Is the Job related to staff position within a Research Infrastructure?: No
Offer Description
Mitochondria are central to ATP production, especially in energy-demanding heart and brain tissues. Defects in mitochondrial translation, often caused by missing post-transcriptional modifications of mitochondrial tRNAs, are a major cause of severe diseases. Among these, the C5-taurinomethylation of uridine 34 (τm5U34), catalyzed by the GTPBP3-MTO1complex, is essential for translation fidelity and respiratory chain function. Clinical mutations in genes encoding this complex cause the 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.
Where to apply
E-mail: antoine.gedeon@sorbonne-universite.fr
Requirements
Research Field: Chemistry » Biochemistry
Education Level: Master Degree or equivalent
Skills/Qualifications
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 of all backgrounds and are committed to ensuring an inclusive and supportive research environment. 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.
Research Field: Chemistry » Biochemistry
Additional Information
Selection process
Applicants should submit to Antoine Gedeon (antoine.gedeon@sorbonne-universite.fr) the following documents :
- A detailed CV
- A cover letter describing their motivation for the project and their research interests
- Academic transcripts for Bachelor's and Master's degrees (or equivalent)
- At least one letter of recommendation from an academic referee
Shortlisted candidates will be invited for an interview, during which they will have the opportunity to discuss their scientific interests and motivation for pursuing a Ph.D. Applications will be reviewed on a rolling basis until the position is filled.
Work Location(s)
Number of offers available: 1
Company/Institute: Sorbonne Université
Country: France
Contact
City: Paris
Website: https://www.sorbonne-universite.fr
Street: 4 place Jussieu
