Metabolic and epigenetic reprogramming in glioma cells
Dates:1 September 2016 - 31 December 2016
Date limite de candidature:1 September 2016
Lab rotation proposal: 3 months
~ Sep-Dec 2016 ~ Jan-March 2017 ~ Apr-June 2017
Strongly altered cellular metabolism is a common feature of cancer cells, and participates in their development and maintenance. We performed metabolome profiling of cancer stem cells isolated from glioblastoma (GSC) prior and after expression of the micro-RNA cluster miR-302-367 that inhibits GSC stem and tumour-initiating properties (Fareh et al, Cell Death & Diff 2012). We identified unexpected rearrangements of several metabolic modules linking epigenetic regulations and cancer features, and pinpointed specific metabolic pathways that undergo reprogramming following the exit of GSC from their stem state. We further showed that mimicking these metabolic reprogramming through genetic and pharmacological manipulations oppose cancer features in glioblastoma stem cells isolated from patient brains presenting distinct genomic anomalies (manuscript in preparation)The objectives of our project will aim at:- Deciphering the fine molecular mechanisms by which these rearrangements in metabolic modules affect the epigenetic regulations observed. This will be achieved using cell biology, biochemistry and molecular biology technics combined with bioinformatics analysis of data sets integrating the metabolic, genetic and epigenetic changes in the cells submitted to modulation of the metabolic module under scrutiny.- Evaluating the clinical relevance of the findings. This will be achieved by in vitro sphere assays and animal models of glioblastoma combined with BRET or FRET luminescent sensors to monitor the metabolic state of the cells in live animals.
Address: Neuroscience Paris Seine - Université Pierre et Marie Curie 7-9 quai Saint Bernard 75005 Paris
Phone number: +33 1 44 27 33 65 ; Mail: email@example.com