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NANOSAFETY
UCD’s expertise in nanosafety includes trafficking, pathways, cellular uptake, screening.  We have particular expertise in running assays for cytotoxicity and are active in regulatory discussions around nanosafety.

PROFILE:
Neuro-toxicology
Lead PI: Prof Kenneth Dawson/Dr Iseult Lynch
Neurodegenerative diseases currently affect over 1.6% of the European population,(Alzheimer Europe 2006) with dramatically rising incidence likely (in part) due to the increase of the average age of the population. The overall science and technological objective of the NeuroNano program is to determine if engineered nanoparticles could constitute a significant neuro-toxicological risk to humans for two diseases endpoints, Alzheimer’s and Parkinson’s diseases. The emphasis on mechanisms is important for it will advance the field of knowledge of neuronanotoxicology, irrespective of whether any clear disease endpoint emerges. The data generated within the NeuroNano program will be consolidated into a deeper understanding of the risks posed by nanoparticles in terms of human health, disease and in particular neurodegeneration.

http://www.ucd.ie/cbni/projects/european-projects/neuronano/

Modeling relationships between nanoparticle properties and toxicity
Lead PI: Prof Kenneth Dawson/Dr Iseult Lynch
NanoTransKinetics main objective is to establish techniques for modeling relationships between nanoparticle properties and toxicity (including interactions of nanoparticles with biological systems). The project focuses on understanding the mechanisms of nanoparticle uptake into, and sub-cellular transport within cells and through biological barriers with the objective of enabling much more rapid progress towards a screening approach, where predictions of nanoparticle bioaccumulation could be made on the basis of limited in vitro screening data.

http://www.ucd.ie/cbni/projects/european-projects/eu-us-nanotranskinetics/

High content imaging of nanoparticle uptake in cells
Lead PI: Prof Kenneth Dawson/Prof. Jeremy Simpson
Despite the increased application of nanomaterials in diagnostics and therapeutics, methods to study the interactions of nanoparticles with subcellular structures in living cells remain relatively undeveloped. The UCD Cell Screening Laboratory developed a robust and quantitative method that allows for the precise tracking of all cell-associated nanoparticles as they pass through endocytic compartments in a living cell. The Dawson and Simpson groups have shown that following internalization, 40 nm polystyrene nanoparticles first pass through an early endosome intermediate decorated with Rab5, but that these nanoparticles rapidly transfer to late endosomes and ultimately lysosomes labeled with Rab9 and Rab7, respectively. Larger nanoparticles of 100 nm diameter also reach acidic Rab9- and Rab7-positive compartments although at a slower rate compared to the smaller 40 nm nanoparticles. This work also revealed that relatively few nanoparticles are able to access endocytic recycling pathways, as judged by lack of significant co-localization with Rab11. This quantitative approach is sufficiently sensitive to be able to detect rare events in nanoparticle trafficking, specifically the presence of nanoparticles in Rab1A-labeled structures, thereby revealing the wide range of intracellular interactions between nanoparticles and the intracellular environment.

Sandin P, Fitpatrick LW, Simpson JC, Dawson KA, High-Speed Imaging of Rab Family Small GTPases Reveals Rare Events in Nanoparticle Trafficking in Living Cells, Acs Nano, vol6 (2) 1513.(PDF)