Ph.D. Fellowship (SSBCV) : FUNTIONAL CHARACTERISATION OF CYSTEINE CATHEPSINS IN THE APICOMPLEXAN PARASITE CRYPTOSPORIDIUM PARVUM

Cryptosporidium parvum, apicomplexan parasite , host-pathogen interactions, virulence factors, cysteine cathepsins

 

The candidate must be in the last year of its Master’s (or equivalent) degree, or already hold a Master’s degree (or equivalent), preferably in biology or microbiology.
We are looking for a curious and motivated student with strong critical thinking skills, enjoying teamwork but also capable to work in autonomy.
Past experience of internship in a research laboratory in the field of infectious diseases or parasitology would be appreciated. Technical skills involving cell culture (biosafety level 2 laboratory), molecular biology (RT-qPCR, cloning, transfection) and/or biochemistry (enzyme assay) would also be appreciated.
It is important to stress that the PhD project requires some animal experimentation.
The student must have very good written and oral communication skills in both French and English.

Niveau de français requis: Intermédiaire supérieur: Vous pouvez utiliser la langue de manière efficace et vous exprimer précisément.

Niveau d'anglais requis: Intermédiaire supérieur: Vous pouvez utiliser la langue de manière efficace et vous exprimer précisément.

 

Project description

Cryptosporidium parvum is an apicomplexan parasite responsible for cryptosporidiosis, a
zoonotic disease affecting both human and animal health. This diarrhoeal disease, and its
associated clinical symptoms, can be severe and lead to death in some cases, in particular in neonates and immunocompromised individuals. The authorised drugs that are currently used to treat cryptosporidiosis are not completely effective as they do not provide a total clearance of the parasite, and no vaccine is available. A better understanding of the biology of the parasite, and of the host-Cryptosporidium interactions, is crucial in order to identify new therapeutic targets and develop new control strategies.
Cysteine cathepsins are proteolytic enzymes that hydrolyse a peptide bond on a
substrate protein using the thiol group of a cysteine residue as a nucleophile. Cysteine
cathepsins expressed by different protozoan parasites have been shown to play key roles in their associated pathogenesis (e.g. invasion of host cells or tissues, hydrolysis of proteins from the host or from the parasite itself, modulation of the host immune response), making them attractive chemotherapeutic and vaccine targets.
The genome of C. parvum harbours five genes encoding putative cysteine cathepsins
(also named ‘cryptopains’), but these proteases have only been scarcely studied so far. This PhD project aims at describing the cathepsin activities that are expressed by C. parvum and functionally characterising their role(s) in the parasite’s life cycle by means of biochemical and molecular approaches. The expected results will expand our knowledge of the biology of C. parvum and identify new virulence factors in this parasite species.

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