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Doctoral position in Chemistry/Imaging

This offer is available in the following languages:
Français - Anglais

Date Limite Candidature : dimanche 22 mai 2022

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General information

Reference : UMR5536-ERITHI-001
Workplace : BORDEAUX
Date of publication : Sunday, May 1, 2022
Scientific Responsible name : Pr Eric Thiaudière / Pr Sylvain Marque
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

MOLECULAR IMAGING OF PROTEOLYSIS : SYNTHESIS OF BIS-RADICALS AND APPLICATION TO MRI OF INFLAMMATION
Context 
Personalized medicine needs new approaches of diagnosis aiming at deciphering molecular mechanisms inherent to the occurrence of diseases. In this frame inflammatory processes or some sort of cancers involve enzyme activity such as proteases that may be targeted for early diagnosis. Over more than one decade project partners have gained a lot of experience in developing new radical probes (nitroxides) that were specific to proteases. Such probes served as contrast agent for a quite original modality of Magnetic resonance Imaging at low field that relies upon the presence of free radicals which induce signal enhancement through the Overhauser effect. In this project it is proposed to evaluate new bis-nitroxide molecules in terms of enzyme specificity and their ability to unveil inflammation in rodents through the generation of MRI contrast.
Objectives and Thesis Outline
The goals of this thesis are the synthesis, physico-chemical and biochemical assessment and the evaluation of the biological response of new bis-radicals linked to a peptide motif in order to perform in vivo MRI of inflammation in rodents. The envisioned probes are either bis-nitroxides or nitroxide-iminoxyl that will be specific to neutrophil elastase or to metalloproteinase-12. T

Area of Research and Scientific themes

The project is at the crossroads of organic radical chemistry, physical chemistry (notably spin spectroscopy), enzymology and bioimaging. Owing the this multidisciplinary nature, the work shall be performed in two locations (Bordeaux and Marseille).

Programme

- Chemical synthesis (UMR 7273, Aix-Marseille) et purification
- EPR assessment (UMR 7273, Aix-Marseille)
- In vitro enzymatic assessement (UMR 5536, Bordeaux)
- Evaluation of potential diagnosis : in vivo MRI (UMR 5536, Bordeaux)

Work Context

Both teams are expert in their respective area of research : chemistry and physical chemistry of radical species (Marseilles) on one hand and biochemistry and MRI development (Bordeaux) on the other hand. Each team display human and material potential that are suitable for this kind of interfaced project.

Laboratory partnership

- The Magnetic Resonance Centre for Biological Systems, UMR5536, Bordeaux .

This laboratory was created in 1995. It houses ca. 50 people (researchers, engineers and technicians). The laboratory designs and uses new Magnetic resonance tools to investigate living organisms (in vivo MRI). Of note, a research group is involved in cutting-edge development of low field MRI .

- The Institute for Radical Chemistry, UMR 7273, Aix-Marseille
This laboratory gathers 120 people and is one of the french leader in the design of radical chemistry for a variety of applications. Leader. In particular the CRAB group (Radical Chemistry for Biology) produced a number of chemical probes that are used in a wide biological context.
Thesis supervisors:

- Pr Eric Thiaudière

Biochemist, physical-chemist, expert in MRI in vivo, especially at low field. He was involved in the supervision of 10+ PhD since 1996. Authors of 90+ international papers. Partner of 3 EU projects.

- Pr Sylvain Marque

Organic chemist expert in the design of radical probes and EPR assessment. Supervisor of 15+ PhD theses since 2000. Author of 200+ papers (h=35). Partner of many academic and industrial projects worldwide.

Doctoral schools
- Ecole Doctorale Sciences de la Vie et de la Santé (Life and Health, University of Bordeaux)
- Ecole Doctorale de Chimie (Chelistry, Aix-Marseille University)

The « Health and Life » Doctoral Shool in Bordeaux encompass all the biological domains, noticeably the speciality called « Bioimaging »

Constraints and risks

The work is expected to be performed in two locations : UMR 7273 (Marseilles) et UMR 5536 (Bordeaux). As such a number of travels are anticipated but the unity of places will be favored over significant time periods. The beginning of the work will take place in Marseilles.
A safe environment will be warranted according to the current rules. Each laboratory has a Health & safety department and a dedicated training course will be attended. No major safety issue is forcasted.

Additional Information

Student's skills

The applicant is graduated (MSc) or has an Engineer grade, preferably in Chemistry. Additional background in biology is strongly desired. The applicant should be familiar with with organic synthesis and physico-chemical assessment of molecules. Knowledge on spin spectroscopy are mandatory. Moreover, an open-minded behavior towards biochemistry is welcome.
The doctoral fellow shall be stand-alone in the scientific approach and should show actual abilities in oral and written expression, both in french and english. The PhD student we be asked to interact with any member of the laboratories, whatever their role in the current project.

Supporting documents
A detailed resume, a digital copy of the MSc or Engineer research report, a detailed report of the ratings and rankings for the years 3, 4 and 5 of the higher education syllabus, and two independent recommendation letters from persons with their contact information should be joined to the application folder.

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