Description du sujet de thèse

Regulation of Amylopectin Storage in the Apicomplexan Parasite Toxoplasma gondii
The PSB-Toxo project (ANR 2025) aims to dissect a novel regulatory pathway controlling amylopectin storage in the parasite Toxoplasma gondii.
T. gondii is a unicellular eukaryotic pathogen responsible for toxoplasmosis. It belongs to the Apicomplexa phylum, which includes some of the deadliest pathogens of medical and veterinary importance.

Chronic toxoplasmosis results from the establishment of the parasite's cyst form (bradyzoites) in specific tissues, primarily the brain and muscles. The formation of bradyzoite cysts in neurons or muscle cells is particularly relevant to human pathology, as reactivation of these cysts can lead to the deadly form of the disease, cerebral toxoplasmosis. It is also crucial for transmission, as cysts in muscle tissue are infectious to humans through the consumption of undercooked meat. Hence, bradyzoite cyst formation is a key factor in human and intermediate host pathogenesis.

Bradyzoites divide slowly and remodel their metabolic pathways to produce amylopectin granules that are essential for long-term survival in hostile environments. Amylopectin levels are tightly regulated, as both excess and deficiency are highly detrimental to cyst formation. However, the precise mechanisms regulating amylopectin levels remain unknown.

This project builds on recent findings by both partners of this ANR project (Dr. Gissot, CIIL, and Dr. Dauvillée, UGSF), who identified an enzyme with dual trehalose-6-phosphate synthase/phosphatase (TPSP) activity. Inactivation of this enzyme results in massive amylopectin accumulation in tachyzoites (https://doi.org/10.1371/journal.pbio.3002791).

The recruited candidate will be responsible for:

1. Producing and purifying recombinant TPSP and its individual catalytic modules.
2. Performing enzymatic characterization of these recombinant proteins.
3. Optimizing a high-sensitivity quantitative assay for trehalose and trehalose-6-phosphate in Toxoplasma extracts.
4. Quantifying and characterizing amylopectin in genetically modified parasites to study the enzyme's role in vivo.

This project is based on robust preliminary data and available materials from both collaborating laboratories. Our team has recognized expertise in glycobiology and will benefit from the full infrastructure of UGSF. Completion of the project within three years is fully anticipated.

The PhD student (M/F) will receive close supervision at the beginning of the project, progressing toward full autonomy. They will be enrolled in the Lille Graduate School of Biology and Health and will be scientifically supervised by Dr. Dauvillée (UGSF).

We are seeking a curious, motivated, and meticulous candidate (M/F) with a Master's degree (or equivalent) in biological sciences and a strong background in biochemistry. Interest or experience in enzymology and/or parasitology would be a significant asset.

Contexte de travail

The research will take place within the BIG team (Biological Interactions of Glycans) at UGSF (CNRS UMR 8576, University of Lille), in close collaboration with Dr. Gissot's team at CIIL (Inserm U1019; CNRS UMR9017; University of Lille, Institut Pasteur de Lille, Lille University Hospital), as part of the PSB-Toxo ANR project.
The PhD student (M/F) will benefit from tailored supervision, opportunities to develop new technical and analytical skills, and support to expand their scientific network and strengthen their publication record.

Contraintes et risques

Possible travel for conferences or collaborations.
Standard laboratory-related risks include exposure to chemicals, biological agents, temperature variations, and extended screen time.