Description

Organisation/CompanyUniversité de RennesDepartmentISCRResearch FieldChemistry » Organic chemistryChemistry » Applied chemistryResearcher ProfileFirst Stage Researcher (R1)

Country

FranceApplication Deadline15 Dec 202- 23:
59 (Europe/Brussels)Type of ContractTemporaryJob StatusFull-timeHours Per Week40Offer Starting Date1 Feb 2024Is the job funded through the EU Research Framework Programme?Not funded by an EU programmeIs the Job related to staff position within a Research Infrastructure?No

Offer Description

Starting date:1st february 2024

Working hours :
Full time

Salary:
From €2097 gross/month (INM 426)

Level of education required:
Master or engineering degree in synthetic chemistry/medicinal chemistry
Project– Development of PROTACs for targeting IRE1 signaling using a targeted protein degradation strategy.
Disciplines– Medicinal chemistry / Chemical Biology / Synthetic chemistry

Context– IRE1 activation is a central element of the Unfolded Protein Response, an adaptative response consecutive to the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), a situation known as ER stress.

Cancer cells experience ER stress due to adverse environmental cues such as hypoxia or nutrient shortage and high metabolic/protein folding demand.

To cope with those stresses, cancer cells utilize IRE1 signaling as an adaptive mechanism, and as such, IRE1 plays a crucial role as a rheostat-like regulator of the cell fate controlling both survival and cell death.

The proof of concept of IRE1 inhibition as a new therapeutic modality has been demonstrated in various cancer models (1) ,however the current inhibitors present limitations hampering their clinical development (2) .

In this context, a targeted protein degradation (TPD) approach induced by PROteolysis Targeting Chimeras (PROTACs)(3)targeting IRE wouldi)artificially induce the degradation of IRE1, thereby neutralizing its catalytic and interactional functions (IPPs, scaffolding) andii)circumvent some of the limitations of known IRE1 inhibitors and lead to lasting control of the level of IRE1 activityin vivo.

A first generation of PROTACs inducing IRE1 degradation at nanomolar concentrations has been successfully developed, and the aim is now to their molecular structures by modulating both the ligand targeting IRE1 and the linker connecting it to the E3 ligand in order to improve their efficacy and physicochemical properties.

Working environment– This project is a collaboration between medicinal chemists (CNRS UMR 6226, COrInt team ) and biologists (Inserm U1242, PROSAC team ) and is taking place on the Villejean Health Campus of the University of Rennes.
Main activities–
• Plan and carry out syntheses, their follow up reactions and analyze compounds.
• Be proactive about possible improvements to synthesis routes and/or reaction conditions.
• Participate in scientific and technological monitoring in the fields explored.
• Complete laboratory notebooks according to internal guidelines.
• Write technical reports and complete compound identity sheets.
• Present progress and problems encountered at regular project team meetings.
• Participate in general laboratory tasks.
RequirementsResearch FieldChemistry » Organic chemistryEducation LevelMaster Degree or equivalent
Skills/Qualifications
Skills –
• Experience in organic synthesis and synthesis techniques required.
• Knowledge of purification methods (puriflash, HPLC) and analyses (NMR, LC-MS, FTIR).
• Proficiency in bibliographic research tools (SciFinder, PubMed), as well as molecular drawing software (ChemDraw).
• Knowledge of health and safety rules for chemical products handled.
• English (oral and written) - B2 level minimum.
• Ability to work as part of a team.
Specific Requirements

Profile– The candidate must have a Master of Science (MSc) or engineering degree with a background in medicinal chemistry or synthetic chemistry.
Previous experience in PROTACs and/or medicinal chemistry will be appreciated, but is not required. The candidate must demonstrate scientific rigor and a keen interest and motivation for interdisciplinary projects.
LanguagesENGLISHLevelGood
LanguagesFRENCHLevelBasic
Research FieldChemistry » Organic chemistryYears of Research ExperienceNone
Additional InformationSelection process
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