Sophie Grellet (ESR 12)

Exploring site specificity, structure and sequence dependence of radiation-induced damage

Project description:
Radiotherapy is currently used in around 50% of cancer treatments. Although it is highly effective, it is damaging to surrounding healthy tissues and needs to be improved by better targeting to cancer cells. Improved radiotherapy outcomes can be achieved by targeting heavy elements (like AuNPs) to cancer cells, since these locally amplify the damage caused by radiotherapy.

The cancer cells targeting and particularly the uptake of AuNPs are highly influenced by their coating and in this way, especially by their charges. Positively charged AuNPs are thought to have improved cellular uptake because of their interactions with the negatively charged lipid membrane or the glycocalyx structure, which can be more pronounced on cancer cells. However, there are still controversies on the exact properties of the AuNPs to maximise uptake.

I will investigate the relationship between AuNPs charges and cellular uptake and toxicity on cell models (in vitro). Reactive oxygen species (ROS) production, mechanism of cell death and localization in cells will be explored on different types of in vitro cancer and normal cell models. The best AuNPs will be combined with radiotherapy (X-ray radiation at Northampton Hospital). Then, different coating of AuNPs, especially for amplifying DNA targeting, will be explored to improve not only the uptake on cancer cells, but also the effect in combination with radiotherapy. This work will be done in collaboration with other ESRs.


Short CV
Education:
July 2014: Doctor of Pharmacy graduation
2013-2014: Master's degree in Toxicology, research-oriented, at University Paris Descartes
2012-2013: Day school of Pharmacy at Louis Mourier Hospital (Colombes)
2011-2012: First year of Master's degree in Environmental risks and Public health
Work experience:
2014: 6 months Master's degree internship at INERIS with Ghislaine Lacroix, within TOXI unit
2013: 3 months internship within the framework of the Industry sector, in Ecotoxicology Laboratory of Gothenburg, with Joachim Sturve
2012: 2 months internship in the first year of Master's degree, in Public health laboratory of University of Paris Descartes, environmental toxicity specialty, with Sophie Achard