Author Archives: Jerome Sohier

  • 0

Master 2 internship – 2019 – MOLECULAR MODELLING

This project will take place in a highly interdisciplinary environment at IBCP, in the group of Luca Monticelli (molecular modeling) and in close collaboration with Sofia Caridade who develops layer-by-layer (LbL) assemblies for drug delivery and other biomedical applications.

The ideal candidate has a solid background in physical chemistry. Numerical competences (e.g., experience in programming and computer simulations) are a plus, but they are not a requirement.

To apply, please send a CV and a motivation letter by e-mail to the two coordinators.


Molecular Microbiology and Structural Biochemistry (UMR 5086)

Luca Monticelli

Team: Modeling Biological Macromolecules (MOBI)

Luca.monticelli@ibcp.fr

Logo LBTI

Laboratory of Tissue Biology and Therapeutical Engineering (UMR 5305)

Sofia Caridade

Team: Colloidal Vectors and Tissue Transport

Sofia.caridade@ibcp.fr

 

Understanding the polymer behaviour in Layer-by-Layer assemblies

The alternating dipping of a charged surface into a polyanion and then into a polycation solution usually leads to the progressive formation of films on a solid support, defined as polyelectrolyte multilayers [Decher 1997]. This electrostatic self-assembly method is called Layer-by-Layer (LbL) deposition technique and has been developed as a way for producing organic and hybrid organic-inorganic supramolecular assemblies without requiring extensive equipment. In particular, in the biomedical field, these multilayers constitute versatile tools for the design of thin films or thick membranes containing macromolecules such as proteins, nucleic acids, or polypeptides with targeted properties [Monge 2015]. However, explaining the behaviour of the polymers in the LbL assembly remains a challenge due to major difficulties in structural characterization of the materials. Understanding the molecular origin of the mechanical properties of the film and deciphering the interactions with the biomolecules they contain would lead to a greater control of the bioactivity of the final medical device.

Here we propose to characterize the self-assembly, the mechanical properties, and the interactions of LbL multilayers using molecular simulations. During the past decades, molecular simulations have become a powerful tool for interpreting experimental results in terms of nanometre-scale structures and interactions, particularly for biological systems such as proteins, nucleic acids, carbohydrates, and lipid membranes. In the first phase of the project we will build molecular models for two charged polysaccharides, chitosan and hyaluronic acid, experimentally used in LbL systems for drug delivery. We will start by building all-atom models, with the highest level of accuracy. These will be used as a basis for the parameterization of coarse-grained models, featuring higher computational efficiency, which is essential to reach the large time and length scales needed to characterize the properties of polyelectrolytes. Coarse-grained simulations will allow the characterization of dynamic and elastic properties of the polymers in solution, and will be carried out with the MARTINI model, one the most widely used coarse-grained models. MARTINI has successfully been used for the description of a wide variety of biological and synthetic systems, including liposomes, models of complex biological membranes, polymers, and nanoparticles [Marrink 2007; Monticelli 2008; Marrink 2013]. Simulations will be validated by comparison with experimental data whenever possible.

Once the models of each polyelectrolyte will be built and characterized, in the second phase of the project we will perform self-assembly simulations, exposing a charged, solid surface alternatively to solutions of each polyelectrolyte – mimicking the experimental layer-by-layer deposition process. This will allow characterization of the multi-layer assembly in terms of internal structure (e.g., density profiles), dynamics (self-diffusion of the polymers), and elastic properties (e.g., Young modulus). Simulations of material swelling with aqueous solutions will also be possible, allowing changes in material properties and structural rearrangements upon modifications of pH and ionic strength, as well as exposition to other materials – allowing predictions on the interaction between LbL multilayers and proteins or particles. Such predictions will be used, in turn, to guide the experimental design of novel LbL materials with improved properties.

  • Decher G. Fuzzy Nanoassemblies: Toward Layered Polymeric Multicomposites. Science, 1997. 277(5330): p. 1232.
  • Monge C, et al. Spatio-Temporal Control of LbL Films for Biomedical Applications: From 2D to 3D. Adv Healthc Mater, 2015. 4(6): p. 811-30.
  • Marrink, SJ et al., The MARTINI Force Field: Coarse Grained Model for Biomolecular Simulations. J Phys Chem B 2007, 111, 7812-7824.
  • Monticelli, L et al., The MARTINI Coarse-Grained Force Field: Extension to Proteins, J Chem Theory Comput, 2008, 4, 819–834.
  • Marrink, SJ et al., Perspective on the MARTINI model, Chem Soc Rev, 42, 6801-6822.

