Contract Agreement: 691095 Website: http://www.ubu.es/iccram Coordinator: Universidad de Burgos-ICCRAM (Dr. Santiago Cuesta-López)
Table 1 Consortium List.
No. Beneficiary name Short name Country
1 UNIVERSIDAD DE BURGOS UBU Spain
2 UNIVERSITA DEGLI STUDI DEL PIEMONTE ORIENTALE AMEDEO AVOGADRO UPO Italy
3 THE UNIVERSITY OF BIRMINGHAM UoB United Kingdom
4 BIONANONET FORSCHUNGSGESELLSCHAFT MBH BNN Austria
5 Research and Development of Carbon Nanotubes S.A. NTHINX Greece
6 SITEX 45 SRL S45 Romania
7 NOVAMECHANICS LIMITED NovaM Cyprus
8 NANOTECHNOLOGY INDUSTRIES ASSOCIATION AISBL NIA Belgium
Contents
1 Summary ...72 2 Background ... 73 3 Scientific and technological challenges ... 73 4 Objectives ... 73 5 Organisation ... 74
6 Progress and Outcomes to date ... 75 7 Expected Impact ... 75 8 Directory ... 76 9 Copyright ... 76
1 Summary
Project Duration: 48 Project Funding: 706.500€
NanoMaterials (NMs) safety is of great societal concern and raises many questions for the general public, governments, industry, scientists and regulators. Identifying and controlling the hazards associated with NMs is required to ensure the safety in parallel to exploiting the technological benefits. NANOGENTOOLS answers this challenge by creating a collaborative excellence-based knowledge exchange network that will: i) push forward knowledge via method development and pre-validation, ii) train scientists in new methodologies to assess long term nanosafety, and iii) support their inclusion in standardization and EU regulations. NANOGENTOOLS combines toxicogenomics, proteomics, biophysics, molecular modeling, chemistry, bio/chemoinformatics to develop fast in vitro high through put (HTS) assays, with molecular based computational models for nanotoxicity. Its objectives are to:· Provide solutions for faster, more reliable assessment of NM toxicity and propose HTS and
omics tools for predicting toxicological properties of NMs.·
Develop new bioinformatics methodologies for analyzing -omics data and create an open database in collaboration with the EU Nanosafety Cluster.· Conduct research and training on biophysical techniques and mathematical models for accurate and fast nanotoxicity prediction.· Build/improve the safe by design concept, demonstrated using carbon-NMs and nanosensors.· Place our new knowledge in the context of regulations and EU roadmaps.
NANOGENTOOLS brings together cutting edge research, innovative knowledge-transfer and codevelopment, and cross-sectoral and cross-disciplinary secondments linking EU academic institutes/networks with industry and policy makers across 8 countries.
2 Background
Nanotechnology will be one of the key technological drivers in building an innovation European Union (EU) based on smart, sustainable and inclusive growth, and has been identified as a key-enabling technology (KET) for the EU.
The value of Nanotechnology relies in its potential to bring new materials with new or enhanced physico- chemical properties for industrial applications that are different from their micron-sized counterparts. As a result, the engineered nanomaterials (NMs) market is growing rapidly worldwide, and fostering the development of new consumer products that greatly impact almost every industrial and manufacturing sector worldwide. In the last decade, advances in NMs and nanotechnology have impacted the cosmetics, food and packaging industries and more recently biomedical applications, such as drug delivery, gene therapy or medical imaging have emerged.
By the end of 2015, the Nanotechnology World Market Size was predicted to hit €3trillion across a broad range of sectors (chemical manufacturing, pharmaceuticals, aerospace, electronics, materials etc.)[1-2], while by 2025, nanotechnology is expected to be a mature yet still growing industry, with countless mainstream products in all industrial sectors. In this context, Europe aims to play a market leader position, increasing its competitiveness in all sectors where nanotechnology may have a strong added value.
However, growth and commercialization of nanotechnology must be guided and fostered by responsible innovation taking account of social and sustainability aspects.
