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Reference : UMR5235-SEBBES-001
Workplace : MONTPELLIER
Date of publication : Tuesday, June 23, 2020
Scientific Responsible name : Sébastien Besteiro
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2020
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
Toxoplasma gondii is a ubiquitous protozoan parasite, with almost 30% of the world's population infected. It is the agent responsible for toxoplasmosis, a particularly serious disease when it is contracted by immunocompromised individuals, or by a developing fetus when the mother is infected during pregnancy.
Acute infection is associated with the rapid replication and the spread of tachyzoite forms of the parasite within the body. This phase of infection is often easily contained by the immune system. However, during the chronic phase of the disease, some parasites differentiate into slow-growing bradyzoite forms, establishing themselves in tissue cysts, mainly in the central nervous system and muscles. Bradyzoites persist for life in their host and can reactivate into tachyzoites in the event of immunosuppression. Importantly, this form of the parasite is resistant to all therapeutic approaches currently available.
T. gondii contains a plastid originating from a secondary endosymbiosis, called the apicoplast. It is a non-photosynthetic plastid but is essential for the survival of the parasite because it contains several important metabolic pathways. As such, it is a privileged target for the search for new therapeutic avenues.
Our objectives for this project are:
1) use innovative approaches to generate conditional mutants impacted for apicoplast homeostasis in the bradyzoite stage
2) to develop new cellular models allowing the differentiation of bradyzoites in vitro
3) to evaluate the contribution of the apicoplast to the metabolism and survival of bradyzoites, both in vivo and in vitro with the new tools developed
This project will involve the use a wide range of techniques in imaging, molecular and genetic biology (CRISPR / Cas9), cell culture and biochemistry.
Our team is located on the campus of the Faculty of Science of the University of Montpellier. It belongs to a multi-thematic research unit in which microbiology is very well represented. We have access to a number of shared equipment (microscopes, culture rooms, ...) and to technical platforms (imaging, proteomics, transcriptomics, etc ...).
Constraints and risks
Manipulation of a type 2 pathogen (Toxoplasma gondii).
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