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Post-doc: Search for ligands of nuclear receptors involved in drug tolerance in nematodes

ABG-83272 Emploi Confirmé
28/02/2019 CDD 18 Mois > 25 et < 35 K€ brut annuel
INRA INTHERES
Toulouse - Occitanie - France
Biologie
  • Biochimie
  • Santé, médecine humaine, vétérinaire
Nuclear recepters, nematodes, C. elegans, Drug resistance, lipids.
Recherche et Développement

Employeur

The project is part of the research program of the INTHERES unit which concerns the study of the molecular mechanisms of resistance to antiparasitic drugs in target nematodes.

The unit belongs to both institutions ENVT and INRA Animal Health department, that have strong commitment to production animal health. ENVT works across disciplines and departments, fostering collaborative research, teaching and service. The laboratory has built an expertise in C. elegans culture and maintenance and has developed relevant drug analysis methods and approaches to explore drug efficacy, transport-mediated drug movements, and nuclear receptors activity. The research suroundings offer many types of platforms with large specificity and strong expertises. Institutional and international connections with parasitologists with expertise on pathogens facilitate the access to specific models and biological material required for the project.

 

We have identified important factors that control the efficacy of ivermectin, a widely used anthelmintic drug in veterinary and human medicine. Of most interest, inhibition of active drug transporters can significantly increase drug activity. More recently, the team has shown a nuclear hormone receptor regulating drug transporters, required for the model organism Caenorhabditis elegans to become resistant to ivermectin (see for review: Lespine et al, 2012; and relevant publications: Menez et al, 2012, 2016, 2019).

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Poste et missions

Overall purpose of the job: The project aims at studying the regulating cascade that controls the balance between drug efficacy and drug tolerance in C. elegans and in nematodes of clinical interest. The postdoc will work within a multidisciplinary research group to help develop and apply novel approaches to investigate the role of the drug-regulated events in sensitivity of parasites exposed to the different anthelmintic drugs. The project work will involve a mixture of cellular and worm biology, integrated in the context of adaption of organisms to drug exposure. The project will require genome analysis approaches, development of laboratory based molecular biology research, such as reporter gene technology and genome editing tools for precise genome modification, and imaging.

Mobilité géographique :

Internationale

Prise de fonction :

01/04/2019

Profil

Profile: We are looking for a PhD graduate in a relevant branch of natural science or a related field. The preferred candidate needs to be highly motivated, to enjoy cross-disciplinary work in an international environment, enthusiastic and good team player with excellent communication skills, with good command of English. A working knowledge of French would also be an advantage, but not essential.

Specific experience: A strong background in molecular biology and genetics, with experience in the field of mammalian nuclear receptors regulating gene transcription, are expected, with a mastery of the molecular tools necessary for these studies (bio-informatic tools for genome and protein analysis, molecular biology expertise for cloning plasmid construction and transfection in cells for gene reporter assay, transcriptomic analysis). A basic grounding on regulation of lipid metabolism are all considered assets. The balance of these different expertise will be considered on a case-by-case basis.

Objectifs

The primary objectives include the search for natural ligands for a nuclear receptor of interest and the identification of the regulated target genes, in nematode species of clinical interest. This will require genome analysis approaches, and development of laboratory based molecular biology research, such as reporter gene technology and genome editing tools for precise genome modification.The ligands are expected to be steroid like-molecules and lipid localisation and lipidomic approaches will be envisaged. The target genes will be identifyed by generating trangenic C. elegans expressing promoters-GFP constructs.

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