Annonces
Postdoctoral Researcher
Synthesis of peptides for the evaluation of their self-assembly capacity
Project description
Organic nanotubes are promising nanomaterials displaying many applications in nanotechnology, in particular in nanomedicine. Peptide nanotubes are a class of organic nanotubes attracting immense interest due their wide range of bio- (and other) functionalities, which leads to many potential use in
nanotechnology and biomedicine. The supramolecular stacking of cyclic peptides is a versatile approach for the formation of nanotubes. Peptide nanotubes are generally very long (several micrometers) and their length is difficult to control. Up to now, one of the main limitations of most nanoparticles used in nanomedicine is their lack of size homogeneity, resulting in potential variability in terms of organ biodistribution, cellular internalization, elimination, and fate in vivo. Therefore, there is a strong need of synthesizing size-monodisperse short nanotubes that will certainly be excellent candidates for future clinical translation.
In this context, this project is centered on the synthesis of length-controlled polymer-peptide hybrid nanotubes as carriers for the delivery of an anticancer drug. For this purpose, biocompatible polymers will be conjugated to cyclic peptides and the self-assembly capacity of the polymer-peptide conjugates will be assessed. The presence of the polymer chains will put strain on the peptide core through steric repulsions, allowing to reduce the length of the nanotubes and enable their use as carriers of an anticancer drug.
The project is focused on 1) the synthesis of the cyclic peptides, 2) the conjugation of polymers, 3) the study of the self-assembly capacity of the polymer-cyclic peptides into nanotubes, 4) the loading of an anticancer drug in the nanotubes and 5) the evaluation of the pH-controlled release of the drug.
More detail here
Eligibility criteria
The candidate must have a PhD with a strong a background in organic synthesis, in particular peptide synthesis. Knowledge on supramolecular chemistry and cell biology would be appreciated. The candidate must be an independent, well-organized and rigorous person. He / she must have good interpersonal skills. He / she must manage his own research and coordinate the different aspects of the work to meet deadlines. He / she must provide ideas for new research projects, carry out scientific bibliography, compile results for publication in peer-reviewed journals and present the results orally.
He / she should actively participate in laboratory meetings.
Offre de financement de thèse
SUBJECT OF THE THESIS:
This thesis project is concerned with the simulation and molecular modeling of microbial glycolipid membranes and their association and solubilisation of membrane proteins. Glycolipids are abundant constituents of biological membranes, where they are known to be involved in lipid lateral phase separation resulting, for example, in a local enrichment of membrane-anchored proteins, preferential membrane budding or selective ion attractivity. In particular, we are interested in microbial glycolipids (MG), which are biodegradable, non-toxic, carbohydrate-rich biocompatible glycosylated amphiphiles (also known as biosurfactants). These types of lipids have not been well investigated either with an experimental or theoretical approach. In this thesis we plan to work in close coordination with experimental laboratories to investigate the structural and mechanistic properties of a few MG, such as their membrane interdigitated structure, the headgroup/hydrophobic thickness, the distribution homogeneity of glucose and carboxyl headgroups of the MGs and its alkyl chain conformations and hydration. To achieve that we plan to use commonly available molecular dynamics and modeling codes such as gromacs to be used at high performance computing facilities. The successful candidate for this fully funded studentship will have a background in biophysics and molecular modeling and will be familiar with common script languages such as Python.
Candidate background: Candidates who have completed a master 2 in biophysics/chemistry/physics. Knowledge of rudiments of a programming language and/or script are highly appreciated.
Location: I2BC, CEA-Saclay – Ile-de-France – France
Subject title: Modeling and simulation of microbial glycolipids and their interactions with membrane proteins
Scientific field: Informatic, Physic, Biochemistry
Keywords: Molecular modeling, simulation, molecular dynamics, membranes, amphiphiles, membrane proteins