Early Stage Researcher (ESR/PhD) in the Marie Skłodowska-Curie ITN European Training Network “TRANSMIT – TRANSlating the role of Mitochondria in Tumorigenesis” (H2020-MSCA-ITN-2016) - ESR 1 (University of Bordeaux, France)
TRANSMIT - TRANSlating the role of Mitochondria in Tumorigenesis
The consolidation of the knowledge that cancer is not only a genetic, but also a metabolic disease, has led scientists to investigate the intricate metabolic plasticity that transformed cells must undergo to survive the adverse tumor microenvironment conditions, and the contribution of oncogenes and tumor suppressors in shaping metabolism. In this scenario, genetic, biochemical and clinical evidences place mitochondria as key actors in cancer metabolic restructuring, not only because these organelles have a crucial role in the energy and biosynthetic intermediates production but also because occurrence of mutations in metabolic enzymes encoded by both nuclear and mitochondrial DNA has been associated to different types of cancer. TRANSMIT aims to dissect the metabolic remodeling in human cancers, placing the focus on the role of mitochondria and bridging basic research to the improvement/development of therapeutic strategies. Further, TRANSMIT fosters the communication of this emerging field to the patients and their families. To these aims, TRANSMIT will create a network of seven different countries, among which world-leading basic science and clinical centers of excellence, several industrial partners with up-to-date omics technologies, as well as non-profit foundations and associations who care for cancer patients. By creating the critical mass of scientific excellence, TRANSMIT will allow to transfer the current knowledge into the wide field of cancer research, translating scientific and technical advances into the education and training of eleven Early Stage Researchers. TRANSMIT will implement training-through-research dedicated to unravel the metabolic features of cancer, as well as to provide a full portfolio of complementary skills through the creation of a network of basic, translational and industrial laboratories, devoted to a multidisciplinary/multi-sectorial education of young scientists.
1) Job Summary
This PH.D 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 PH.D 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).
Subject area of PhD program in which the ESR will be enrolled and PhD program duration
Ph.D in Biochemistry (3 years).
3) Host University that will provide the PhD degree
University of Bordeaux (Bordeaux; France)
4) PhD program starting date: 01/10/17
Required Educational Level
Degree Field: Biochemistry / Cell Biology / Molecular Pathophysiology
Knowledge: good level in biochemistry, cell signaling, mitochondrial physiology and energy metabolism pathways. Good notions in cancer biology and in lung physiology are also required.
Methods: cell culture (mammalian cells), siRNA/shRNA transfection, lentiviral plasmids production/transduction, polarography, fluorescence microscopy, westernblot, immunoprecipitation, immunocyto/histo-chemistry, Omics sample preparation and data analysis (IPA software…). Experience in mouse models of cancer is appreciated: tumor size follow-up by bioluminescence imaging, drug/cells injection, necropsy and tissue sampling for histology, proteomics and biochemical analyses.
Personality: strong motivation in cancer research, autonomy and respect of other team members.
Applicant should be fluent in written and spoken English
Applications, in English, should include CV, detailed academic transcripts, a copy of the thesis, a motivation letter and a reference letter, which are all to be submitted by email to firstname.lastname@example.org
*Elegibility: The applicants must be in possession of a degree in Biochemistry or Cell Biology and Molecular Physiology at the date of recruitment - an ‘early stage researcher’ (i.e. in the first four years of his/her research career and not have a doctoral degree).
The applicant may be a national of a Member State, of an Associated Country or of any other Third Country.
The applicant should not have resided in the country where the research training activities take place for more than 12 months in the 3 years immediately prior to the recruitment date and not have carried out their main activity (work, studies, etc.) in that country.
· Enrollment in a PhD school in a specific area
· 3-year employment contract: net salary of 3253 euros + 416 euros net of family allowance (if applicable)
· A highly multidisciplinary, cross-cultural and competitive training program in the field of metabolism in cancer (or molecular oncology)
· Secondments and a specific training program
· Vacation days/year:
First selection step: Curriculum evaluation. Numerical scores will be awarded for grading criteria such as study marks, duration of study, scientific publications in peer reviewed journals, reference letters. Only the admitted candidates will be contacted by e-mail for the second selection step.
Second selection step: Skype or face-to-face interview in which candidates will give a short presentation of their master thesis and of a scientific paper that they will receive three weeks before the interview.
Evaluation period: none.