Three-year PhD position in organic chemistry (funded by AMIDEX)

RESEARCHER PROFILE: PhD/ R1: First stage Researcher                  
RESEARCH FIELD(S)1: Chemistry
MAIN SUB RESEARCH FIELD OR DISCIPLINES1: Chemistry

JOB /OFFER DESCRIPTION 
The originality of this project lies in the development of a platform of stable prodrugs whose action is based on enzymatic activation. This project is in complete opposition with the current doxa used in pharmaceutical sciences. Indeed, the majority of approaches are based on the synthesis of molecules that inhibit an enzymatic activity, those leads to phenomena of resistance or unexpected adverse effects. Unfortunately, this methodology is powerless against the process of escape that generates this resistance.Our approach is based on the specific activity of proteases generated during pathologies on a prodrug attached to a peptide. After proteolysis, a labile alkoxyamine will be released and will spontaneously homolyze into two alkyl radical species one of them being very toxic. These radicals will react instantly and randomly on any nearby systems, avoiding any phenomenon of accustoming and resistance. It is important to note that this approach can be applied to most pathologies provided that a specific enzymatic activity is associated and that a toxic effect is needed.

Our project will make an important breakthrough in the concept of anti-cancer, antiparasitic, and antibacterial treatments through the development of a platform allowing controlled production of radicals whose targeting will be easily modified by changing the peptide vector at our convenience. The concept of this project has been validated by several encouraging biological preliminary results obtained on these different pathologies. These smart molecules will be hydrolysed in the presence of a protease specific to the tumor environment into another alkoxyamine R1R2NOR3.

This new activated alkoxyamine, obtained in situ, is highly labile and, consequently, homolyses spontaneously into a reactive species. The key-point of this work is to generate radical species at the right place and at the right time at physiological temperature.

In summary we propose to synthesize a prodrug bearing a peptide chain specifically activated to kill tumor cells. Furthermore, the activation of the prodrug will be monitored in vivo by imaging. So, we propose a new integrated theranostic approach of tumours. The applicant will oversee organic part of this project. Biological part will be performed at Bordeaux, Perpignan or Toulouse in collaboration with biologists specialized in cancer, in paludism and in bacteria disease.

This is an A*MIDEX funding with a gross salary 120 k€ (ca. 40 k€ per year for three years)

TYPE OF CONTRACT: PERMANENT: TEMPORARY / JOB STATUS: FULL TIME /HOURS PER WEEK: 35 hours
APPLICATION DEADLINE: 21 August 2024 & TIME 13:00
ENVISAGED STARTING DATE: 01/10/2024
ENVISAGED DURATION: 36 months
JOB NOT FUNDED THROUGH AN EU RESEARCH FRAMEWORK PROGRAMME

WORK LOCATION(S): 
Aix Marseille Université - UFR Science – Campus Scientifique de Saint-Jérôme - Institut de Chimie Radicalaire - Service 551-Team CRAB, 13397 Marseille Cedex 20, +33 631 210 576

WHAT WE OFFER: 
gross salary
120 k€ (ca. 40 k€ per year for three years); This job will offer skills in organic chemistry, radical chemistry and medicinal chemistry in innovative approaches

Additional information: The Euraxess Center of Aix-Marseille Université informs foreign visiting professors, researchers, postdoc and PhD candidates about the administrative steps to be undertaken prior to arrival at AMU and the various practical formalities to be completed once in France: visas and entry requirements, insurance, help finding accommodation, support in opening a bank account, etc. More information on AMU EURAXESS Portal 

QUALIFICATIONS, REQUIRED RESEARCH FIELDS, REQUIRED EDUCATION LEVEL, PROFESSIONAL SKILLS, OTHER RESEARCH REQUIREMENTS 
The candidate must be dynamic, motivated and enjoy working with team to successfully carry out this project. A strong background in organic synthesis is necessary. Experience in medicinal chemistry would be a plus but not required. The candidate must be capable of working in a team and communicating results during group seminars

Soft skills: This project request to work with different field chemistry, biology and analytic. 

REQUESTED DOCUMENTS OF APPLICATION, ELIGIBILITY CRITERIA, SELECTION PROCESS
A motivation letter, mark obtained in the master degree and a detailed CV with contact information for one or two references should be sent by e-mail. The candidate should have a goof level in Master 2 in Organic Chemistry or in engineer school, up to 12/20.

HOW TO APPLY
Prof. Gérard AUDRAN : g.audran@univ-amu.fr
Website: https://icr.univ-amu.fr/team/radical-chemistry-applied-to-biology/?ML=EN