01 04 european union research and innovation perspectives on biotechnology


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01 04 european union research and innovation perspectives on biotechnology

  1. 1. Journal of Biotechnology 156 (2011) 382–391 Contents lists available at ScienceDirect Journal of Biotechnology journal homepage: www.elsevier.com/locate/jbiotec European Union research and innovation perspectives on biotechnologyଝ Danuta Cichocka, John Claxton, Ioannis Economidis, Jens Högel, Piero Venturi, Alfredo Aguilar∗ Unit Biotechnologies, Directorate Food, Agriculture and Biotechnology, Directorate General for Research and Innovation, European Commission, SDME 8/42, B-1049, Brussels, Belgium a r t i c l e i n f o Article history: Received 1 March 2011 Received in revised form 21 June 2011 Accepted 24 June 2011 Available online 1 July 2011 Keywords: Bioeconomy Biotechnology 7th Framework Programme European Commission KBBE a b s t r a c t “Food, Agriculture and Fisheries and Biotechnology” is one of 10 thematic areas in the Cooperation pro- gramme of the European Union’s 7th Framework Programme for Research, Technological Development and Demonstration Activities (FP7). With a budget of nearly D 2 billion for the period 2007–2013, its objective is to foster the development of a European Knowledge-Based Bio-Economy (KBBE) by bringing together science, industry and other stakeholders that produce, manage or otherwise exploit biologi- cal resources. Biotechnology plays an important role in addressing social, environmental and economic challenges and it is recognised as a key enabling technology in the transition to a green, low carbon and resource-efficient economy. Biotechnologies for non-health applications have received a consider- able attention in FP7 and to date 61 projects on industrial, marine, plant, environmental and emerging biotechnologies have been supported with a contribution of D 262.8 million from the European Commis- sion (EC). This article presents an outlook of the research, technological development and demonstration activities in biotechnology currently supported in FP7 within the Cooperation programme, including a brief overview of the policy context. © 2011 Elsevier B.V. All rights reserved. 1. Introduction The European Union’s Seventh Framework Programme for Research, Technological Development and Demonstration (FP7) (European Union, 2006a), started in January 2007 and runs to December 2013. With an overall budget of D 51 billion, FP7 is divided into five Specific Programmes (European Union, 2006b): “Cooperation” (supporting collaborative research and networking); “Ideas” (which funds the European Research Council); “People” (which supports the mobility of individuals through Marie Curie actions); “Capacities” (which supports a range of actions, including Abbreviations: AAFC, Agriculture and Agri-Food Canada; CAAS, Chinese Academy of Agricultural Sciences; CSA, Coordination and Support Action; DG, Directorate General; DOE, Department of Energy; EC, European Commission; ETP, European Technology Platform; EU, European Union; FP, Framework Programme; FP77th, Framework Programme; GMO, Genetically modified organism; ICPC, International Cooperation Partner Countries; KBBE, Knowledge-Based Bio-economy; LSB, Life Sciences and Biotechnology Strategy; NEST, New and Emerging Science and Tech- nologies (2002–2006); NIH, National Institutes of Health; NMP, New Materials and New Production Processes and Devices (thematic area under FP6); NSF, National Science Foundation; SICA, Specific International Co-operation Actions; TC, Third Countries; SME, Small and Medium Enterprises; USDA, United States Department of Agriculture; WG, Working Group. ଝ This publication expresses the views of the authors and should not be regarded as a statement of the official position of the European Commission nor of its Directorate General for Research and Innovation. ∗ Corresponding author. Tel.: +32 2 296 14 81; fax: +32 2 299 18 60. E-mail address: alfredo.aguilar-romanillos@ec.europa.eu (A. Aguilar). international cooperation and support for European infrastruc- tures) and “Euratom” (comprising research and technological development, international cooperation, dissemination, exploita- tion and training activities in the field of nuclear research). The “Cooperation” programme is the largest of the Specific Pro- grammes, with a budget of over D 32 billion for the seven years. It is further divided into 10 themes (Fig. 1), which include “Food, Agriculture and Fisheries and Biotechnology” (Theme 2), more commonly referred to as the “Knowledge-Based Bio-economy” (KBBE). With a total budget of just under D 2 billion, this theme cov- ers agricultural production, fisheries and aquaculture, forestry, food quality, safety and processing, and a wide range of non-medical biotechnologies. Within this theme, the activity “Life sciences, biotechnology and biochemistry for sustainable non-food prod- ucts and processes” – further referred to as “Biotechnologies” – is sub-divided to include: • Novel sources of biomass and bioproducts: aimed at optimising the characteristics and yield of terrestrial biomass for industrial processes. • Marine and fresh water biotechnology: aimed at sustainably exploiting marine and freshwater-based biomass, either directly or as a source of novel bioactive compounds for industrial use. • Industrial biotechnology and biorefineries: originally two areas, seen more and more to converge into a single coherent framework. This examines the development and application of biotechnology for industrial processes, for both, bulk and high- 0168-1656/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jbiotec.2011.06.032
  2. 2. D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 383 Fig. 1. Budget breakdown proposed for the Cooperation Specific Programme (FP7). value speciality chemicals, typically integrating these across a biorefinery production platform. • Environmental biotechnology: covering bioremediation, micro- bial diversity and metagenomics, development of biotechnology- based eco-efficient processes and issues of genetic modification related to environmental impact. • Emerging trends in biotechnology: working on recent develop- ments and trends, e.g. bioinformatics, systems biology, synthetic biology and nanobiotechnologies. Fig. 2 provides an overview of annual research budgets spent in these 6 areas. In addition to the focus of the specific “Biotechnolo- gies” activities, biotechnology is also addressed in other Themes, for example in “Nanosciences, nanotechnologies, materials and new production technologies”, “Energy” and “Environment”. KBBE does not cover medical biotechnologies as they are included within the Health Theme. Continuing a strong basis from previous Framework Pro- grammes, the origins of the FP7 activities in biotechnology originate in the Life Sciences and Biotechnology Strategy (LSB) from 2002 (European Commission, 2002) and a conference on the Knowl- edge Based Bio-economy held in Brussels in 2005 (European Commission, 2005). These served to underline the importance of biotechnology within the development of a sustainable production system based on the use of biological resources as a replacement for fossil-based products. Research in FP7 has been at the forefront Fig. 2. Budget breakdown for Activity 2.3 “Life sciences, biotechnology and bio- chemistry for sustainable non-food products and processes” per call per area. of the development of a sustainable bioeconomy in Europe. Cur- rently, several Member States of the European Union, and other countries, are developing strategic policies on the bioeconomy. In addition, the European Commission is preparing a Communication to the European Parliament and Council on the development of a sustainable bioeconomy, due in late 2011. This will cover research and innovation issues related to developing and implementing the