Bioenergetics of lung tumors (ESR 1)
1) Job Summary: This PhD project will be performed in the research team directed by Dr. Rodrigue ROSSIGNOL, INSERM U1211, at the university of Bordeaux in France. The project focuses on the study on lung tumors metabolic reprogramming and bioenergetics based on preliminary findings from our laboratory Briefly, we analyzed a consistent number of surgical pieces of freshly excised human lung adenocarcinoma using bioenergetics and Omics technologies and discovered the existence of two subgroups of lung tumors characterized by a high or a low respiration, that we denominated “Ox+‟ and “Ox-‟, respectively (publication in preparation). The Ph.D trainee will study the molecular determinants of lung tumors metabolic reprograming, with a particular emphasis of oxidative tumors. Cell and mouse models of human adenocarcinoma available in the laboratory will be used to verify the role of specific signaling pathways and environmental triggers identified in the preliminary study. This PhD project includes the identification and the validation of relevant target(s) for developing anti-cancer metabolic strategies against oxidative lung tumors. Those genetic and pharmacological approaches will be evaluated at preclinical stage on orthotopic mouse models of human oxidative adenocarcinoma. Altogether, this project aims at a better understanding of lung tumors heterogeneity with implication for the development of adapted therapies.
2) Job description: The PhD candidate will analyze cell culture models of human adenocarcinoma of variegated bioenergetic profile and perform cell proteomic, cell biology, cell signaling, transcriptomic and bioenergetic experiments to decipher the determinants of the oxidative profile of lung tumors subgroup. Gene invalidation studies using shRNA or CRISPR will be conducted on those cells to delineate the role of transcription factors and kinase already identified in our preliminary studies. Those experiments will also be conducted in mouse (orthotopic model) to verify the impact of target gene invalidation / pharmacological modulation on tumor growth and survival but also metastasis and resistance to chemotherapy. Proof-of-concept and proof-of-mechanisms experiments should be generated during this project. Metabolic reprogramming of lung adenocarcinoma cells and their corresponding mouse tumors will further be deciphered using metabolomics, in collaboration with METATOOL platform (Toulouse; France). The bioenergetic analyses will be performed in collaboration with CELLOMET, a technology platform associated to our academic laboratory. As part of TRANSMIT, the PhD candidate will perform additional training in partners laboratories during the course of his/her PhD: mtDNA mutation in OX+ versus OX- tumors (Bologna, Italy); metastatic potential of OX+ versus OX- cells (Brussels; Belgium); Chemo-resistance of OX+ versus OX- cells (Stockholm; Sweden).
Principal Investigator: Dr. Rodrigue Rossignol
ESR 1: Saharnaz Sarlak
Dr. Nivea Amodeo, Post-Doc fellow