Reference : UMR5095-KILAUD-004
Nombre de Postes : 1
Workplace : BORDEAUX
Date of publication : Monday, November 28, 2022
Type of Contract : FTC Scientist
Contract Period : 11 months
Expected date of employment : 1 February 2023
Proportion of work : Full time
Remuneration : between 2805.35 and 3224.81 euros gross per month depending on experience
Desired level of education : PhD
Experience required : 1 to 4 years
The post-doctoral student will be responsible for carrying out research activities in the framework of the THEMA project. This project has strong biomedical implications. The biological context will be the control and regulation of cell energetic metabolism, significantly in the context of carcinogenesis. This metabolism regroup all the processes involved in ATP synthesis, glycolysis in the cytosol and oxidative phosphorylations (OXPHOS) in the inner mitochondrial membrane. Metabolic rearrangements occur in cancer cells : mitochondrial OXPHOS are repressed and fermentation (glycolysis) is increased together with cell proliferation. This process has been evidenced by Otto Warburg and hence is referred to as the Warburg effect. Mitochondrial quinones (ex. Q10) are small lipophilic molecules, located in the mitochondrial inner membrane, mobile in the respiratory chain where they carry electrons between the respiratory complexes. The quinone redox state depends on the respiratory chain capacities to reoxidize its reduced substrates and the availability of oxygen. An incomplete reduction of oxygen will lead to reactive oxygen species (ROS) formation that induces a mitochondrial and cellular redox stress. Altogether these elements suggest that the mitochondrial quinone redox state could be an excellent marker of the cellular redox state and the cellular oxidative stress in physio and pathological conditions. The candidative will thus develop an analytical method to assess the mitochondrial quinones redox state at different integration levels: isolated mitochondria, permeabilized cells and whole cells.
Preliminary work in our lab in collaboration with Dr Arbault's team (CBMN, UMR5248 CNRS, Univ. Bordeaux), have shown that an electrochemical analysis of the quinones redox state is efficient on isolated yeast mitochondria. This work will be the foundation of the work to be developed by the post doc researcher.
Analytical Chemistry, 2013, 85, 5146 ; Angewandte Chemie-Inter. Edit, 2014, 126, 6773; Analytical & Bioanalytical Chemistry, 2014, 406, 931; Electrochimica Acta, 2014, 126, 171; Analytical Chemistry, 2016, 88, 6292; J. Biol. Chem., 2018, 33, 12843 ; J. Am. Chem. Soc., 2018, 140, 14753; Biosensors & Bioelectronics, 2019, 126, 672; Cells, 2019, 4, 287; Cellular Molecular Life Sciences 2020, 3, 455; Frontiers In Oncology, 2020, 10, 1333; Mitochondrial Medicine: Methods and Protocols, Vol. 2, 2021, p 153 – 163
- The candidate will perform mammalian cell cultures, assess their energetic metabolism (glycolysis and OXPHOS activities) together with studying their quinones redox state by electrochemistry. This will be done at different integration levels: isolated mitochondria, permeabilized cells and whole cells.
- The candidate will develop an electrochemical measurement of the quinones redox state on whole living cells. The study will be based on the development of electrochemical methods and sensors for quinones and ROS production. The characterization of mitochondrial quinones state will be correlated to the one of other reduced molecules such as NADH and glutathione. Next, the role of this redox state in the Warburg effect physiopathological process will be analysed and modulated to determine its importance and relevance as a therapeutic target. Such analyses could eventually be used as a pharmacological screening approach.
Skills / knowledge
- Cell energy metabolism
- OXPHOS control and regulation
-Cell culture, oxygraphy, electrochemistry, spectrophotometry
-bibliography, publication redaction
- Ability to work in teams and collaborative projects
- Writing skills, ability to formulate a scientific project, to publish and promote research
- Autonomy, organizational skills and accountability
- Good interaction with collaborators
The "Institut de Biochimie et Génétique Cellulaires" (IBGC) is a fundamental research institute dedicated to the study of cellular functions using yeast, fungi, mammalian cells, drosophila and nematode as biological models.
Mitochondrial functions and dysfunctions are studied. They encompass a wide array of topics including cell biology aspects such as fusion-fission dynamics, as well as bioenergetics and structural studies connecting the respiratory chain organization to mitochondria biogenesis and ultrastructure. The role of mitochondria in normal or pathologic functions such as apoptosis and cancer is investigated. Yeast models of genetic diseases have been developed and used for drug screening.
Cell cycle in yeast models and drosophila is also a major field of interest. Mechanisms allowing proper chromosome transmission are questioned as well as polarity establishment and cellular rearrangements upon quiescence entry/exit. The mechanisms connecting cell growth to the cell cycle and to nutriment availability are also scrutinized.
Protein structures responsible for cell death or pathologies are explored: by using yeast as a model to study Aβ folding and the cellular bases of its toxicity. By exploring specific protein structures responsible for programmed cell death and other cellular responses associated with detection of non-self in the original Podospora anserina model.
Approaches, including biochemistry, cell biology and genetics are commonly used by most of the groups. Methodologies and technologies used in the IBGC are highly diverse, including crystallography, electron microscopy, live cell imaging, chromatography etc, all techniques being generally combined with molecular genetics.
The post-doctoral fellow will be part of Dr Anne DEVIN's team.
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