technologies for a successful bioeconomy, but will also go much further in order to promote the establishment of a coherent policy framework across Europe to ensure that we can take full advantage of the potential of the sector. This article presents an outlook of the research, technologi- cal development and demonstration activities in “Biotechnologies” currently supported in FP7, including a brief overview of the pol- icy context in which these actions are implemented. In certain cases and where appropriate previous Framework Programmes are referred to. The area of environmental biotechnology is emphasised as a result of its recent shift from a reactive approach (bioremedia- tion) towards a more proactive one (development of eco-efficient processes) and its importance for advances in other areas, e.g. industrial biotechnology. A number of biotechnology projects have been cited as examples throughout the article, however the selec- tion is not intended to be exhaustive. More extensive and updated information can be found on the CORDIS website (Cordis, 2011a) and in the “FP7 – Cooperation – Theme 2: Interim Catalogue. Biotechnologies Projects” (European Commission, 2010b). The leverage of biotechnology for the bioeconomy in the Euro- pean Union (Aguilar et al., 2009) and the international aspects of research programmes, and in particular links with the USA, have been recently addressed elsewhere (Aguilar et al., 2008). Therefore only a brief summary of the most pressing issues is presented here. 2. Novel sources of biomass and bioproducts (green biotechnology) Our society is using fossil resources to produce fuels for trans- portation, heating, and as a precursor for the vast quantity of essential, petrochemical products. The use of fossil resources has major limitations as both future availability and price of oil are uncertain, while their use as fuels contributes to the production of greenhouse gases. Reducing our dependence on fossil oil, by replac- ing it with carbon sourced from biomass, offers the potential to address these limitations. It is known that metabolic pathways from plants are diverse and have an inherent plasticity. Plants use sunlight as a source of energy to capture carbon dioxide for the synthesis of basic cell components. But they also synthesize a large variety of products in secondary metabolism pathways used in their defence strate-
  3. 3. 384 D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 gies or for signalling. Industry already uses a large number of these products as pharmaceuticals, cosmetics, food additives and other products. Recently, plants are starting to be used as bioreactors to produce novel proteins or bioproducts of industrial or pharmaceu- tical interest. The main advantages of plant-based production systems are flexibility, scalability and cost- effectiveness and, in the case of the plant-derived pharmaceuticals, the lack of shared pathogens between plants and mammals, which in turn constitutes a significant economic advantage. The goal of developing effi- cient molecular engineering strategies to optimise the metabolic responses and to increase yield of specific compounds (the ‘green factory’ concept) requires a profound knowledge of the complex- ity and diversity of metabolic pathways, cell biology (including intracellular compartmentalisation and of the processes control- ling gene regulation, protein accumulation and stability) and of flux control. These considerations lay at the core of the sector “Novel sources of biomass and bioproducts” within the “Biotechnologies” activity. Biomass and bio-products obtained from terrestrial organ- isms (mostly produced by photosynthetically active plants) are of key importance for the development of a sustainable bioeconomy. The first line of plant biotechnology research funded under FP7 aims to enhance metabolic pathways for novel bioproducts, and thus to reduce dependence on non-renewable petroleum-based chemical manufacturing and to provide economic and sustainable alternatives to conventional production systems. The projects are linked to the concepts of zero-waste production and biorefineries and aim to utilise plants for mass-production applications impor- tant to society at large, including the provision of inexpensive pharmaceuticals and chemical precursors. Examples include the project ICON (Industrial crops producing added value oils for novel chemicals) aiming at the development of new plant-based indus- trial lubricants; EU-PEARLS (EU-based production and exploitation of alternative rubber and latex sources); SMARTCELL (Rational design of plant systems for sustainable generation of value-added industrial products) for anti-cancer compound production in vivo, PLAPROVA (Plant production of vaccines), and METAPRO (The development of tools and effective strategies for the optimisation of useful secondary metabolite production in planta). The second line of FP7-funded research in plant biotechnology aims at the improvement of the efficiency of crop production for biomaterials and biofuels. This includes aspects of resource-use efficiency, yield and optimisation of biomass quality for decon- struction, fermentation and gasification. The research addresses bottlenecks such as material degradation, harvest seasonality and handling/logistics of large volumes. International co-operation in non-food crops with leading third countries forms a particularly important added value in this sector. Examples include the project RENEWALL (Improving plant cell walls for use as a renewable industrial feedstock), ENERGYPOPLAR (Enhancing poplar traits for energy applications), FORBIOPLAST (Forest resource sustainabil- ity through bio-based-composite development), and 4F CROPS (Future crops for food, feed, fibre and fuel). Other examples of recent FP7-funded projects in this area include SWEETFUEL (Sweet sorghum: an alternative energy crop); COMOFARM (Contained molecular farming – controllable contained systems for high yield and consistency) and the Coordination and Support Action (CSA): CROPS2INDUSTRY (Non-food crops-to-industry schemes in EU27). Current topics include plant photosynthetic efficiency (from a C3 to a C4 system), perennial grasses (optimisation of biomass produc- tion), and an EU–India Partnering Initiative on biomass production and bio-waste conversion through biotechnological approaches. Finally, research under this area also includes activities aiming at prospecting the biological diversity for the production of commer- cially valuable compounds. Among the source organisms studied are European and non-native plant species, wild-type (including feral) plants, but the scope of the source organism is also open to include fungi and invertebrates. The research projects underway are targeted at the generation of novel lead compounds for phar- maceutical (e.g. antibacterial, antifungal) or non-pharmaceutical (e.g. chemical monomers for bio-polymer biosynthesis) use. It is expected that these initiatives will strengthen the competitiveness of the EU by providing unique classes of new drugs and other com- pounds. Two projects funded in this area in FP7 are TERPMED (Plant terpenoids for human health: a chemical and genomic approach to identify and produce bioactive compounds); and AGROCOS (From biodiversity to chemodiversity: novel plant produced compounds with agrochemical and cosmetic interest). 