Bengt Fadeel of the Karolinska Institutet spoke about the possibilities of using transcriptomics — gene expression profiling — to aid in the prediction of mechanisms of toxicity. By coupling global “omics” technologies with computational approaches to determine significant perturbations of genes or pathways, one can identify the potential hazards and mechanisms of action of ENMs. Fadeel provided some examples of the techniques that could be used to do this, with a particular focus on nanomaterial effects on immune-competent cells.

 

Juha Kere, also of the Karolinska Institutet, described some new approaches to transcriptomics. Transcriptomics can be used to study to study gene expression The most commonly used RNAseq techniques capture sequences along transcripts, but alternative methods focus on the ultimate 5’ ends of transcripts, allowing the specific definition of transcription start sites (TSSs). Kere and colleagues have adopted and developed one such method, known as single-cell tagged reverse transcription (STRT). The method is highly sensitive at the single cell transcriptome level, but is equally well applicable to small RNA samples. It is robustly applicable to nanosafety research because of high sensitivity, the low amount of RNA needed, assessment of technical and biological variation in experiments, and low cost. Once marker TSSs become identified by STRT or similar methods, targeted assays can be developed for nanosafety assessment purposes using alternative specific, validated, streamlined and economical methods.

 

Riitta Lahesmaa of the University of Turku Regulation of the immune response is essential to human health. T cells in particular orchestrate the adaptive arm of the immune system and are required for key immune functions. T helper cell subsets with a distinct cytokine secretion profiles and function play a crucial role in host defence as well as in pathological disorders such as allergy and chronic inflammatory and autoimmune diseases. These in turn can be modulated by different stimuli such as nanoparticles either directly or through the effects on the innate immune cells. Lahesma explained how the use of a systems biology approach has revealed new regulators of lymphocyte responses including factors involved in signalling, transcriptomics and epigenetics.

 

Egon Willighagen finished with a short presentation on the eNanoMapper project, which develops computational solutions to support the development of new ENMs within the European community. These solutions are based on a proposed common ontology, to unite the research done within the nanosafety domain. This common language is based on reusing existing ontologies, like the NanoParticle Ontology (NPO), and developed in collaboration with other projects from the NanoSafety Cluster, but also by collaborating with other partners from inside and outside of Europe.

 

Another important component is the database approach. eNanoMapper selected the open and flexible OpenTox platform which has been extended to support nanomaterials: the user will find information including experimental data, physico-chemical and biological nanoparticle characterisation.

By combining these two components and adopting open standards, such as ISATab-Nano, eNanoMapper is able to make user-oriented applications to support the day-to-day work of researchers in the community.

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Session 3