Project 10 (ACS)
Project 10: Standardised assay platforms for cell-based nanosafety testing
Fellow: Dr. Mun Li Yam (ER1), 24 months
Tutor: Dr. Colin Wilde (ACS)
AvantiCell Science’s contribution shall be a two-year project, undertaken by an ER appointee, which shall produce cell-based assays validated for their ability to predict toxicological responses to nanoparticles under a range of sample-presentation conditions. The assays shall be designed to measure cytotoxicity of NP selected by project partners and presented in a variety of standardised forms; for example it is anticipated that medium- to high-throughput methodology will facilitate the systematic evaluation of forms of silver or silica NP generated by partners 9 (ICN) and 12 (Bayer). The intention shall be to demonstrate a robust methodology which shall be distributed amongst project partners for evaluation, and thereafter to third-party laboratories for beta-testing, with assay systems being refined based on user feedback. This process shall have two intended outputs. First, assays developed under the project shall be designed to be eligible for ECVAM accreditation in the area of nanotoxicity testing; second, assays shall be sufficiently user-friendly to have commercial potential, and be attractive for licensing by service/product suppliers active in the relevant industry sector.
AvantiCell’s assay development shall primarily focus on the building of a robust assay platform from elements already available within the company. Accordingly, assays shall make use of human primary cells, which are a principal, distinctive feature of AvantiCell’s technology base. A key cell type for assay development shall be the human hepatocyte, which AvantiCell has available in a form capable of population expansion and banking, without loss of differentiated function. Second, assays shall, as appropriate, incorporate 3-dimensional cell-culture technology, which can serve to enhance the performance of primary cells in culture. Third, assays shall be delivered with a simple, user-friendly readout, but be developed to allow, alternatively, high-content outputs in the form of cell-proteomic profiling. This methodology, proprietary to AvantiCell, shall enable cell screening for subtle changes associated with nanoparticle exposure, which may not be evident in the principal fluorescence-based cytotoxicity assay readout.
AvantiCell shall, in the course of the project host visits by appointees from other partner. The objective of those visits shall be to provide insight into, and to advance in practical terms, the translation of research laboratory cell-based methodologies into systems capable of wider dissemination to third parties or, indeed, commercial application. This training shall focus on development of Standard Operating Procedures (SOPs) and the comprehensive validation and robustness testing associated with the realisation of an assay capable of accreditation to the standards of Good Laboratory Practice (GLP). The ER appointee will make secondment visits to partners 1 (PLUS), 2 (CNR) and 3 (Fraunhofer) for training in complementary cell-reporter, immunological and biochip methodologies for cell-based analysis.
In WP1 (task 1.5) and WP4 (tasks 4.1 and 4.5).