3. Marine and fresh water biotechnology (blue biotechnology) Blue biotechnology has a high potential for innovation that should contribute to the building of a sustainable, eco-efficient and competitive Europe. The economic and scientific potentials of aquatic environments remain under explored and their resources remain largely untapped by European industry. Marine biotech- nology has also been recognised as pivotal to shape the “Oceans for the future” and as a major element of recent calls for a strong science-based marine policy, for example in connection with the conservation and management of natural marine resources (European Commission, 2008b; European Science Foundation, 2010). The first line of marine and freshwater biotechnology research funded under FP7 aims at the exploration and industrial exploita- tion of marine biodiversity for bioactive compounds from marine and freshwater organisms. Extreme or specific environmental con- ditions (e.g. of temperature, pressure, salt content, acidity) and the enormous biodiversity of these ecosystems offer multiple opportu- nities for bio-prospecting, exploitation and use of microbes, plants and animals and of their genes and metabolic pathways. This can lead to the development of novel products for industrial appli- cations (e.g. bio-processing, bio-materials, specialty chemicals, pharmaceuticals, and aquaculture). Examples of projects include the project MAMBA (Marine metagenomics for new biotech- nological applications) aiming at the mining of enzymes and metabolic pathways from extremophilic marine organisms and of metagenomes from microbial communities; MAREX (Exploring marine resources for bioactive compounds: from discovery to sus- tainable production and industrial applications); MARINE FUNGI (Natural products from marine fungi for the treatment of cancer); SPECIAL (Sponge enzymes and cells for innovative applications) aiming at the development of anticancer drugs and novel biomed- ical/industrial applications of biosilica and collagen; and BAMMBO (Sustainable production of biologically active molecules of marine based origin) searching for solutions to overcome existing bottle- necks associated with culturing marine organisms (e.g. bacteria, fungi, sponges, microalgae, macroalgae and yeast) in order to pro- duce high yields of value-added products for the pharmaceutical, cosmetics and industrial sectors. The second line of FP7-funded research in marine biotechnol- ogy aims at optimising the potential of marine and freshwater algae to use sunlight in the production of fuels and other industrial products such as composites, chemicals, pharmaceuticals, cosmet- ics, enzymes and food additives. Examples include the project SUNBIOPATH (Towards a better sunlight to biomass conversion efficiency in microalgae) aiming at better sunlight to biomass conversion efficiency based on microalgae species, and GIAVAP (Genetic improvement of algae for value added products) aiming at genetic modification to make microalgae better suited to industrial application.
  4. 4. D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 385 The third line of marine and fresh water biotechnology research intends to broaden the range of biosensors based on aquatic organ- isms, or derived compounds, to respond to the growing demand for accurate spot and on-line measurements. The detection of tox- ins and pollutants in the environment, as well as the surveillance of production processes, are some of many examples of poten- tial biosensor applications. Projects funded under this line include RADAR (Rationally designed aquatic receptors integrated in label- free biosensor platforms for remote surveillance of toxins and pollutants) and ␮AQUA (Microarrays for the detection of pathogens and their toxins in freshwater). Finally, several projects financed under FP7 address more horizontal issues aimed at raising awareness and visibility of marine biotechnology research. Examples include MG4U (Marine genomics for users) aiming at specific dissemination research results to potential users in marine genomics. The 2011 call for proposals includes a topic within the OCEAN joint call on marine microbial biodiversity–New insights into the functioning of marine ecosystems and their biotechnological potential, also addressing the need for interdisciplinary research in coordination with the “Environment” Theme. A second topic within the 2011 call aims at fostering better coordination between the EU Member States in a marine biotechnology ERA-net preparatory action. 4. Industrial biotechnology and biorefineries (white biotechnology) Traditionally, industrial biotechnology and biorefineries are together perceived as a branch of the chemical industry focused primarily on the production of both, fine chemicals and high added value products (antibiotics, amino acids, pharmaceuticals and bio- logicals) and bulk chemicals (ethanol, biodiesel and other biofuels, bioplastics, biolubricants, etc.) from biomass. The main technolo- gies for producing these products derive from a combination of microbial fermentation, downstream processing and biocataly- sis. However, in recent years, biotechnology, and in particular, industrial biotechnology and biorefineries, are considered as Key Enabling Technologies and are emerging as the ‘engines’ of the bioeconomy, in the sense that most of the applications, products or processes from other branches of biotechnology need to pass through some form of industrial biotechnology or biorefinery pro- cess to generate the final products (European Commission, 2009). This is particularly evident in the areas of novel sources of biomass and blue biotechnology, where the terrestrial and marine derived materials need to be bioprocessed. Industrial biotechnology will enable industry to deliver novel bioproducts which cannot be pro- duced by conventional methods. It will, moreover, make possible the replacement of chemical processes by more resource-efficient biotechnological methods, with reduced environmental impact. Europe has a leading position in industrial biotechnology, in particular in the fine chemicals and enzymes markets. Industrial biotechnology represents for the European chemical industry and chemistry-using sectors, a unique opportunity for innovation and green growth in an increasingly competitive environment. Research activities in FP7 are expected to bring about the dis- covery and development of new enzymes with applications in the medical, environmental, food and chemical sectors. They will deliver enhanced microbial metabolic processes for the produc- tion of chemical and pharmaceutical intermediate products. Other important activities addressed are the development of new robust microorganisms and enzymes and the development of optimised bioprocesses. The areas of industrial biotechnology and biorefinery go hand-in-hand with the use of bioprocesses for greener products and are very much interrelated. 4.1. Industrial biotechnology The use of enzymes offers a variety of benefits as compared to conventional chemical processes. For example, it may substan- tially reduce the energy requirements and lower the production of toxic waste during the production of specialised, high value com- pounds (e.g. stereo-specific chemicals), where traditional synthesis involves many steps with toxic by-products. Thus, the first line of industrial biotechnology research supported in FP7 intends to expand the range of reactions catalysed by enzymes and improve enzyme characteristics for industrial applications. The projects, POLYMODE (Novel polysaccharide modifying enzymes to optimise the potential of hydrocolloids for food and medical applications); OXYGREEN (Effective redesign of oxidative enzymes for green chemistry); NOVOSIDES (Novel biocatalysts for the production of glycosides); and PEROXICATS (Novel and more robust fungal per- oxidases as industrial biocatalysts) investigate different classes of enzymes for various industrial applications. IRENE (In silico rational engineering of novel enzymes) adds to this portfolio addressing a challenge for the rational design of enzymes. Another challenge on the path to the production of novel bio- logical compounds on an industrial scale is metabolic pathway engineering. Therefore, another research line aims to enhance our knowledge of microbial metabolism, metabolic engineering and production systems as well as to expand the application of