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The European Synchrotron, the ESRF, is an international research centre based in Grenoble, France.
Through its innovative engineering, pioneering scientific vision and a strong commitment from its 700 staff members, the ESRF is recognised as one of the top research facilities worldwide. Its particle accelerator produces intense X-ray beams that are used by thousands of scientists each year for experiments in diverse fields such as biology, medicine, environmental sciences, cultural heritage, materials science, and physics.
Supported by 19 countries, the ESRF is an equal opportunity employer and encourages diversity.
Thesis subject: Impact of mutations in the MT-CO1, MT-CO2 and MT-CO3 genes on the structure of mitochondrial Complex IV: role in chemoresistance of acute myeloid leukaemia
You will join the MXIS group at the ESRF and the Institute for Advanced Biosciences at UGA (iab-grenoble.fr) to study how mutations in the mitochondrial genes MT-CO1, MT-CO2 and MT-CO3 contribute to mitochondrial dysfunction and chemoresistance in acute myeloid leukaemia.
At the ESRF, the project will focus on the structural characterisation of Complex IV and associated respiratory assemblies from leukemic mitochondria. SAXS and cryo-EM will be used to compare mutated and non-mutated systems, with particular attention to assembly state, heme/cofactor environments and supercomplex organisation.
At the IAB, the project will examine the transcriptomic and functional impact of these mutations, before and after cytarabine treatment. RNA-seq and mitochondrial phenotyping will assess pathways linked to heme/iron metabolism, OXPHOS, redox stress, apoptosis and ferroptosis.
By integrating these structural, transcriptomic and functional data, the ESRF-IAB collaboration will build a mechanistic model linking MT-CO-driven Complex IV remodelling to altered mitochondrial homeostasis and reduced cytarabine sensitivity. Expected outcomes include optimised workflows for structural studies of leukemic mitochondrial assemblies, curated multi-modal datasets and new insights into AML chemoresistance.
Further information may be obtained from J. Mondet ([email protected]) or M. Soler-Lopez ([email protected]).
Your shall be enrolled in UGA University / EDCSV Doctoral School as a condition of your hiring.
Contract of two years renewable for one year.
Do you recognize yourself in this description? Apply now for your next professional adventure!What we offer:
The ESRF is an equal opportunity employer and encourages applications from disabled persons.
Operate and develop ID27 high-pressure X-ray diffraction beamline; support international users, run extreme P/T experiments (DAC, large-volume press), and pursue in-house research. 5-year contract.
The ESRF is an X-ray light source for Europe. It is located in Grenoble, France, and supported and shared by 20 countries.
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