PhD project : Telomeric response to potentiate new theranostic approach in radio-resistant lung cancer cells
The project is to overcome cancer resistance by combining radiotherapy with theranostic system using AuNCs, partially modified with glycoconjugates, that will deliver siRNA targeting the telomeric protective response in lung cancer cells.
This project is organized in 4 axes. First, we will design and characterize nanosystems based on AuNCs functionalized with glycoconjugates and carrying anti-TRF2 siRNA (siAuNCs-gly). Then, the internalization and the TRF2 knock-down efficiency of siAuNCs-gly conjugates will be determined in 2D and 3D cultures of lung cancer cells. The impact of siAuNCs-gly on HNSLC cell proliferation and protective telomere response before and after X-rays exposure will be analyzed. To evaluate the potential clinical transfert, the most promising candidate siAUNCs-gly conjugate will be injected intravenously in mice bearing orthotopic lung cancer tumor to evaluate its biodistribution and its tumor accumulation.
The PhD student is expected to actively drive forward a cross-disciplinary project on theranostic approach targeting telomeric response in radio-resistant lung cancer cells. She/he will be in charge of most of a part of the experiments of the project and set up experimental protocols with the advice and assistance of the 2 co-directors of thesis (Dr Virginie Faure and Pr Olivier Renaudet). She/he will use diverse techniques such nanoparticles assembly, functionalization and characterization, 2D and 3D cell cultures, western blot analysis, RT- qPCR, immunofluorescence combined with microscopy, DNA FISH and FACS analysis. He/she will work in 2 different laboratories located both in Grenoble: the Institute for Advanced Biosciences and the Department of Molecular Chemistry. The student must therefore be able to tackle a diversity of methods and approaches. Along with performing experiments and analysing data, the candidate will also be responsible for communicating clearly and regularly the progress of the work, carry out bibliographic work, contributing to relevant national and international conferences on nanotechnology, telomeres and cancer, and writing high-quality scientific papers. She/he will also participate in collective laboratory tasks and in scientific and federating animations of the Institute. The student will have to follow courses as part of the education.
Candidates should send a Cover Letter, a CV, recommendation letters, and grade transcripts, only by email to firstname.lastname@example.org and olivier.renaudet@univ-grenoble- alpes.fr.
deadline: June 17th 2020
An interview should be organized in July 2020 for this PhD position.