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Reference : UMR7242-CORRIG-001
Workplace : ILLKIRCH,ILLKIRCH GRAFFENSTADEN
Date of publication : Monday, October 12, 2020
Type of Contract : FTC Scientist
Contract Period : 12 months
Expected date of employment : 4 January 2021
Proportion of work : Full time
Remuneration : between 2 675 and 3084 € gross monthly depending on experience
Desired level of education : PhD
Experience required : 1 to 4 years
Pseudomonas aeruginosa is considered by WHO to be a critical bacterium for decades to come. It is a widespread nosocomial pathogen that leads to serious infections in patients with cystic fibrosis or severe burns. This bacterium is naturally resistant to several families of antibiotics due to the low permeability of its outer membrane. In this context, the team develops new antibiotics whose structure allows them to cross the membrane to reach their target inside the cell. More specifically, the team uses siderophores (organic chelators produced and secreted by bacteria to assimilate iron) as vectors. Antibiotic-siderophore conjugates highjack the bacterial iron acquisition system to accumulate the antibiotic in the bacteria via a Trojan horse strategy. Some siderophore vector are difficult to synthesize by chemistry. For this reason, the new strategy developed in the lab is based on synthetic biology approaches and use bacteria to produce new siderophore vectors. In this context, the proposed mission aims to modify P. aeruginosa by metabolic engineering to produce large quantity of non-natural and functionalized siderophores. These newly synthesized siderophores will serve as precursors for the synthesis of innovative antitiobioc-siderophore conjugates.
The recruited researcher will conduct all the activities related to
- The design and the construction of P. aeruginosa mutants optimized for the production of the siderophore pyoverdine (the main siderophore produced by P. aeruginosa). A metabolic engineering strategy will be used to modify the regulation pathway of pyoverdine biosynthesis.
- The design and the construction of P. aeruginosa mutants capable of producing modified pyoverdine. Enzymatic engineering strategies will be conducted on the enzyme(s) involved in pyoverdine biosynthesis. The aim is to incorporate non-natural amino acids into the pyoverdine sequence.
- Production, purification and characterization of the modified pyoverdine
- Synthesis of new pyoverdine-antibiotic conjugates (by click chemistry) using the pyoverdine newly produced by the mutants and evaluation of their antimicrobial activity.
The recruited doctor must possess strong skills in molecular biology, microbiology and biochemistry. Ideally, the researcher should already have experience in metabolic or enzymatic engineering. Experience in using genome modification techniques, especially in Pseudomonas aeruginosa will be an asset. The recruited researcher must demonstrate autonomy and rigor and must be able to work in conjunction with the chemists of the lab. Fluency in French and English is required (read, written, spoken).
The recruited person will work in the Biotechnology and Cell Signaling laboratory (UMR7242 CNRS/University of Strasbourg). Le laboratory is attached to the Ecole Supérieur de Biotechnologie de Strasbourg (ESBS). The researcher will be part of the team « Metals and Microoganisms: Biology, Chemistry and Applications” codirected by I. Schalk and G. Mislin. The team is internationally recognized for its work on the elucidation of molecular mechanisms involved in iron homeostasis in pathogenic bacteria. The team develops axes of research on the validation of iron acquisition systems as therapeutic targets. The teams gathers biologists and chemists and use an interdisciplinary approach combining biochemistry, molecular biology, microbiology, synthetic biology and medical chemistry. Within this team, the research will work under the supervision of the project coordinator, Dr Coraline Rigouin.
The contrat is for 12 months, is renewable. It is financed by the ANR (ANR Jeune chercheur/jeune chercheuse PYANO).
the application file must contain a CV, a cover letter as well as names and emails of two references
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