Author: Lubomir Vezenkov

GHSR-D2R heteromerization modulates dopamine signaling through an effect on G protein conformation

Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):4501-4506. doi: 10.1073/pnas.1712725115. Epub 2018 Apr 9

Damian M, Pons V, Renault P, M’Kadmi C, Delort B, Hartmann L, Kaya AI, Louet M, Gagne D, Ben Haj Salah K, Denoyelle S, Ferry G, Boutin JA, Wagner R, Fehrentz JA, Martinez J, Marie J, Floquet N, Galès C, Mary S, Hamm HE, Banères JL.

Abstract

IThe growth hormone secretagogue receptor (GHSR) and dopamine receptor (D2R) have been shown to oligomerize in hypothalamic neurons with a significant effect on dopamine signaling, but the molecular processes underlying this effect are still obscure. We used here the purified GHSR and D2R to establish that these two receptors assemble in a lipid environment as a tetrameric complex composed of two each of the receptors. This complex further recruits G proteins to give rise to an assembly with only two G protein trimers bound to a receptor tetramer. We further demonstrate that receptor heteromerization directly impacts on dopamine-mediated Gi protein activation by modulating the conformation of its α-subunit. Indeed, association to the purified GHSR:D2R heteromer triggers a different active conformation of Gαi that is linked to a higher rate of GTP binding and a faster dissociation from the heteromeric receptor. This is an additional mechanism to expand the repertoire of GPCR signaling modulation that could have implications for the control of dopamine signaling in normal and physiopathological conditions.

Cecile Echalier, presents her PhD work in SCF video

Cecile worked in the ibmm peptide team during her PhD (2013-2016), in collaboration with Prof. Ahmad Mehdi (ICGM). She worked on the development of hybrid hydrogels for 3D printing and tissue engineering.  Now postdoctoral researcher in Heidelberg, she speaks about her PhD in a video realized by Société Chimique de France (SCF). Cecile was distinguished as ‘woman in science’ 2016 by Unesco&L’Oréal  for her research work in chemistry.

 

ORALCANCERPRINT

ORALCANCERPRINT
Biofabrication of an oral squamous cell carcinoma model by 3D bioprinting

Funding : Emergence, Cancéropôle Grand Sud-Ouest

June 2018 – June 2019

 

Nowadays, treatments of oral squamous cell carcinoma is principally based on excision surgery and can be associated with radiotherapy and chemotherapy. It is really important to have a better understanding of the neoplastic oral mucous membrane to develop less aggressive treatment. This project is a multidisciplinary project aiming at designing an oral squamous cell carcinoma model by 3D bioprinting, to help the development of cancer treatments.

The aim of the project is to develop an in vitro 3D organotipic model of oral mucous membrane with the help of 3D-bioprinting of cellularized layers. The use of two different 3D bioprinting technologies will allow to reproduce the architecture of cancer tissues at a macroscopic and a microscopic scale. Layers of hybrid collagenous peptide based hydrogel encapsulating gingival fibroblasts will be 3D printed by extrusion with layers of endothelial cells in the same hydrogel but 3D printed by a laser-assisted technology, to create a vascularized tissue. Finally, a layer of cancerous keratinocytes embedded into the hydrogel, printed by laser, will cover the model. The complexity of the model will give a better understanding of cellular communication in oral cancer and will be a platform for drug screening.

 

This project is developed in collaboration with BioTis Team ( Dr. Adrien Naveau and Dr. Raphael Devillar), Inserm 1026 : Tissular Bio-engineering team, Bordeaux.

THE TEAM

Gilles Subra
raphael devillard
RAPHAEL DEVILLAR (BioTis)
adrien naveau
ADRIEN NAVEAU (BioTis)
Ahmad Mehdi
AHMAD MEHDI
Laurine Valot
LAURINE VALOT

A Review from the team just published in J Mater Chem B!!! Inorganic polymerization: an attractive route to biocompatible hybrid hydrogels

Congratulations for the first paper of Titouan!

J. Mater. Chem. B, 2018,6, 3434-3448,  doi 10.1039/C8TB00456K

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Titouan is the first author of a really nice, well illustrated and comprehensive review about hybrid hydrogels, (i.e. defined by the coexistence of organic and inorganic moieties in water). Inorganic polymerization, i.e. the sol–gel process, is one of the main techniques leading to hybrid hydrogels. In addition, the mild reaction conditions make this process very promising for the preparation of water-containing materials and their bio-applications.

Have a look at J Mater Chem B !

J. Mater. Chem. B, 2018,6, 3434-3448,  doi 10.1039/C8TB00456K

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Inorganic polymerization: an attractive route to biocompatible hybrid hydrogels

J. Mater. Chem. B, 2018,6, 3434-3448,  doi 10.1039/C8TB00456K

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Abstract

As an intermediate state between liquid and solid materials, hydrogels display unique properties, opening a wide scope of applications, especially in the biomedical field. Organic hydrogels are composed of an organic network cross-linked via chemical or physical reticulation nodes. In contrast, hybrid hydrogels are defined by the coexistence of organic and inorganic moieties in water. Inorganic polymerization, i.e. the sol–gel process, is one of the main techniques leading to hybrid hydrogels. The chemoselectivity of this method proceeds through hydrolysis and condensation reactions of metal oxide moieties. In addition, the mild reaction conditions make this process very promising for the preparation of water-containing materials and their bio-applications.

Can Heterocyclic γ-Peptides Provide Polyfunctional Platforms for Synthetic Glycocluster Construction?

Chemistry. 2018 May 30. doi: 10.1002/chem.201802032

Simon M, Ali LMA, El Cheikh K, Aguesseau J, Gary-Bobo M, Garcia M, Morère A, Maillard LT.

Abstract

Sugars play key roles in many molecular and cellular communication processes involving a family of proteins named lectins. The low affinity associated with sugar recognition is generally counterbalanced by the multivalent nature of the interaction. While many polyglycosylated architectures have been described, only a few studies focused on the impact of topology variations of the multivalent structures on the interaction with lectin proteins. One major interest of our group concerns the design of new highly predictable and stable molecular pseudo‐peptide architectures for therapeutic applications. In such a context, we described a class of constrained heterocyclic γ‐amino acids built around a thiazole ring, named ATCs. ATC oligomers are helical molecules resulting from the formation of a highly stable C9 hydrogen‐bonding pattern. Following our program, we herein address the potential of ATC oligomers as tunable scaffolds for the development of original multivalent glycoclusters.

Structure based drug design

Structure Based Drug Design

We develop several projects related to the characterization and inhibition of molecular interactions between proteins and protein-ligand.

Based on molecular modeling studies of protein-protein or protein-ligand interactions, our first step is to design pharmacophore constraints to orient the design of putative inhibitor candidates. In collaboration with chemists, the most suitable scaffold (foldamer, chemical molecule and peptide) is selected and candidates are synthetized. Then, after purification of functional proteins, we carry out protein-protein and protein-ligand interaction studies by biophysics to evaluate the inhibitory potency of compounds.

CONTACT

Alain Chavanieu
Alain Chavanieu
Ludovic Maillard
Ludovic Maillard
Sébastien Estran
Sébastien Estran