well-established knock-out and over-expression tools for the pro- duction of compounds of industrial relevance. Two projects in this area are being supported in FP7: LAPTOP: (Lantibiotic production: technology, optimization and improved process) and BIONEXGEN (Developing the next generation of biocatalysts for industrial chem- ical synthesis). The optimisation of multiphase and multistep bioreactors is the third mainline, under which the project AMBIOCAS (Amine syn- thesis through biocatalytic cascades) is supported. The fourth and final research line, novel and robust production micro-organisms for industrial processes, is aimed at promoting the use of novel techniques (’-omics’, synthetic, system biology and mathemati- cal modelling etc.) for practical industrial applications, such as tailor-made organisms (’cell factories’) for the production of spe- cific substances. The project SYSINBIO (Systems biology as a driver for industrial biotechnology) – a Coordination and Support Action – was funded to coordinate European activities in the field of model- driven metabolic engineering, including the establishment of a database and the coordination of education and training activities. 4.2. Biorefinery This area addresses the development and application of indus- trial biotechnologies for the conversion of renewable raw materials into sustainable and cost-efficient fine and bulk bio-products and/or bio-energy. For biofuels, the focus is on the develop- ment of second generation biofuels with improved energy and environmental balance and which avoid the potential food/fuel conflict which has challenged European society. Biorefineries can use a broad range of biomass feedstocks, ranging from ded- icated agricultural, aquatic, forest biomass chains, through to residues, by-products and wastes from biomass-based industrial sectors. The main lines of research in biorefineries are: convert- ing by-products of biomass-based industries into bioproducts; second generation biofuels; pre-treatment of lignocelluloses; con- verting biomass into chemical building blocks, and integrated biorefinery concepts, including socioeconomic and environmen- tal aspects. Some examples of FP7 projects are: NEMO (Novel high-performance enzymes and micro-organisms for conversion of lignocellulosic biomass to bioethanol) and GLOBAL-BIO-PACT (Global assessment of biomass and bioproduct impacts on socioe-
  5. 5. 386 D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 conomics and sustainability). The European Commission is also funding three large research projects with contributions from sev- eral of the FP7 Themes: SUPRABIO (Sustainable products from economic processing of biomass in highly integrated biorefineries); EUROBIOREF (European multilevel integrated biorefinery design for sustainable biomass processing) and BIOCORE (Biocommodity biorefinery). 5. Environmental biotechnology The concept of the KBBE includes environmental sustainability promoted through the development and application of mod- ern biotechnology. Research and development activities generate sustainable processes and products as well as mechanisms for preventing or cleaning-up pollution. The sector comprises the application of biotechnologies for the design, manufacture and use of more environmentally benign products and processes as well as for applications such as bio-sensors, bio-remediation, waste treat- ment and recycling. 5.1. Bioremediation Bioremediation has an enormous potential in the fight against environmental pollution resulting from household and indus- trial activities and is a key area of environmental biotechnology research. Research in this field expands current knowledge on the biodegradation of different classes of recalcitrant compounds (e.g. poly-aromatics, chlorinated compounds, heavy metals, etc.). Partic- ular emphasis is made on understanding intrinsic bio-degradation processes, involving specific genes and biochemical pathways as well as on the exploitation of the naturally occurring biocatalytic potential of organisms for cleaning-up contaminated groundwater, soil and wastewater. Efforts to promote research in bioremediation began in ear- lier Framework Programmes. In FP5 (1998–2002), the “Cell Factory” Key Action with its priority area “Improving environ- mental sustainability” enabled the funding of several projects addressing a wide range of environmental concerns and scien- tific questions in this field (Aguilar, 1999; Benediktsson, 2002). METALLOPHYTES (An integrated approach towards removal by plants of toxic metals from polluted soils); ORGANOMERCU- RIALS (Novel remediation technology for vaccine production effluents containing organomercurials); and BIOSTIMUL (Use of bioavailablility-promoting organisms to decontaminate PAH- polluted soils: preparation towards large scale field exploitation) serve as examples. ANAEROBIO-D2 (Diversity of subsoil anaerobic microorganisms and their potential for aromatic hydrocar- bons degradation) or BIOMERCURY (Worldwide remediation of mercury hazards through biotechnology) date back to FP6 (2002–2006). Collaborative projects funded under FP7 include the projects BACSIN (Bacterial abiotic cellular stress and survival improvement network); MAGICPAH (Molecular approaches and metagenomic investigations for optimizing clean-up of PAH-contaminated site); MINOTAURUS (Microorganism and enzyme immobilization: novel techniques and approaches for upgraded remediation of under- ground wastewater and soil); BIOTREAT (Biotreatment of drinking water resources polluted by pesticides, pharmaceuticals and other micropollutants); GREENLAND (Gentle remediation of trace ele- ment contaminated land) and ULIXES (Unravelling and exploiting Mediterranean sea microbial diversity and ecology for xenobi- otics’ and pollutants’ clean up). One of the main challenges for researchers in the field of bioremediation was the trans- fer of know-how from the laboratory to its application in the field. 5.2. Microbial diversity and metagenomics Metagenomics is a relatively new field in which the power of genomic analysis (the analysis of all the genetic material of an organism) is applied to entire communities of microorganisms (bacteria, fungi, yeasts) bypassing the need to isolate or culture them. This powerful technique enables mining of enormously rich genetic resources and, thus, not only increases our knowledge on the functioning of microbial communities but also substantially stimulates progress in biotechnology. Metagenomics has changed the pace in which new genes, pathways and enzymes are being discovered and its tremendous impact may be observed in the development of new bio-based products (commodities, chemicals, pharmaceuticals) and processes (bioremediation, bio-synthesis, etc.). One of the first European consortia working on metagenomics was the FP6-funded project METAFUNCTIONS (Environment and meta-genomics – a bioinformatic system to detect and assign functions to habitat specific gene patterns). In FP7, metagenomics is approached more thoroughly and forms an important line in environmental biotechnology. Thus far, two specific calls on metagenomics were published, in which the projects METAEX- PLORE (Metagenomics for bioexploration – tools and application) and HOTZYME (Systematic screening for novel hydrolases from hot environments) have been funded. In recent years, progress in metagenomics techniques has allowed the scientific commu- nity to focus on and apply metagenomics as a tool for developing new products and processes in the areas of marine and industrial biotechnology. The progress in metagenomics is being accompanied with the development of bioinformatics as the huge amount of data gen- erated by novel sequencing techniques (e.g. shotgun sequencing, pyrosequencing etc.) require powerful tools for analysis. The future trend should be the integration of these two disciplines and the development of informatics systems that correspond directly to the needs of different biotechnology domains (bioremediation, eco- efficient processes, synthetic biology etc.). 