  • -

Master Internship offer 2018

Research project title:

Role of α10β1 integrin in chondrocyte mechanotransduction 

Internship supervisor and Host laboratory:

Host laboratory: Laboratoire de biologie Tissulaire et Ingénierie thérapeutique (LBTI – CNRS UMR 5305)

Group : « Biologie et Ingénierie du Cartilage »

Team leader: Dr Frédéric Mallein-Gerin

Internship tutor: Dr Emeline Perrier-Groult (Chargé de Recherche CNRS, emeline.groult@ibcp.fr, Tél: 04 72 72 26 17)

Project description:

Context:

Although osteoarthritis (OA) can be initiated by multiple factors at multiple sites, mechanical overloading remains a key feature of OA pathogenesis. OA may result from excessively aberrant or physiologically normal mechanical stresses on initially healthy or pathologically-impaired articular cartilage, bone and ligaments. There is thus a need to decipher the mechanotransduction pathways involved in these tissues since alterations in these pathways likely increase the risk of OA. Our project focuses on the mechanotransduction in cartilage. Chondrocytes exposed to mechanical forces transmit the signals via various mechanotransducers including stretch-activated ion channels, receptor tyrosine kinases, the hyaluronan receptor CD44 and integrins. Integrins are transmembrane proteins consisting of α and β subunits and almost all cartilage proteins bind to integrins. Chondrocytes primarily use β1 integrins for adhesion to the cartilage matrix but the participation of the individual β1 integrin heterodimers in articular cartilage mechanotransduction is not clearly defined. While most literature data propose the fibronectin receptor α5β1 integrin as a critical mechanotransducer, the role of the prominent collagen-binding integrins such as a10β1 is unknown. The prominent expression of α10β1 integrin in articular chondrocytes and the partially overlapping chondrodysplasia phenotype of Itga10 null mice and mice with cartilage-specific deletion of Itgb1 makes us think that α10β1 is an integrin heterodimer which plays pivotal roles for functional and mechanical integrity of the joint tissue.

Internship project:

Our specific objective is to determine the role of α10β1 in chondrocytes mechanotransduction. We will use a cell system consisting of wild-type or Itga10 null chondrocytes embedded within agarose hydrogels and submitted to compression. We will investigate the impact of a10 privation on the phosphorylation state of signaling molecules and transcriptome. This project will bring new insight into how chondrocytes respond to mechanical forces, under the control of α10β1 integrin.

The ideal candidate has a solid background in cell and molecular biology. Competences in biochemistry and mechanobiology will be a plus but are not a requirement.

Lab publications:

  • Cueru L, Bougault C, Aszodi A, Berthier Y, Mallein-Gerin F, Sfarghiu AM. Mechanical and physicochemical responses for hyaline cartilage: role of protein β1 integrin in mechanotransduction. Comput Methods Biomech Biomed Engin. 2013;16 Suppl 1:330-1.
  • Bougault C, Cueru L, Bariller J, Malbouyres M, Paumier A, Aszodi A, Berthier Y, Mallein-Gerin F, Trunfio-Sfarghiu AM. Alteration of cartilage mechanical properties in absence of β1 integrins revealed by rheometry and FRAP analyses. J Biomech. 2013 Jun 21;46(10):1633-40.
  • Bougault C, Aubert-Foucher E, Paumier A, Perrier-Groult E, Huot L, Hot D, Duterque-Coquillaud M, Mallein-Gerin F. Dynamic compression of chondrocyte-agarose constructs reveals new candidate mechanosensitive genes. PLoS One. 2012;7(5):e36964.
  • Gouttenoire J, Bougault C, Aubert-Foucher E, Perrier E, Ronzière Mc, Sandell L, Lundgren-Akerlund E, Mallein-Gerin F. BMP-2 and TGF-beta1 differentially control expression of type II procollagen and alpha 10 and alpha 11 integrins in mouse chondrocytes. Eur J Cell Biol. 2010 Apr;89(4):307-14.
  • Bougault C, Paumier A, Aubert-Foucher E, Mallein-Gerin F. Investigating conversion of mechanical force into biochemical signaling in three-dimensional chondrocyte cultures. Nat Protoc. 2009;4(6):928-38.

  • 0

Master 2 in biomechanics

A master 2 student in biomechanics is sought to study the “Micro-mechanics of the vocal-fold tissue: experimental in situ mechanical tests using synchrotron imaging”.

The training period will take place in Grenoble (3SR Lab, CoMHet team).

The project  is linked with the LBTI through the MICROVOICE ANR

Master_internship_microvoice


  • 0

PhD Student on Marie-Curie grant

Adjuvatis cherche un PhD Student pour une bourse Marie-Curie dans le cadre de l’ITN DRIVE

Adjuvatis, as one of the 15 beneficiaries of the Marie Sklodowska-Curie Actions Innovative Training Network DRIVE (Driving next generation autophagy researchers towards translation), is hiring a PhD Student for 3 years starting from May 2018. We are looking for a motivated and enthusiastic Early-Stage-Researcher to join our team and to work on the Design and Evaluation of Therapeutic Biodegradable Particles Inducing Autophagy as Tumor Suppressor Tool.

For more information about Adjuvatis (new web site coming soon) and the project, please contact Charlotte.Primard@adjuvatis.com.

This project will be co-supervised by the team Vecteurs Colloidaux et Transport Tissulaire from the LBTI. Please have a look on the DRIVE project website for more information about the consortium and how to apply: https://drive-autophagy.eu/.

Consortium & Training: https://drive-autophagy.eu/

Research project (ESR14): 
https://drive-autophagy.eu/

Contact: charlotte.primard@adjuvatis.com

Co-supervision: http://lbti.ibcp.fr/?page_id=1722