PhD Student- GATES

Context & Job description

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 (JMondet@chu-grenoble.fr) or M. Soler-Lopez (solerlop@esrf.fr).

Expected profile

• Degree allowing enrolment for a PhD (such as MSc, Master 2 de Recherche, Laurea or equivalent) in chemistry, biology or closely related science
• A background in molecular biology, structural biology, and bioinformatics would be considered an asset
• Proficiency in English (working language at the ESRF)

Working conditions

Your shall be enrolled in UGA University / EDCSV Doctoral School as a condition of your hiring.

Contract of two years renewable for one year.