mitochondrial syndrome COXPD23 associated with cardiomyopathies or encephalopathies. The enzymatic reaction requires a complex set of cofactors and substrates including GTP, FAD, NADH, taurine and a folate derivative. Currently, the enzymatic mechanism, structural organization, and cellular consequences of the corresponding pathological mutations in GTPBP3 and MTO1 remain poorly understood.
In this proposed Ph.D. project, the candidate will pursue two main objectives: (1) reconstitute the tRNA modification pathway in vitro to define catalytic steps and assess the impact of clinical variants through biochemical techniques; (2) resolve the structural basis of enzyme cooperation using biophysical tools, X-ray crystallography, and cryo-EM. This project will deliver the first complete biochemical and structural mechanism of τm5U34 synthesis, explaining how its disruption is linked to pathologies, and open new avenues for therapeutic strategies against rare mitochondrial disorders.
Funding category: Financement public/privé
ANR JCJC MITOMOD 2026
PHD title: Biochemistry
PHD Country: France
Requirements
Specific Requirements
We are seeking a highly motivated candidate with a strong interest in structural biology, mechanistic enzymology, and RNA biology. Applicants should hold a Master's degree or equivalent in biochemistry, structural biology, or a related field. The successful candidate should demonstrate strong analytical skills, the ability to work both independently and as part of a multidisciplinary team, and excellent communication skills in English. Previous experience with manipulation under anaerobic conditions in a glovebox is a plus. Selection will be based on scientific excellence, motivation, and potential, without discrimination.
