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Team Biology of Metals

Published on 25 January 2018



Team leader

 
Isabelle Michaud-Soret
Laboratoire Chimie et Biologie des Métaux
CEA-Grenoble
17 avenue des Martyrs
38 054 Grenoble cedex 09
Phone: (33) 4 38 78 99 40

Secretary:
Phone: (33) 4 38 78 40 95
Fax: (33) 4 38 78 54 87

Team members

Permanent scientists:
Mohamed Benharouga (Associate professor UGA)
Alexandre Bouron (CNRS researcher)
Patrice Catty (CEA researcher, LCBM Assistant Director)
Peggy Charbonnier (CEA technician)
Mireille Chevallet (CEA engineer)
Martine Cuillel (Inserm researcher)
Aurélien Deniaud (Associate professor UGA)
Laurence Macari (CNRS technician)
Isabelle Michaud-Soret (CNRS researcher, team leader)
Élisabeth Mintz (CEA researcher, gestion LCBM)
Roger Miras (CEA technician)
Julien Pérard (CNRS engineer)

Temporary scientists:
Julia Achard (Master I)
Aynur Ahamadova (post-doctoral fellow may 2013 -)
Mathilde Aubry (Master I)
Marina Bert (Master II)
Sylvain Chauvet (post-doctoral fellow)
Thomas Gallon (engineer april 2014 -)
Amal Kouadri (PhD student oct 2014-)
Chloé Leprêtre (L3 Pro)
Mohamed Ould Abeih (post-doctoral fellow april 2013 -)
Emeline Saudron (co-directed thesis with PCV)
Sophie Terrone (Master I)
Khémary Um (technician february 2014 -)
Giulia Véronesi (researcher avril 2014-)
Isabelle Worms (post-doctoral fellow)



Picture legend, from left to right:
back: Mohamed Ould Abeih, Julien Pérard, Laurence Macari, Mireille Chevallet, Sophie Terrone, Elisabeth Mintz, Roger Miras, Peggy Charbonnier, Mohamed Benharouga, Isabelle Michaud-Soret, Patrice Catty, Mathilde Aubry,
front: Marina Bert, Khémary Um, Aynur Ahmadova, Chloé Leprêtre, Martine Cuillel, Julia Achard,
insert: Alexandre Bouron, Aurélien Deniaud, Giulia Véronesi, Isabelle Worms, Thomas Gallon, Sylvain Chauvet, Amal Kouadri.

Former temporary scientists (2011-2013)
Addis Abébé: M2 2013
Geoffrey Bailleul : professional license course 1st semester 2011
Aurélie Biurrarena: M1 2011
Sylvain Chauvet: Thesis 2012
Cheickna Cissé: Thesis 2012
Flora Clément: M1 2012
Mariam El Khatib: M1 and M2 2012-2013
Caroline Fauquant-Pecqueur: researcher march 2011 - septembre 2012
Sandra Galop: Thesis 2012
Julien Gibon: Thesis 2011
Amélie Harel: professional license course 1st semestre 2012 then technician
Elaine Hilario de Souza: Thesis (Brazil may 2012 - march 2013)
Louis Jarvis: stage USA 2013
Anzéliha Kurt: M1 2013
Bénédicte Lafumat: M1 2012
Clément Levin: M1 2011
Sophie Mathieu: postdoctoral fellow 2011 - march 2013
Anne-Noëlle Petit: postdoctoral fellow july 2010 - decembre 2010
Camille Sageot: engineer course 2013
Wael Traboulsi: M1 2012


Presentation

The "Biology of Metals" or BioMet team focuses on the molecular and cellular mechanisms responsible for intracellular traffic, storage and regulation of various metal ions; the group studies the homeostasis of some essential metals such as copper, iron and zinc in prokaryotic and eukaryotic cells.

Our work is devoted to the study of detoxification and homeostasis of cadmium, calcium, copper, iron, zinc, cobalt and nickel metal ions in the cell. While cadmium is purely toxic, other elements are essential to cellular functions. However essential metal may, in case of deficiency or excess, compromise cell survival. Metallic cations are bound to a set of biomolecules that control their detection, transport, bioavailability and, possibly, their intracellular storage. The cellular homeostasis of these metals is finely regulated at the level of gene expression and protein synthesis.



