Pia Kinaret is a PhD student at the Institute of Biotechnology, in the research group led by Dario Greco. She is studying alternative approaches for nanomaterial safety assessment, and has recently published an article on this topic. Congratulations Pia!
A suitable alternative for nanomaterial toxicity testing
The world is going nano! Nanoscience is a very rapidly growing field of research. Nanotechnology, nanostructure and nanoparticles are now commonplace terms and have revolutionized various aspects of our daily lives. Nanomaterials are already being used in cosmetics, cleaning products and our food, and have the potential to make supercomputers that will fit in our pockets. One very promising area is the use of nanoparticles as vehicles for drug delivery to targeted tissue sites such as tumor. But, how grave are the consequences when these particles pile up in the environment or inside us?
Technically, nanomaterials are any particles with at least one dimension less than 100 nanometers. The inherent shape and size of the nanomaterials makes them an oddball for our immune system to handle. Similar to asbestos, inhaled nanomaterials can be hazardous; cause severe asthma-type symptoms, granuloma formation, fibrosis and cardiovascular diseases. As the number of engineered nanomaterials is increasing exponentially, understanding the physiological effects of exposure to nanomaterials and developing toxicity standard for nanomaterials is of great importance. Therefore, Pia and colleagues  have studied an efficient and cost-effective method to assess nanomaterial toxicity.
The most common route of human exposure to nanomaterials is through respiration. State-of-the-art method for studying the airway-exposure of nanomaterials is via inhalation method, in which lab mice are exposed to aerosolized nanomaterial. However, this is cumbersome and time-consuming. Alternatively, this could be studied by oropharyngeal aspiration, in which the nanomaterial is introduced to animal airways as a liquid dispersion. Aspiration is much faster and cost-effective method compared to inhalation, however it is not yet clear whether the two methods are comparable.
Pia  studied the responses of lab mice exposed to carbon-based nanomaterials by inhalation and aspiration method at various doses. She found that the immune responses of the mice at low doses of aspiration were comparable to that of inhalation. Also, the responses at molecular level in terms of the gene expression changes and induced biological functions were also very similar. Pia thus concludes that aspiration is a valid alternative to the inhalation method for assessment of nanomaterial toxicity.
- Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs. Kinaret P, Ilves M, Fortino V, Rydman E, Karisola P, Lähde A, Koivisto J, Jokiniemi J, Wolff H, Savolainen K, Greco D, Alenius H. ACS Nano. 2017 Jan 24;11(1):291-303.
For the month of November 2016
Petra Tauscher is a PhD student at the Institute of Biotechnology, Developmental Biology Program with Group Leader Dr. Osamu Shimmi. She is studying the post-transcriptional regulation of TGF-beta type signaling in Drosophila development, and has recently published an article on this topic. Congratulations Petra!
Developmental patterning and intrinsic properties of BMP ligands
A fascinating area of research in biology is to understand how animals transform from a single-cell zygote to a fully-grown adult with sophisticated organ systems. Previous studies have shown that the genetic mechanisms of a huge variety of animal species during development is conserved, i.e. a similar group of genes carry out a conserved set of molecular functions. How is it possible that animals look so different, despite using the same mechanisms?
Because the developmental processes are conserved, it allows researchers to conduct studies in model organisms. For instance, invertebrates like fruit flies, as well as vertebrates use the same set of molecules for dorsal/ventral patterning (DV) during embryogenesis which ultimately determines the back/belly in adult form. The Bone Morphogenetic Protein (BMP) signaling pathway is one such conserved signaling that plays a crucial role during this process. It is also important for the posterior cross-vein (PCV) formation during pupal stage, which develops into the wings in flies. So how does the BMP signaling pathway result in DV patterning in one, and PCV in another context of development?
Previous studies suggest that changes in gene regulation affect BMP signaling in a spatiotemporal manner. Petra’s experiments  add a new aspect to this idea. She compared the protein sequences of BMP-type ligands from various species and found that the BMP-type ligands contain a highly conserved N-glycosylation motif. However, Screw, a BMP-type ligand in fly, carries an additional unique N-glycosylation motif that is not present in other BMP-type ligands. While Screw is critical and exclusively found in the context of dorsal/ventral patterning, Glass bottom boat, a paralog of Screw plays a role during PCV formation in fly. Petra et al. found that Screw, if expressed artificially in the wing can replace the function of Glass Bottom Boat during PCV formation, but vice-versa is not true. Furthermore, BMP-type ligands lacking N-glycosylation motifs were more efficient in the context of PCV formation, whereas lack of N-glycosylation in the Screw ligand led to a reduced viability. This suggests that N-glycosylations provide an advantage for DV patterning, i.e. during early stages of embryogenesis but are detrimental during PCV formation. Hence, N-glycosylation motifs affect BMP function in a context dependent manner.
Petra thereby concludes that apart from the spatial and temporal changes in gene expression, post-translational modifications may be one way how evolutionarily conserved molecules and signaling pathways adapt to different developmental processes.
- Tauscher PM, Gui J, Shimmi O. Adaptive protein divergence of BMP ligands takes place under developmental and evolutionary constraints. Development. 2016 Oct 15;143(20):3742-3750.