Portugal. read more
Prof. Dr. Cecília Arraiano
The main research area of Prof. Cecília Arraiano’s laboratory has been to elucidate determinant factors for the control of gene expression. Biological processes cannot be fully understood without a deep understanding of RNA metabolism. The main focus of the Gene Expression Lab is the study of RNA degradation mechanisms and the characterisation of enzymes that mediate RNA decay in microorganisms. Namely, ribonucleases involved in maturation, degradation and quality control of mRNAs and functional non-coding sRNAs. These studies have been applied to areas of Biotechnological interests and Health. Other research interests include bacterial stress response, cell growth and survival.
Edinburgh, United Kingdom
Ingenza: An Industrial Biotechnology Company with a broad customer base across the chemicals, pharmaceuticals, food, feed and fuel industries. We apply synthetic biology to the manufacture of industrial products including enhanced biofuels, sustainable manufacturing of chemicals and the production of protein therapeutics. Our scientific and commercial activities are led by a management team with over 25 years’ experience in applied bioscience and the development and commercialisation of biobased products.
In addition to engaging in strategic partnerships to tailor our bioprocess services for clients, we also license our proprietary bioprocess technologies. read more
Dr. Ian Fotheringham
Ian Fotheringham received a Ph.D. in Molecular Biology from the University of Glasgow, UK in 1986. He joined the NutraSweet division of Monsanto in Chicago, USA, constructing microbes to produce the Aspartame® sweetener. From 1993 he continued developing large scale bioprocesses with NSC Technologies and Great Lakes Fine Chemicals. In 2003 he co-founded Ingenza, an Edinburgh, UK, based Industrial Biotechnology SME with a unique range of proprietary enabling technologies. Now a leader in microbial strain improvement, synthetic biology, fermentation and bioprocess development, Ingenza works with industrial partners worldwide to commercialise state of the art biomanufacturing processes. Ian has published 35 papers and articles and holds 8 current patents.
LifeGlimmer GmbH is an international science-driven company that caters advanced solutions for the full research pipeline in bioinformatics, data integration, and systems biology. From designing workflows, via sophisticated analytics and dynamic simulations, to new knowledge discovery and novel inroads to applications in both fundamental and applied biological and biomedical practice, LifeGlimmer GmbH offers tailored scientific solutions to deal with complexity in the biosciences. In addition LifeGlimmer GmbH seeks to advance scientific projects with services and consulting in project management, research strategy development, experimental design and specialised training. read more
Dipl.-Ing. François Bergey graduated in statistical mathematics. He joint LifeGlimmer GmbH in 2015. He applies his expertise in time-series RNA seq data, data mining of clinical data, text mining in medical health records and predictive modeling for experimental biology and health related science. He is also experienced in Bioinformatics, performing pathway analysis, graph search and data management of large dataset.
Mechthild Schulte M. A., has outstanding experience in business administration and public relations in international environments. As science manager in the public sector she gained profound expertise in the development and controlling of EC and nationally funded research projects. She joint LifeGlimmer Gmbh as chief administrator and involves in the cooperation of scientific and economic bodies.
Abengoa Research SL
Abengoa is a world leader in the development of innovative technology solutions for a sustainable development. Abengoa’s R&D is centralised in Abengoa Research which is a company belonging to Abengoa. The core objective is to generate knowledge and promoting its applications in the field of energy and sustainable development. Abengoa organises its research, development and innovation into the following areas: materials and nanotechnology, fluid mechanics, mechanics of solids and structures, thermal engineering, process engineering, biotechnology and biomass, and electrical networks.
Abengoa Research is developing new approaches to build synthetic pathways for biosynthesis of fuels and added-value chemicals. read more
Dr. Carlos Molina-Santiago
Dr. Carlos Molina-Santiago finished his biotechnology studies at Pablo de Olavide University (Seville) in 2010 and after that got a master degree in microbiology (Granada University). During his PhD (2010-2014) at Estación Experimental del Zaidín (Granada, Spain), he focused on the study of the biosynthesis of antibiotic compounds and the signaling mechanisms underlying antibiotic resistance in Pseudomonas putida from a transcriptomic and molecular point of view. In 2014 he moved to Abengoa Research where he is a junior researcher at the Synthetic Biology Program developing the biosynthesis of products of industrial interest using microorganisms as cell factories.
At BASF, we create chemistry – and have been doing so for 150 years. Our portfolio ranges from chemicals, plastics, performance products and crop protection products to oil and gas. As the world’s leading chemical company, we combine economic success with environmental protection and social responsibility. Through science and innovation, we enable our customers in nearly every industry to meet the current and future needs of society. Our products and solutions contribute to conserving resources, ensuring nutrition and improving quality of life. We have summed up this contribution in our corporate purpose: We create chemistry for a sustainable future. BASF had sales of over €74 billion in 2014 and around 113,000 employees as of the end of the year. BASF shares are traded on the stock exchanges in Frankfurt (BAS), London (BFA) and Zurich (AN). Further information on BASF is available on the Internet. read more
Dr. Andrea Herold
Dr. Andrea HEROLD has worked for BASF for more than 10 years. She worked in various functions in BASF’s biotechnology research and New Business Development and has a strong background in metabolic engineering. Currently, she is group leader of the Microbiology group, responsible for the development of microbial production processes of biopolymers, biological crop protection products and secondary metabolites.
Dr. Lutz Petzke is a research scientist in the Microbiology group at BASF. His expertise is the microbial production of secondary metabolites. He has more than 5 years of experience in engineering Actinomycetes and Pseudomonas strains with a strong focus on biosynthetic cluster expression.