Project Work Packages
Work packages (WP) structuring the major scientific objectives indicated in section B.1.2. of the Description of Work (Annex I):
|There are 6 Work Packages (WPs) in the project NanoTOES, organized in Tasks as follows:|
|WP/Task||WP title (involved Partners)|
|General cellular and molecular reactions triggered by NP (CNR)|
|1.1||Changes in cellular and macromolecular structures/functions in response to interaction with NP (effects on proteins, proliferation, cellular stress, cell death, etc.) (PLUS, CNR, Fraunhofer, UCD, IEM-HAS, ACS, NERC, Grimm)|
|1.2||Cellular uptake mechanisms for different types of NP (UCD, IEM-HAS)|
|1.3||Interaction of NP with subcellular organelles (mitochondrial functions, protein synthesis, lysosomal/endosomal/proteosomal accumulation, etc.) (Fraunhofer, UCD, NERC, IEM-HAS)|
|1.4||Interaction of NP with DNA (NILU)|
|1.5||Effects of NP contaminants (LPS, metals, allergens, etc.) and NP-related agents (Ag sols, Ag solutions etc.) (PLUS, CNR, IST, ICN, Grimm)|
|Cell- and tissue-type specificities in reactions to NP (IEM-HAS)|
|2.1||Cellular responses reflecting effects on the immune system, role of Reactive Oxygen Species in NP/immune interaction (PLUS, CNR, NILU, IST)|
|2.2||Detection of DNA damage and responses of the DNA repair mechanisms (NILU)|
|2.3||Functional role of metal binding protein in NP toxicosis (NERC)|
|2.4||Reactions of barrier/transport interfaces: epithelial cells from lung, intestine (PLUS, CNR, NERC)|
|2.5||Reactions of neural tissue-type cells and neural barrier (blood-brain, liquor-tissue, myelin) interfaces (PLUS, CNR, IEM-HAS)|
|The fate of NP in contact with biological systems (ICN)|
|3.1||Novel methods for detection of NP within living material (UCD, IEM-HAS, ICN)|
|3.2||Degradation, coating, clustering, aggregation and sedimentation of NP (PLUS, IST, ICN, Bayer)|
|3.3||Evolution of interaction: NP changes over time (CNR, IST, ICN, Bayer)|
|3.4||Toxicokinetics of NP accumulation and distribution (NERC)|
|Conclusions on markers and toxicity endpoints for assessment of NP safety (NILU)|
|4.1||Biomarkers of cytotoxicity (PLUS, Fraunhofer, NERC, ICN, ACS)|
|4.2||Biomarkers of oxidative stress, NP effects on the different pathways leading to stress (PLUS, CNR, UCD, NILU)|
|4.3||Biomarkers of inflammation and immunotoxicity (PLUS, CNR)|
|4.4||Biomarkers of genotoxicity (NILU)|
|4.5||High throughput and on-site screens (PLUS, Fraunhofer, UCD, NILU, IST, ACS, Grimm, Bayer)|
|Implementation of the training pathway (PLUS and all other partners)|
|5.1||Recruitment of fellows|
|5.2||State of the art in nanotoxicology, basic and widely used approaches (all)|
|5.3||Working according to GLP guidelines, validation of results and methods (all)|
|5.4||Translating key research methodologies into validated, standardised assays that provide robust screening tools (all)|
|5.5||Dissemination to the scientific community, nanosafety testing laboratories, nanomaterials producers or users, regulatory agencies, general public and media; production of textbook on nanotoxicology (all)|
WP1 to WP4 contain the scientific work carried out in within NanoTOES, arising from the project concepts and
objectives. In turn, the concrete realization of the work required in these WPs is carried out throught the individual Research Projects of the fellows.
WP1, comprising objectives 1 and 2: Assessment of general cellular responses and the molecular mechanisms involved upon exposure of cells, tissues and invertebrate model organisms to NP. Correlation of biological endpoints with NP characteristics: composition, size, shape, coating.
WP2, comprising objective 3: Determination of cell- and tissue-specific reactions for important target sites (lung, intestine, neural tissue, immune cells, etc.). Distinction between general and cell-specific biomarkers, tissue-specific responses in an invertebrate model. Validation and refinement of appropriate methods to allow a comprehensive safety assessment with the aim of reducing risks to human health and the environment.
WP3, comprising objectives 4 and 5: Identification of factors (physical, chemical, biological) which affect NP during storage and handling, and during biological interaction, reducing the toxicity potential of the latter. Analysis of NP effects on living systems, and vice versa assessment of the changing properties of NP in the presence of biological compounds, cells and tissues, taking into account the role of bystander substances.
WP4, comprising objective 6: Definition of valid biomarkers for a comprehensive safety assessment of selected economically-relevant nanomaterials, using silver nanomaterials as standard materials, while evaluating at the same time the experimental conditions required to obtain reliable conclusions on safety towards health and environment. This objective, to which every partner contributes, will allow the development of commercially feasible methods and equipments for practical applications and will validate laboratory methods under real-life conditions.