The BioMet team studies several proteins which bind metallic cations and transfer them (i.e. exchange the metallic cations) to specific metalloproteins, some of them are able to interact with DNA or RNA to control gene expression or protein synthesis.

Within this framework, we focus on several membrane proteins whose function is to transport copper ions for one, chloride ions for another, and whose dysfunctionings are responsible for serious diseases in humans, such as Wilson's disease and cystic fibrosis. Our work focuses also on other membrane proteins responsible for transporting metals (TRP channels as TPRC6 and TRPM7 and P-type ATPases). Another concern of ours is the regulation of metal homeostasis by bacterial transcriptional regulators and eukaryotic translational regulators involved in the homeostatic control of iron and nickel. Studies of these regulatory systems, especially in stress conditions (metallic, oxidative or, for example associated with exposure to nanoparticles or other chemical molecules) is of particular interest to understand the metabolic disturbances caused.

Our research topics concern mainly fundamental research to better understand the mechanisms that regulate the intracellular concentration of the mentioned metals and the intracellular localization of membrane transporters. This is essential to understanding at the cellular and molecular level various pathologies related to dysregulation of metal homeostasis. Our work can also serve to identify new targets to fight the virulence of pathogenic bacteria. However, some research topics concern more finalized aspects as the search for antibacterial agents targeting the main regulator of iron homeostasis, the study of chelators for the removal of copper accumulation in the liver, the effect of an antidepressant on the brain zinc homeostasis or the toxicology of metallic nanoparticles.

Our axes of research aim to understand:

• the mechanism of heavy metal transport (Cd2+, Co2+, Cu+) through P1-ATPases and other efflux pumps
• the Cu+ delivery to the secretory pathway and the elimination of the excesses of Cu+ with the help of specific intracellular chelators
• the intracellular trafficking of transmembrane carriers - addressing, localization changes, degradation (human genetic diseases : Wilson's disease and cystic fibrosis)
l• the mechanisms of cross-regulatory network of Fur and NikR proteins, bacterial transcriptional metalloregulators and their involvement in the virulence of pathogenic bacteria (search of anti-Fur inhibitors with antibacterial aim)
• the transmembrane transport and storage of zinc ions in neurons, especially the involvement of cation channels such as TRPC6 channels in the transport of zinc
• the disruption of iron homeostasis and metal homeostasis and consequences in eukaryotes
• the interferences between metallic nanoparticles and metal homeostasis (LCBM transversal project involving several groups).


Keywords


Metal - cells - homeostasis - detoxification - membranes - transporters - intracellular traffic - degradation - proteins - binding sites - metalloregulator - bioinorganic - regulation of expression - coordination - ionic selectivity - Wilson's disease - cystic fibrosis - TRP channels.

Techniques

Molecular biology - site directed mutagenesis - heterologous expression in various systems (bacteria, yeast, insect and mammal cells) - primary or not cell cultures - purification of proteins - biochemistry - protein chemistry - light scattering - labelling - absorption spectroscopies, fluorescence, circular dichroism - enzymology - metabolic radiolabelling (pulse chase) - cellular imagery - electrophysiology.

Collaborations

- local: CEA-iRTSV, CEA-INAC, CEA-IBS, ESRF, EFS, CHU-DBI, CHU-Pneumology, IAB, GIN, UJF-DCM, UJF-DPM

- national: ENS (Lyon), INSERM-UMR-S 757 (Orsay), CNRS UMR 7178 (Strasbourg), Institut du thorax (Nantes), CEA-iBiTec-S (Saclay), CEA-iBEB (Cadarache), CEA-iRCM (Fontenay)

- international: 15 in Europe (5 Deutschland, 2 Greece, 1 Italy, 1 Norway, 2 Portugal, 2 Switzerland, 2 United-Kingdom), 5 in America (1 Brazil, 2 Canada, 2 USA), 1 in Asia (Japan)