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Emplois & formations

PhD position: Degradable Synthetic Antibacterial Copolymers for Therapeutic Applications, Marseille

Détails de l'offre

  • Type de poste: CDD, PhD/Doctorat
  • Secteur : Public
  • Localité : France 
  • Limite de candidature :
  • Profil de poste:
    Recherche et innovation
  • Domaine(s) :
    Autre

Description

Marseille – Provence-Alpes-Côte d’Azur – France
Degradable Synthetic Antibacterial Copolymers for Therapeutic Applications
Chimie

Description du sujet

State of art 

The rise of antibiotic resistance is probably one of the main actual and future public health challenges. Even if antibiotics have saved and still save millions of lives every year, all of them have been accompanied by the development of bacterial resistance few years after their introduction on the market. One explanation of the drug-resistance phenomenon comes from the action mechanism of antibiotics, which is based on their interaction with ADN, ARN, or enzyme of the bacteria.

After few contacts with antibiotics, bacteria are able to mutate or to inactivate the drugs and become drug-resistant or worse multi-drug resistant. « ESKAPE » pathogens exhibit a high level of antibiotic resistance and are today the main causes of nosocomial infections that lead to around 2 million of illness and 23,000 deaths.
Face to this warning situation, researchers try to find new antibiotics but the majority of the recent molecules proposed on the market like the new generation of β-lactamines do not present a higher efficiency and are based on the same action mechanism. It is therefore highly urgent to find alternatives to antibiotics.
Cationic synthetic amphiphilic antibacterial copolymers (sACs) appear as promising candidates with a high antibacterial activity associated with a low toxicity. Amphiphilic sACs contain cationic, hydrophobic, and hydrophilic groups and each of these components performs a specific function. Although the field of sACs is today highly dynamic (1,500 publications in 2020 with the keywords antibacterial polymer), their activity has been quite exclusively studied in vitro due to the non-degradability (C-C backbone) of the vast majority of the copolymers.

In the last two years, few publications reported very encouraging results on synthetic degradable cationic antimicrobial copolymers (i.e. copolymers with cleavable functions in the main chain) for in vivo applications. Nevertheless, mainly all of these synthetic degradable cationic antimicrobial copolymers are based on the same polycarbonate backbone, limiting the structural parameter that could be modified. Thus, to have more room for innovation in a such very important field, the preparation of other kinds of degradable sACs whose structural parameters could be deeply investigated will be highly desirable for developing/improving the use of sACs for in vivo application.Aim of the project

The objective of this work is to design and prepare a wide library of new synthetic degradable cationic antimicrobial copolymers by the combination of radical polymerization and radical Ring-Opening Polymerization (rROP) technique that our group (now worldwide recognized as one of the specialists) developed few years ago and that consists in developing comonomers to introduce hydrolysable moieties into the polymer backbone (Figuez 1).

Description du sujet

State of art 

The rise of antibiotic resistance is probably one of the main actual and future public health challenges. Even if antibiotics have saved and still save millions of lives every year, all of them have been accompanied by the development of bacterial resistance few years after their introduction on the market.

One explanation of the drug-resistance phenomenon comes from the action mechanism of antibiotics, which is based on their interaction with ADN, ARN, or enzyme of the bacteria. After few contacts with antibiotics, bacteria are able to mutate or to inactivate the drugs and become drug-resistant or worse multi-drug resistant. « ESKAPE » pathogens exhibit a high level of antibiotic resistance and are today the main causes of nosocomial infections that lead to around 2 million of illness and 23,000 deaths.
Face to this warning situation, researchers try to find new antibiotics but the majority of the recent molecules proposed on the market like the new generation of β-lactamines do not present a higher efficiency and are based on the same action mechanism. It is therefore highly urgent to find alternatives to antibiotics.
Cationic synthetic amphiphilic antibacterial copolymers (sACs) appear as promising candidates with a high antibacterial activity associated with a low toxicity. Amphiphilic sACs contain cationic, hydrophobic, and hydrophilic groups and each of these components performs a specific function. Although the field of sACs is today highly dynamic (1,500 publications in 2020 with the keywords antibacterial polymer), their activity has been quite exclusively studied in vitro due to the non-degradability (C-C backbone) of the vast majority of the copolymers. In the last two years, few publications reported very encouraging results on synthetic degradable cationic antimicrobial copolymers (i.e. copolymers with cleavable functions in the main chain) for in vivo applications.

Nevertheless, mainly all of these synthetic degradable cationic antimicrobial copolymers are based on the same polycarbonate backbone, limiting the structural parameter that could be modified. Thus, to have more room for innovation in a such very important field, the preparation of other kinds of degradable sACs whose structural parameters could be deeply investigated will be highly desirable for developing/improving the use of sACs for in vivo application.Aim of the project

The objective of this work is to design and prepare a wide library of new synthetic degradable cationic antimicrobial copolymers by the combination of radical polymerization and radical Ring-Opening Polymerization (rROP) technique that our group (now worldwide recognized as one of the specialists) developed few years ago and that consists in developing comonomers to introduce hydrolysable moieties into the polymer backbone (Figure 1).

Figure 1.Preparation of degradable antibacterial copolymers via the use of the radical ring-opening polymerization

The copolymerization of hydrophobic, cationic and cyclic monomers will allow to prepare such new antibacterial compounds. The (bio)degradability will be also investigated. These copolymers will be further be tested to find the more efficient antibacterial compounds with the minimal cytotoxicity.

The in vitro and ex vivo testing will be performed in Marseille (AMU, iSM2 and AMU, UMR_MD1 ). Finally, the best candidates will be tested in vivo in collaboration with the “Université de Nantes”.

Work of the PhD student: synthesis of the degradable antibacterial copolymers by radical ring-opening polymerization. Characterization of the copolymers and in particular by SEC and NMR. Study of the copolymers degradation by DLS, SEC or NMR.

Prise de fonction : 01/09/2021

Nature du financement : contrat doctoral

Précisions sur le financement : ANR

Présentation établissement et labo d’accueil

AIX-MARSEILLE UNIVERSITÉ

Institut de Chimie Radicalaire (UMR 7273, Aix-Marseille Université, Marseille, France) in the CROPS team (Chimie Radicalaire Organique et Polymères de Spécialité)

Site web : http://icr-amu.cnrs.fr

Intitulé du doctorat : Doctorat de chimie des polymères

Pays d’obtention du doctorat : France

Ecole doctorale : ED250

Profil du candidat

Engineer or master 2 student with a good knowledge in polymer synthesis and organic chemistry.

Pour postuler

Candidater sur le site de l’Association Bernard Gregory.