5.3. Development of biotechnology-based eco-efficient processes Exploiting and integrating advances in modern biotechnologies allow more efficient and safer production processes, in particular through the substitution of harmful substances. Research in this domain focuses on the design, manufacture and use of environmen- tally benign chemical products and processes that reduce pressure on our natural resources, improve the quality of the life of European citizens, and stimulate economic growth. Projects such as EPOX (Engineering integrated biocatalysts for the production of chiral epoxides and other pharmaceutical inter- mediates) date back to FP5. In FP6 this research line was continued with projects such as BIOMINE (Biotechnology for metal bearing materials in Europe) and SOPHIED (Novel sustainable bioprocess for European color industries). One project, ANIMPOL (Biotechno- logical conversion of carbon containing wastes for eco-efficient production of high added value products) has been supported in FP7. Biotechnology also offers a unique opportunity to valorise the continuously increasing amount of biowastes originating from agri- cultural, industrial and municipal residues, and helps convert them into valuable products with different applications. Thus, in FP7, the Biotechnology activity has continuously supported research aimed at turning organic litter and by-products into bioresources. For example, PROSPARE (Progress in saving proteins and recov- ering energy) addresses novel methods for processing animal by-products for producing substances with valuable functional properties. FORESTSPECS (Wood bark and peat based bioactive
  6. 6. D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 387 compounds, speciality chemicals, and remediation materials: from innovations to applications) focuses on the manufacture of value- added chemicals and materials using by-products from the forestry industry. As a result of scale of the problem and its relevance not only to the industrialised countries but also to the developing world, biowaste remains a focus for the latest FP7-KBBE calls. A topic addressing the development of novel biotechnological approaches for transforming industrial and/or municipal biowaste into bioproducts, where a substantial participation of International Cooperation Partner Countries partners is requested, has been pub- lished in 2011. In the same call, an EU-India partnership initiative on biomass production and bio-waste conversion through biotech- nological approaches has also been launched. Finally, in 2012, the Commission intends to propose a topic on biowaste conversion in developing countries, with particular relevance to African and Mediterranean Partner Countries. For many years, combating environmental pollution through bioremediation was the main focus of environmental biotechnol- ogy. Advances in metagenomics and bioinformatics changed this perspective as the link between studies on microbial communities and the development of new bio-based products (commodi- ties, chemicals, pharmaceuticals) and processes (bioremediation, bio-synthesis etc.) became apparent. The achievements of envi- ronmental biotechnology began to serve not only the environment but also industry. Thus, much of the future potential of the field is probably through interactions and synergy with industrial biotech- nology/biorefineries, devising and developing technologies aimed at preventing pollution and improving resource efficiencies. The ultimate goal is to “green the chemical industry” by the grad- ual replacement of raw materials coming from fossil fuels with renewable bio-based materials, and by replacing conventional chemical processes by biotechnological ones. To this end, the alliance between industrial biotechnology/biorefineries and envi- ronmental biotechnology will help develop a lead market on new bio-based products (European Commission, 2007) and at the same time constitute a measurable contribution to reducing energy con- sumption and greenhouse gas emissions (World Wildlife Fund, 2009). 5.4. Genetically modified organisms (GMOs) Since its inception in 1982 in the First Programme in Biotech- nology, the Biomolecular Engineering programme, the European Commission has invested more than D 300 million in research projects examining the biosafety, environmental and health effects of genetically modified organisms (GMO). A first overview of the results achieved was published in 2001 in a book “EC Sponsored Research on Safety of Genetically Modified Organisms” (Kessler and Economidis, 2001). This publication fea- tured 81 projects, involving over 400 laboratories, and the results covered a range of subjects: horizontal gene transfer, environ- mental impacts of transgenic plants, plant-microbe interactions, transgenic fish, recombinant vaccines, food safety, and other issues. A decade later, the European Commission published “A decade of EU-funded GMO research” (European Commission, 2010a), presenting the outcomes and conclusions of research projects sup- ported in the period 2001–2010. The 50 research projects presented in the book, accounting for some D 200 million of European Union support, are grouped into the four principal areas: environmental impact of GMOs (21 projects); GMO and food safety (10 projects); use of GMOs for biomaterials and biofuels; emerging technologies (9 projects); and risk assessment and management; support and communication (10 projects). It is evident from this grouping that many of the research projects have been launched to address not only the scientific unknowns but, also to provide the scientific and factual evidence to address public concerns about the potential environmental impact of GMOs, the safety of GM foods, the co-existence of GM and non- GM crops, and risk assessment strategies in Europe. The results and conclusions of these projects increase our cumulated knowledge, enabling the European Commission and policymakers in general to contribute to the international debate, and to provide scien- tific support to regulatory frameworks and initiatives. Besides the individual project reports, each project has produced numerous peer-reviewed scientific publications, underpinning the quality of the research undertaken and providing scientific evidence for car- rying out risk assessment and risk management. Some of the research projects, primarily aiming at identify- ing environmental effects of GMOs, revealed that experiments with various BT-toxins did not show major adverse effects on the overall arthropod (non-target organisms) biodiversity (BT- BIONOTA: Effects and mechanisms of Bt transgenes on biodiversity of non-target insects: pollinators, herbivores and their natural enemies). No significant impacts of GM-potatoes on indigenous soil microbiota were found (POTATOCONTROL: Impact of three selected biotechnological strategies for potato pathogen control on the indigenous soil microbiota), while another project (ECOGEN: Soil ecological and economic evaluation of genetically modified crops) concluded on the basis of their experiments that changes in soil microbiota where due to changes in farming practices rather than effects of BT-toxins from GM plants. The possibility of gene transfer between GM plants and soil bacteria or viruses was found to be unlikely (BIOT-CT91-0282: Analysis of gene transfer between micro-organisms and plants), and the uptake of GM plant transgenes by gut-dwelling eukaryotes of ruminants could not be detected in experiments lasting for 2–3 years, (CIMES: Ciliates as monitors for environmental safety of GMO). In addition to examining the environmental impact of GMOs as such, key aspects of crop improvement have also been tar- geted, such as developing plants with resistance to fungi or