Project 5 (NERC)
Project 5: Investigating the role of metal binding protein in nanotoxicology using a laboratory model organism
Fellow: Carolin Schultz (ESR5), 36 months
Tutors: Dr. Claus Svendsen (NERC)
The unique characteristics of many of the engineered NP used in nanotechnology products are achieved by design through their small size and/or fuctionalisation. While these unique properties give the particles their particular qualities, they also raise concerns that NP may confer unforeseen toxicity to exposed organisms (including humans) following release into the environment. To ensure the safe application of nanotechnology, a better understanding of the exposure and toxicity of manufactured nanomaterials in the environment is needed.
To establish the modes of action of NP toxicity, a PhD project performed by an ESR will utilize the nematode model organism to conduct baseline studies to evaluate the toxicological effects of different samples of Ag as well as other metal and metal oxide based synthetic NP on life-history traits, fitness and metabolism. The hypothesis is that exposure to NP will elicit toxic responses that are beyond those that are observed in nematodes exposed to similar molar concentrations of metals and metal oxides in ion and bulk forms. This work will provide an in vivo element to the NanoTOES network that will serve to validate and support in vitro studies within other projects. To further investigate the mechanisms involved in NP toxicity in the nematode, microscopy approaches using light, electron and RAMAN instrument studies of the toxicokinetics of NP will be used to assess the adsorption and distribution components of toxicokinetics. This work will investigate whether any added toxicity associated with exposure to NP forms can be directly attributed to toxicokinetic parameters for particles. To further investigate the metabolism and excretion components of toxicokinetics, the project will also analyse expression change with major pathways know to be involved in the detoxification of toxic metals, such as metallothioneins and phytochelatin synthase using quantitative PCR. Finally, RNAi will be used to assess the contribution of key genes in the toxicogenomic response to NP and GFP-staining will be used to assess spatial localisation of such effects around particles in situ (KCL). This later work will provide essential confirmation of the role of particular biochemical pathways in the accumulation, distribution and elimination of NP exposure and address the issue of local tissue damage hotspots around particles.
Main skills acquired will be in in vivo toxicology, molecular biology, functional genetics and the use of advanced microscopy methods for the characterisation of NP both in environmental media and in vivo. Secondments to partners 1 (reporter gene methods), 6 (comparing health and ecotox data), and 9 (methods for NP visualisation in biological entities).
In WP1 (tasks 1.1 and 1.3), WP2 (tasks 2.3 and 2.4), WP3 (task 3.4) and WP4 (task 4.1).