Freya Joris

Freya Joris

Contact

Freya Joris
PhD student, Pharmacist
Laboratory for General Biochemistry and Physical Pharmacy
Ghent University
Harelbekestraat 72
9000 Gent
Belgium
Tel: 0032 9 264 8047 (secretary)
Tel: 0032 9 264 8095 (direct)
Fax: 0032 9 264 8189
E-mail: freya.joris@UGent.be

Biography

After obtaining a Bachelor degree in Pharmaceutical Sciences in 2010, she graduated as a Master of Science in Drug Development in 2012 from the VUB. The same year she started a PhD at the Lab of General Biochemistry and Physical Pharmacy at Ghent University for which she received a scholarship from the IWT. The focus of this PhD lies on the optimization and development of in vitro protocols for studying nanotoxicity.

Summary of Research Project(s)

The number of newly engineered nanomaterials is vastly increasing along with their applications. Even though a lot of interest and effort is being put into the development of nano-based biomedical applications, the level of translational clinical output remains limited due to uncertainty on the toxicological profiles of the nanoparticles (NP). As NP in biomedical devices are likely to directly interact with cells and biomolecules it is imperative to rule out any adverse effects and obtain a thorough toxicological characterisation of the NP before they can be safely applied. It is known that the adverse effects of NP are correlated to their physicochemical properties such as size, charge, surface area etc. Still the generation of more data on the subject has not enabled researchers to draw firm conclusions on the correlations between the toxic effects and the physicochemical properties as this is strongly impeded by conflicting results from multiple studies. Consequently, acquiring more consistent and relevant toxicological data becomes a necessity but the incentive to reduce the number of animals used for in vivo toxicity testing also has to be taken into account. Therefore the need for more reliable in vitro models with a higher predictive power, mimicking the in vivo environment more closely, becomes more prominent.

In order to establish a correlation between in vitro and in vivo data, optimisation of in vitro models is essential, which includes the standardization of the study design and overcoming the shortcomings inherent to the most used classical 2D monocultures. The aim of this PhD work is to study the influence of the shortcomings to classical culture models on NP induced injury, using several novel model systems and propose recommendations on how the classic protocols could be improved in order to bridge the in vitro-in vivo gap.

To meet the lack of standardization and in order to enable a comparison of the models that will be proposed in this work, every model will be evaluated according to the same multiparametric method that was previously drafted by our group 1. Hereby acute toxicity, ROS induction, morphological changes, cellular functionality and NP degradation will be evaluated, using mainly biochemical and microscopic methods as these methods are easily amendable for future high content screening approaches. First we will verify whether cancer cells and long-lived cell lines are useful models compared too primary cells, which are much harder to obtain but physiologically more relevant. NP are administered to the cells as a dispersion and are prone to effects like sedimentation and ion leaching in this environment. Since these effects do not appear in vivo, their influence on the toxicity will subsequently be evaluated in a vertical and flow system. To further bridge the in vitro-in vivo gap, more sophisticated models are needed as cell-matrix effects, intercellular communication and tissue organization are unaccounted for in classical 2D monocultures. Therefore the behaviour of the NP (cellular distribution...) and their toxicity will be evaluated in a co-culture and a 3D model. By combining our findings we expect to be able to evaluate to which extent classical 2D models are a reliable representation of the in vivo situation and will suggest modifications in order to optimise the current nanotoxicology methods.

Freya Joris research project

(1) S. J. Soenen, B. Manshian, J. M. Montenegro, F. Amin, B. Meermann, T. Thiron, M. Cornelissen, F. Vanhaecke, S. Doak, W. J. Parak, S. De Smedt and K. Braeckmans, ACS nano, 2012, 6, 5767-5783.