plant parasitic nematode pathogens, constituting major sources of har- vest losses and/or reduced product quality of agricultural crops in Europe. These projects, EURICE (European rice transgenes for crop protection against fungal diseases) and NONEMA (Making plants resistant to plant parasitic nematodes: no access–no feeding) were not only successful in that they provided viable biotechnological solutions for these problems, but also demonstrated alternatives for reducing the environmental footprint of agriculture as a result of the more specific and targeted response mechanisms developed and the possibility for reducing pesticide application. The projects SUSTAIN (Developing wheat with enhanced nitrogen use effi- ciency towards a sustainable system of production) and ECOSAFE (Biosafety research directed at more sustainable food production) developed new insights and alternative approaches to the excessive and environmentally damaging use of chemical fertilisers. The environmental effects of GMOs continue to be one impor- tant priority in FP7. However, given that GMOs so far have not been proven to be more environmentally harmful than conven- tional crops, future research needs to include the potential benefits of GMOs as compared to baseline conditions (e.g. conventional agri- culture and organic farming). 6. Emerging trends in biotechnology Novel technologies and new trends in biotechnology will be instrumental for the rational advancement of the bioeconomy. The potential of metagenomics, bioinformatics, systems biology, vir- tual cells, synthetic biology and nano-biotechnology is becoming ever more apparent. These and related fields deserve appropriate measures in terms of research and development so as to facili-
  7. 7. 388 D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 tate effective implementation into industrial and biotechnological applications. Among the different emerging trends, synthetic biol- ogy may have the most potential to influence, or even transform, our economy and society. 6.1. Nano-biotechnologies Nano-biotechnology is mainly based on the convergence between nanotechnology products with the basic components of biomolecules and living cells. The interface of both fields has the potential to provide innovative scientific and technical approaches to address existing or new applications. Principles, tools, and processes of nanotechnology are applied to the life- sciences in order to develop new products and processes, such as nano-biosensors, membranes/filters, nano-proteomics, nano- fluids, biomolecular interactions. “Nanoscience and nanotechnology, new materials and new pro- duction processes and devices” thematic area under FP6 (NMP) prepared the ground for research on nano-biotechnologies. Projects like NANO2LIFE (A network for bringing nanotechnologies to life) facilitated networking to bring nanotechnologists closer to biologists. Other relevant projects were FRONTIERS dealing with nanotechnology research and facilities targeted at life science and NABIS (Nanobiotechnology with self-organising structures). In FP7 the KBBE programme undertook activities on nano-biotechnology based biosensors (NANOBE: Nano- and microtechnology-based analytical devices for online measure- ments of bioprocesses) and other relevant activities co-funded and implemented with the FP7 Theme “Nanosciences, nanotechnolo- gies, materials and new production technologies”. Examples are smart nano-biotechnology devices to study biomolecule dynamics in real time (DINAMO: Development of diamond intracellular nanoprobes for oncogen transformation dynamics monitoring in living cells), Nano-biotechnology for functionalised membranes (MEM-S: Bottom-up design and fabrication of industrial bio- inorganic nano-porous membranes with novel functionalities based on principles of protein self-assembly and biomineraliza- tion), and nano-biotechnology for bio-interfaces for environmental applications (BIOMONAR: Biosensor nanoarrays for environmental monitoring). 6.2. Bioinformatics Bioinformatics has been developed and used in the life science and biotechnologies in multiple ways and for diverse applications. The objective is to develop innovative approaches and tools to transform available information into biotechnologically applica- ble knowledge. Modern biotechnology research and applications require an increased data handling capacity – typical examples are the screening of environmental metagenomes and models in systems biology. In FP6 different European programmes invested in different areas of bioinformatics. Examples are drawn from programmes such as “Infrastructures” (BIOINFOGRID: Bioinformatics grid appli- cation of life science), “Life Sciences, and Applied Genomics and Biotechnology for Health” (EMBRACE: European model for bioinformatics research and community education), and “Infor- mation Society Technologies” (BIOSAPIENS: integrated genome annotation). The latter is a “Network of Excellence” involv- ing 25 institutions from 14 countries. In FP7 the Theme KBBE currently finances a project on microbial genomics and bioinfor- matics (MICROME: A knowledge-based bioinformatics framework for microbial pathway genomics). However, more projects are expected to be funded following the 2011 call for proposals covering topics from the increasing bioinformatics capacity for biotechnological applications to marine metagenomics. 6.3. Synthetic biology This is a new and rapidly developing discipline that aims at the (re-)design and construction of biological systems. The arti- ficial reduction of the microbial genome will identify the minimal genomic building blocks needed for life. A minimal cell will be a considerably simpler living system, more amenable to integrated experimental and theoretical approaches. Systems level under- standing of a minimal cell will enable predictable engineering for biotechnological exploitation. Using technologies to develop engi- neered biological systems through the design and construction of artificial micro-organisms for a given application has enormous potential for biotechnological applications. Several of these can be envisioned in the fields of protein design and production, metabolic engineering, carbon fixation, biomass production, biocatalysis, bio- fuels and bioremediation. In FP6 the Community programme NEST (New and Emerging Science and Technologies, 2002–2006) mobilised the European sci- entific community and prepared the ground for several research projects in the domain of synthetic biology. In FP7 the Theme KBBE considered synthetic biology one of its emerging technologies for future trends in the biotechnologies. In this spirit it started with a coordination action investigating the possibility of applying syn- thetic biology methods for attacking pollution (TARPOL: Targeting environmental pollution with engineered microbial systems à la carte). In addition the issue of minimal genomes in biotechnological applications was approached by the project BASYNTECH (Bacterial synthetic minimal genomes for biotechnology). In 2011 several projects are expected to be financed on topics varying from to the application of the technology in the notion of ‘cell factory’. All projects will take into consideration the recom- mendations expressed by the Opinion of the European Group of Ethics in Science and New Technologies to the European Commis- sion (EGE) on the “Ethics of synthetic biology” (2009). In addition, research studies on issues of governance, risks, ethics and other aspects of legal and socioeconomic nature will be initiated in col- laboration with the FP7 Theme on “Socio-economic sciences and humanities”. 6.4. Systems biology Rather than operate at the level of component parts, systems biology aims to understand the operation of a system as a whole. However, most of the techniques are still far from routine appli- cation. Systems biology has attracted considerable attention in different organisms and from different disciplines. The combina- tion of systems biology and engineering offers interesting potential for industrial applications. Virtual or in silico models could reduce the need to carry out experiments. The successful application of such methods could lead to decreased development costs and reduced development times for new products and processes. In FP6 most of the activities of systems biology were sup- ported by the Theme of “Life Sciences for Health”, including the projects: EUSYSBIO (The take-off of European systems biology); STREPTOMICS (Systems biology strategies and metabolome engi- neering for the enhanced production of recombinant proteins in Streptomyces); YSBN (Yeast systems biology network) and DIA- MONDS (Dedicated integration and modelling of novel data and prior knowledge to enable systems biology). In FP7 under the KBBE Theme approaches of systems biology can be found in projects such as BACSIN (see 5. Environmental biotechnology) and MICROME (see Section 6.2). However, major efforts and investments are
