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Functional Impacts of Nanoparticles

Although there have been some suggestions on how nanoparticles perturb signalling pathways within CBNI we seek an unbiased assessment of the functional impacts of nanomaterials. 

Activation and time-resolved exploration of individual pathways in a serial approach is being used in the first instance for a selected range of end-points, including apoptosis, autophagy, and genotoxicity, with the aim of establishing appropriate positive and negative control nanomaterials, which will form a basis for regulatory approval.

Approaches being used to tease out signalling pathways disrupted by the cellular uptake and accumulation of nanoparticles include assessment of changes in protein and gene expression in exposed cells (proteins via ELISA and mRNA via RT-PCR) as well as utilising proteomics and redox proteomics to assess nanoparticle-induced changes in protein expression.  More recent efforts include the use of mRNA silencing approaches to selectively knock-out selected proteins along an uptake pathway and correlation with efficacy of nanoparticle uptake.

Bexiga, M.G., Varela, J.A., Wang, F., Fenaroli, F., Salvati, A., Lynch, I., Simpson, J.C., Dawson,

K.A. Cationic nanoparticles induce caspase 3-, 7- and 9-mediated cytotoxicity in a human astrocytoma cell line. Nanotoxicology. 2010 Dec 13. [Epub ahead of print]

Slavov, S, Dawson, KA.  Correlation signature of the macroscopic states of the gene regulatory network in cancer, PNAS, 2009, 106, 4079-4084.