Without doubt one of the most difficult challenges faced in the exploitation of nanotechnology for the benefit of European society (and beyond) has been the uncertainty surrounding the potential associated risks. Moreover, as in all industrial applications, the potential exposure of humans and the environment to these materials is inevitable. As these new materials go through their life-cycle – from development, to manufacture, to consumer usage, to final disposal – different human groups (workers, bystanders, users), environmental compartments (air, soil, sediment, water), and species (e.g. worm, fish or human through secondary exposure) will be exposed to them. Consequently, NM safety is of great societal concern and raises many questions for the general public, governments, industry, scientists and regulators.
Identifying and controlling the hazards associated with NMs is required to ensure the safety of the general public, workers and the environment in parallel to exploiting the technological benefits associated with nanotechnologies.
While current data available on environmental and human toxicity of numerous NMs is starting to reach satisfactory levels, the time taken to produce safety dossiers is high and joint efforts between research scientists from academia and industry are needed to enhance the pace and reduce the cost of assessing the safety of NMs and nano-enabled products, to cope with the vertiginous growth of NMs expected for the next decade.
To meet this challenge, toxicological testing methods suitable for the detection of different/specific health effects are needed urgently, in addition to identification and/or development of suitable (new) toxicological models (in vivo & in vitro), and fast screening options for investigation of toxicity during the product development phase.
3 Scientific and technological challenges
NANOGENTOOLS answers this challenge by fostering a timely key action joining industry and academia to create a collaborative excellence-based knowledge exchange network pushing forward and training scientists in new methodologies to assess long term nanosafety, testing their applicability for NMs and pre-validating them, and finally discussing their relevance and suitability for standardization and inclusion in present and future EU regulations.
NANOGENTOOLS will answer this need and request, by combining genomics (toxicogenomics), proteomics and multidisciplinary science (biophysics, molecular modeling, chemistry, bioinformatics, chemoinformatics) to develop fast in vitro high throughput (HTS) assays, combined with molecular based computational models that will lead to better understanding of the molecular fundamentals behind nanotoxicity, and plant the seed for development of long term valuable predictive nanosafety tools for industry, including online assays during product development.
4 Objectives
NANOGENTOOLS pursues the main objective of generating a common solid knowledge basis arising from the Associated with fruitful cross-sectorial synergy between forefront research centers in nanosafety and industry, in a cross-fertilization multidisciplinary approach that will provide new tests and methodologies (or improve existing ones) to assess the long term risks of nanomaterials (NMs) in a rapid and cost effective manner suitable for regulatory inclusion. Its objectives are to:
· Provide solutions for faster, more reliable assessment of NM toxicity and propose HTS and omics tools for predicting toxicological properties of NMs.
· Develop new bioinformatics methodologies for analyzing -omics data and create an open database in collaboration with the EU Nanosafety Cluster.
· Conduct research and training on biophysical techniques and mathematical models for accurate and fast nanotoxicity prediction.
·Build/improve the safe by design concept, demonstrated using carbon-NMs and nanosensors.
· Place our new knowledge in the context of regulations and EU roadmaps.
The objectives converge to the main concept of NANOGENTOOLS, summarized in Figure 1.
Figure 1 : NANOGENTOOLS will provide technical skills to the individuals involved in the project, of relevant value for their career development and aligned with the present EU nanotechnology labour market needs.
5 Organisation
The MSCA-RISE (Research and Innovation Staff Exchange) project, NANOGENTOOLS, will ensure the delivery and alignment of key functionalities, which will allow exploitation of the exchange services in order to answer key questions important to both academic researchers and firm interests in the field of nanotoxicity and in the production of safe by design nanomaterials.
NANOGENTOOLS will focus on the following innovation activities &
research methodologies:
The first action targeted by NANOGENTOOLS will foster research on new methodologies and tests based on -omics approaches.
A new approach to understand the molecular mechanisms of toxicity induced by NMs and its Mode of Action is toxicogenomics.
This approach provides knowledge of the complex interaction between the structure and activity of the genome and adverse biological effects caused by exogenous agents such as NMs. The genomic approach provides information about specific mechanisms at the molecular level (e.g. oxidative stress);
toxicogenomics has proved to be a powerful tool for the direct monitoring of patterns of cellular perturbations in specific pathways, through identification and quantification of global shifts in gene expression resulting within treated cells [5].