  8. 8. D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 389 still needed to fully incorporate systems biology into (non-health) biotechnology. 7. International cooperation in biotechnologies The strategy for international co-operation in the area of biotechnologies addresses specific challenges that third countries face or that have a global character on the basis of mutual interest and benefit, taking into account EU policies and inter-governmental dialogues, and considering the reflections of ad hoc international platforms and working groups. The EC Communication “A Strate- gic European Framework for International Science and Technology Co-operation” (European Commission, 2008a) is the main reference for international co-operation in FP7. It defines the core principles and orientations for actions: to put the European Research Area on the global map and contribute to global sustainable develop- ment by enhanced international partnerships. These approaches focus on a strong interaction with Member States’ research pro- grammes. With the aim of increasing the scale of activities, the strategy is promoting cooperation at programme level with the strong involvement of researchers and the full coverage of research areas in biotechnologies. A focus on clearly identified strategic partners gives strength and reduces duplication of cooperation activities. Various tools for international co-operation have been pro- moted in FP7, including the general opening of all activities and topics to third country partners. There is also targeted opening to encourage the participation of non associated third countries and, finally, there are Specific International Co-operation Actions (SICAs) which require the compulsory participation of some inter- national cooperation partner countries, on the basis of shared interest and mutual benefits. Other collaborative approaches include the twinning of projects between FP7 and those from third countries (such as Canada and Argentina), and a ‘part- nering initiative’ consisting of co-ordination actions carried out by the European Commission jointly with interested Member States and individual major third country partners (such as China and India) with the aim of systematically linking research programmes. Implementation of international scientific cooperation lies also with a series of Science and Technology Bilateral Co-operation Agreements that the EC has signed with 19 countries (Argentina, Australia, Brazil, Canada, Chile, China, Egypt, India, Japan, Jordan, Korea, Mexico, Morocco, New Zealand, Russia, South Africa, Tunisia, Ukraine and United States of America). 7.1. USA The main tool to frame the Europe-USA cooperation is the EU- US Taskforce on Biotechnology Research, set up in 1990 by the European Commission and the White House Office of Science and Technology. It acts as an effective forum for discussing, coordi- nating and developing new ideas on the future of biotechnology with the participation of the Directorate General for Research and Innovation and US Federal funding agencies (NIH, NSF, DOE, USDA, etc.). In the frame of the taskforce, several workshops and summer schools have provided information, debate and analysis for estab- lishing emerging scientific fields on biotechnologies including, for example, animal and plant bioinformatics, standards in synthetic biology, marine genomics and biotechnology for sustainable bioen- ergy. Currently, the taskforce’s activities are mainly implemented in five working groups: animal biotechnologies; biobased products and bioenergy; marine genomics; environmental biotechnology; obesity and synthetic biology. 7.2. Russia The EU-Russia Working Group on Agro-Bio-Food with the Rus- sian Federal Agency for Science and Innovations set up in 2005 provides an annual forum for the planning of activities in areas of shared interest. In the frame of these activities, a coordinated call has been successfully implemented with Russia in 2007. Two coor- dinated projects have been funded in the area of the design and production of industrial enzymes (DISCO: Targeted discovery of novel cellulases and hemicellulases and their reaction mechanisms for hydrolysis of lignocellulosic biomass) and in plant-produced vaccines (PLAPROVA: Plant production of vaccines). 7.3. Canada The EU-Canada Working Group on agro-bio-food with Agricul- ture and Agri-Food Canada (AAFC) was established in 2007. Under its umbrella joint activities are implemented such as workshops and the twinning of projects. Since 2007 Canadian and Euro- pean projects exchange information and data, organise short term scientific visits, and organise events in the area of biomass, bioma- terials and biorefineries. In 2010 this WG was extended to include Australia, Canada and New Zealand in the frame of the ‘KBBE Forum’ where four main areas of common interest were identified: sus- tainable agriculture, bio-products and bio-materials, fisheries, and food. The first Canada–Europe–Australia–New Zealand Workshop on biotechnologies for biorefinery and biobased materials was held in Saskatoon (Canada) in October 2010. 7.4. India A long standing focus on India aims to better coordinate research efforts undertaken to address global challenges. A working group has been established with the Department of Biotechnology of India’s Ministry of Science and Technology aiming at identifying possible synergies and to bring together European and Indian sci- entists. In the frame of this cooperation the organisation of events such as the Delhi conference on “India-EU and Member States Partnership for a Strategic Roadmap in Research and Innovation” (European Commission, 2010c) and common research activities as the partnering initiatives on biomass and biowastes published in the Work Programme 2011 (European Commission, 2010d) have been supported. 7.5. China Long-standing strategic activities with China have been devel- oped since 2002. Recently, there has been a more strategic approach, broadening the policy dialogue in the KBBE and explor- ing options for cooperation in biotechnology, specifically with the Chinese Academy of Agricultural Sciences (CAAS). Examples of this successful cooperation are common initiatives in the area of plant breeding and biotechnology where partnering initiatives such as the project OPTICHINA have been funded (European Commission, 2010d). 7.6. Argentina and MERCOSUR Within MERCOSUR, and in particular with Argentina, EU and local projects have been linked through twinning in the areas of soils, plants and food research. This cooperation envisages devel- oping summer schools, joint publications and the exchange of scientists. To date, 39 groups from third countries have participated in FP7-funded biotechnology projects. Russia, US, Canada, Brazil and South Africa have contributed the majority of these groups.
