Détection de l'intensité lumineuse : puits d'électrons couplés à l'OCP et rapporteurs optiques.[...]

Organisation/Company Université Grenoble Alpes Research Field Biological sciences » Biology Researcher Profile Recognised Researcher (R2) Leading Researcher (R4) First Stage Researcher (R1) Established Researcher (R3) Application Deadline 8 Apr 2026 - 22:00 (UTC) Country France Type of Contract Temporary Job Status Full‑time Is the job funded through the EU Research Framework Programme? Not funded by a EU programme Is the Job related to staff position within a Research Infrastructure? No

Offer Description

Recent work of our lab (Munro et al., 2026, submitted) has resolved key atomic intermediates of orange carotenoid protein (OCP) photoactivation across sub‑ps to µs timescales using time‑resolved structural snapshots integrated with cryo‑EM, MD, spectroscopy, and mutagenesis. This mechanistic framework enables repurposing OCP (echinenone‑loaded) as a light‑intensity sensor and proximity actuator in engineered Escherichia coli.

This PhD will develop two OCP‑coupled systems:

• OCP state reporters. The PhD candidate will construct fluorescent protein–OCP assemblies to generate a light/intensity‑dependent optical readout (FRET and/or carotenoid‑mediated quenching). Starting from N‑ and C‑terminal fusions, he will optimise geometry and binding via AI‑driven protein design (e.g., BoltzGen) and verify whether energy transfer meliorates.
• OCP‑controlled electron sink. The PhD candidate will engineer a high‑flux, self‑contained O₂‑reduction module by splitting a multidomain flavodiiron protein (~843 aa) into an FDP catalytic core and an NROR/Rb reductase tail, tethered to the OCP N‑ and C‑terminal domains to couple electron transfer to OCP conformational switching. Function will be quantified in vitro by UV–Vis/fluorescence spectroscopy and NADH oxidation assays. Structural insights will be obtained by cryo‑EM and/or crystallography – if crystals are obtainable. In this context, our ongoing MIAI‑funded project aimed at developing AI‑driven protein crystal design could help.

Début de la thèse : 01/10/2026WEB : category: Contrat doctoralConcours pour contrat doctoral

We will seek to recruit a PhD candidate with a background and strong interest in structural biology, which will facilitate and speed‑up the required training. Her/his main task will consist of expressing protein, carrying out their characterisation by spectroscopy and determining their structure by crystallography and cryo‑EM. The candidate will be encouraged to develop skills with AI‑driven tools such as BoltGen. Since the OCP purification protocol and the crystallization conditions (both to form macrocrystals for conventional rotational crystallography and microcrystals for serial crystallography) are already known and used in our lab, the candidate should be able to proceed swiftly with the spectroscopic characterization and preparation experiments at the synchrotron or by cryo‑EM. The candidate will be encouraged to start with a literature study at the beginning of his/her PhD and to track relevant literature during the course of the project. This will not only facilitate correct decision‑making throughout the project, but also ease drafting articles and writing the dissertation. Finally, the student will write the results of his studies in research publications.