Gene expression profiles by RNA-sequencing is the first molecular apparatus that NANOGENTOOLS plans to use and validate with carbon-NMs as a HTS tool for long term prediction of their associated risks. Quantitative RNA-sequencing by Illumina Hi-Seq will provide the required profundity to identify robust gene changes. A typical experimental design for RNASeq will encompass 20 million 100 bp paired-end sequence reads for each analyzed condition with biological triplication (60M PE sequences per condition). Such analyses will provide the applicability and ability of QSAR models for read-across within & across NM families.
The second action on which NANOGENTOOLS will focus is the development and adaptation of a new collection of approaches
based on multidisciplinary science and biophysics, as a new tool to complement the -omics methods in an effort to provide efficient fast assessment of nano safety to industry. This activity will facilitate the combination of biophysical methods (Microscopy, Raman spectroscopy, AFM, DSC, ITC, molecular and elemental imaging) with -omics to enhance understanding of NMs toxicity mechanisms and identify novel predictive endpoints based on elemental/molecular signatures of induced toxicological processes.
The third line of action carried out within NANOGENTOOLS will be development of better understanding of the concept of 'safe by design' (WP4). As a conclusion of the research and learning activity, the safe-by-design concept will be applied to the construction of a nanosensor based on a carbon-NM. The whole know-how and data arising from WP2 and WP3, applied to carbon-NMs converge to improve the safe-by-design approach and support a safe design of a nanosensor (WP4).
Finally, NANOGENTOOLS, will conduct research into understanding the recent policy efforts and regulation mechanisms, as well as the priority roadmap for nano safety research 2015-2025 set up by the Nanosafety cluster and the EU Commission(WP5). According to such priority roadmaps, there is a clear urgency to regulate occupational and environmental exposure to NMs, as well as to develop new fast screening methods for the risk and heath issues prediction of engineered NMs, paying attention to: suitability for implementation in industry (particularly SMEs); cost reduction; and reduced use of animals, thus putting emphasis on in vitro or modeling methodologies.
Figure 2. NANOGENTOOLS RISE action work package structure. The overall work package structure of NANOGENTOOLS RISE action and their dependencies. Interactions between WPS and activities as well as the multidisciplinary aspect are depicted here.
The following approach and methodology for knowledge sharing will be used: NANOGENTOOLS will use a two-fold approach for ensuring a clear and efficient sharing of knowledge across the partnership.
1. Dedicated trans-national and trans-sectoral multidisciplinary secondments designed to have a high degree of complementarity and sharing of knowledge and ideas from research to market (and vice-versa). With respect to the training activities, early stage
researchers will be advised throughout all their secondment periods by host-organization staff (see Figure 3). Joint on-line meetings will also be organized, to ensure continuity between the ESRs in secondments and the senior staff.
Figure 3: NANOGENTOOLS network of eligible secondments
2. Dedicated training, learning and dissemination activities to enhance the continuous knowledge flow between Academia experts in different techniques to predict materials nanosecurity and enterprises related to nanotechnology working on the concept of “Safe by Design” and interested in developing know-how about new technologies that ensure long-term absence of the hazards of nanotech based products.
6 Progress and Outcomes to date
The main progress up to now is summarised below, related to the project milestones:
MS1 progress:
A collection of methods has been set for genotoxicity and safety assessment of nanomaterials. Efficient exchange of this knowledge has been started through secondments, and analysis of carbon based nanomaterials (CNTs and graphene family products) started.
MS2 progress:
Several Biophysically based techniques have been set up in UBU-ICCRAM (i.e. AFM of NPs+cells, AFM-RAMAN, RAMAN). Preliminary validation tests are being performed in TiO2 NPs and monolayer graphene oxide. Methods and knowledge are ready to be transferred through hosted secondments during 2017 and 2018.
MS4 progress:
Safe by Design (SbD) methodology has been trained through different secondments and consortium discussions. A preliminary prototype for a SbD product based on nanoelectronics and graphene-based inks has been drafted. Work to progress in this line is specifically planned through secondments in 2017 and 2018.