  9. 9. 390 D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 Table 1 Average number of partners and private sector participation in different types of projects funded in FP7-KBBE calls (2007–2010) under Activity 2.3 “Life sciences, biotechnology and biochemistry for sustainable non-food products and processes”.a EU contribution (MD ) Number of projects funded in FP7 Average number of participants SME participation in EC contribution (%) Industry/enterprise participation in EC contribution (%) Total private sector participation in EC contribution (%) Large collaborative projects (CP-IP) Up to 6 or 9 16 14 14.89 2.99 17.88 Small/medium size collaborative projects (CP-FP) Up to 3 33 10 12.57 4.90 17.47 Specific International Co-operation Actions (SICA) Up to 3 9 8 10.69 8.63 19.32 Coordination and support actions (CSA) Up to 1 3 8 19.65 2.91 22.56 Total 262.84 61 12 13.77 4.22 17.99 a The data is not final as some of the contracts have not been concluded yet and there are constant changes in the project consortia due to addition and withdrawal of the partners. More than 50% of the third country partners are involved in projects in the area “Novel sources of biomass and bioprod- ucts”. Overall, of 730 partners involved in FP7 biotechnology projects, 7% are from Associated Countries, 3% from industrial- ized Countries and 11% from International Cooperation Partner Countries. 8. Summary and outlook To date, FP7 has supported over 730 partners in 61 projects, with a total budgetary commitment of over D 260 million in the fields of biotechnology for non-medical applications. While most partners in the projects are public research organi- sations and universities, private sector partners account for 25% of all beneficiaries (over 180 partners, Fig. 3). Overall, there is strong interest from industry (large companies and SME) in the “Biotechnologies” activities in FP7 and, con- comitantly, significant financial support to private organisations, reflecting the innovative potential of the biotechnology sector. Interestingly, while it is often assumed that the important SME sector finds smaller research projects easier to participate in, it appears that larger cooperation projects contribute slightly more to SME partners than do small cooperation projects (14.9% of total funding compared for larger projects compared to 12.6% for smaller ones Table 1). Efforts are underway to increase SME participation in projects, and this increase is reflected in the latest call for which figures are available (Fig. 4). Fig. 3. Participation of 61 projects funded in five FP7-KBBE calls (2007–2010) under Activity 2.3 “Life sciences, biotechnology and biochemistry for sustainable non-food products and processes”. (The data is not final as some of the contracts have not been concluded yet and there are constant changes in the project consortia due to addition and withdrawal of the partners.) One reason for the relevance of this research sector to industry is undoubtedly the importance of the European Technology Platforms (ETP), set up initially under the previous Framework Programme, FP6, with the aim of developing a common vision, and achieving that vision by means of a strategic research agenda, in a number of fields (Cordis, 2011b). Several are of direct relevance to biotech- nologies including, among others, the Sustainable Chemistry ETP (SusChem, 2011) and the Plants for the Future ETP (2011). The strategic research agendas of these platforms are one input into the development of the annual work-programmes, reflecting their importance to European research. In addition, the field is supported by a range of European Research Area networks (ERA-nets), which bring together differ- ent funding programmes across Europe, and in some cases beyond Europe, with a view to developing common funding programmes between Member States. ERA-nets support research in a number of biotechnology fields, including systems biology, bioenergy and industrial biotechnology, and are expected to be developed for syn- thetic and marine biotechnology too. In the final three FP7-KBBE calls (2011–2013) even more empha- sise is being given to bringing together research and innovation to address major challenges. The work programmes have been designed to support the implementation of the Innovation Union initiative (European Commission, 2010e). More topics aimed at generating knowledge to deliver new and more innovative prod- ucts, processes and services will be launched including pilot, demonstration and validation activities. The focus on innovation Fig. 4. Private sector (SME and industries/enterprises) participation (%) in the EC contribution of the projects funded in five FP7-KBBE calls (2007-2010) under Activity 2.3 “Life sciences, biotechnology and biochemistry for sustainable non-food prod- ucts and processes”. (The data is not final as some of the contracts have not been concluded yet and there are constant changes in the project consortia due to addition and withdrawal of the partners.)
  10. 10. D. Cichocka et al. / Journal of Biotechnology 156 (2011) 382–391 391 will be reflected in the description of the objectives and scope of the specific topics, as well as in the expected impact of the research. Applicants will be invited to identify and to fully address exploitation issues, such as dissemination and enhanced use of the knowledge generated. Biotechnology within the European Framework Programmes for research represents a set of active and developing technolo- gies. A majority of European citizens, 53% in a 2010 Eurobarometer survey, are optimistic about biotechnology despite reservations about some of the aspects involved, such as genetic modifica- tion for food (Gaskell et al., 2010). European research continues to seek to exploit the potential of the biotechnologies for Euro- pean society and to understand and address citizens’ concerns where they occur. 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