Consortium is improving and setting up new updates within the ENALOS platform (secondments at NovaM)
An international industrial workshop on SbD concept merging results of different EU projects dealing with nanosafety and the SbD concept has been designed and organized, and was hold in Bilbao on April 2017, helping to develop new relationships between the H2020 projects in SbD and industrial stakeholders
MS5 progress:
Preliminary discussions on regulation and standardization have started. This topic was part of the industrial workshop organized in Bilbao on April 2017.
Also a Nanotechnol0gy Round table was organized in Brussels on May 2017 with the objective of discussing current thinking and regional interest in nanotechnologies and examining specific areas of interest such as nano-safety
MS6 progress:
Activities within the workshop organized (SAFE BY DESIGN INDUSTRIAL WORKSHOP - safety critical issues and their impact on EU society and industry-) had as target industrial dissemination and communication.
Moreover, a specific campaign of visiting nanotechnology based companies to review their products under the SbD concept was carried out during 2017.
MS7 progress:
A communication and dissemination plan has been designed and implemented. Project web site was designed, open made public and it is periodically updated.
Several communications activities and measures have already been done. Project objectives has been communicated to the EU Nanosafety cluster, and a couple of publications in newsletters delivered (EU-Nanosafety Cluster e-newsletter (03/2016 and 07/2016 - Compendium)).
Specific training targeting new generation of researchers is scheduled and planned for Autumn 2017, through the EU NANOGENTOOLS AUTUMN SCHOOL “Advanced Training in understanding the Safety of Nanomaterials”.The event will be held three days between 27th-29th of September 2017 at the University of Burgos facilities in Burgos, awaking the curiosity of young researchers in the related subject.
7 Expected Impact
NANOGENETOOLS will contribute to foster regulation, discuss standards and validate new fast tests suitable to be incorporated in the assessment of the risks of nanotechnology, being in this regard aligned with the strategy research agenda “Nanosafety in Europe 2015-2025: Towards Safe and Sustainable Nanomaterials and Nanotechnology Innovations”. As the labour market grows, the need for new specific protocols and specialized personnel will be demanded directly by the industry to protect their workers.
NANOGENTOOLS targeted breakthroughs will likely merit publication in high-impact journals. Opting for open access publication, and accompanying such with press releases and media interview, will ensure wide dissemination of NANOGENTOOLS outcome to the scientific community and the general public, opening the field to further scientific inquiry and technological innovations.
The NANOGENTOOLS meetings, workshop and Summer School scheduled will further disseminate NANOGENTOOLS outcome to relevant stakeholders. All these will prepare the ground for the participating SMEs, well established in their respective fields, and any other entity sprouting from NANOGENTOOLS that will promote nanosafety needs. The initiatives carried out by the
academic institutions, and the consolidated role held by the participant PIs as “opinion makers” by the major national and international media (newspapers, TV/Radio channels, Nature News, etc.) will ensure proper dissemination of NANOGENTOOLS objectives, to the general public. Thus, these actions will provide a
sound proof for support provided by the EU policy to excellent research and international collaborations.
Both NIA and BioNanoNet (BNN) network structures will assure a wide impact at all their interactions levels that include a huge amount of specialized companies and national networks, in a unique multidisciplinary perspective.
8 Directory
Table 1 Directory of people involved in this project.
First Name Last Name Affiliation e-mail
Santiago Cuesta-López ICCRAM Director & Project Coordinator scuesta@ubu.es
Kalliopi Legaki NTHINX kalliopi.legaki@nanothinx.com
Francesco Dondero Università del Piemonte Orientale
"Amedeo Avogadro"
francesco.dondero@uniupo.it
Dumitru Ulieru SITEX45 R&D Director sitex45@gmail.com
Andreas Falk BIONANONET Manager andreas.falk@bionanonet.at
Iseult Sean
Lynch Kelly
University of Birmingham
Nanotechnology Industries Association
I.Lynch@bham.ac.uk sean.kelly@nanotechia.org
9 Copyright
© 2017, Universidad de Burgos (Hospital del Rey s/n -09001 Burgos, Spain) on behalf of the NANOGENTOOLS consortium.
NANOGENTOOLS is a MSCA-RISE under the Horizon2020 Programme.
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