Missions

A post-doctoral position (for 24 months) is currently available for a collaborative project (co-PIs: Dr. Laurent Yvan-Charvet, Nice and Dr. Florent Ginhoux, Villejuif), focusing on the role of macrophage Piezo1 in atherosclerosis. Candidates should have a keen interest in understanding immunology and associated disease states. A strong backround in cell biology, metabolism and mouse experimentation is required.

Activités

Atherosclerosis (AS) is a common chronic inflammatory vascular disease characterized by the formation of fatty plaques within the arterial wall that narrow the lumen, with a further risk of plaque rupture and thrombosis. Macrophages (Mo) contribute to the initiation and progression of AS by engulfing oxidized LDL (oxLDL), converting into foam cells and forming a fatty streak. Typically, plaques form at sites of disturbed blood flow, such as arterial curvatures and bifurcations. The mechanosensitive (MS) ion channel Piezo1 present in Mo is emerging as a novel important player in the etiology of AS. Our preliminary findings indicate that chronic oxLDL, as well as its major oxysterol 7-ketocholesterol (7-KC), cause a potentiation of Piezo1 to mechanical stimulation in both mouse Mo and transfected HEK cells. 7-KC induces an increase in Piezo1 current amplitude, as well as a slowing down of channel inactivation. In vivo, we analyzed the cellular composition of AS aortas from Western diet-fed hypercholesterolemic Ldlr-/- mice, which received WT or Piezo1 KO (Lysm Cre Piezo1del/fl TomatoSTOPfl) bone marrow transplants. While complete blood count was similar between both groups, the number of Tomato positive myeloid cells is reduced by about 50% in the aortas of mice complemented with KO transplants versus WT, with an even stronger reduction in the number of Mo. Moreover, atheromatous plaque formation is significantly reduced in the KO. Altogether, our initial findings indicate that Mo Piezo1 is up-modulated by pro-atherogenic lipids and plays an important role in AS progression. Our specific aims in this project are to: 1) investigate Piezo1 function in monocytes (Mono) and Mo foam cells; 2) decipher how Piezo1 influences Mono aortic infiltration and/or Mo egress; 3) explore the potential role of Piezo1 in aortic Mo differentiation; 4) target Mo Piezo1 in AS using a dietary strategy. Globally, we will provide novel knowledge concerning the role of Piezo1 in innate immunity and its implication in AS progression.

Compétences

1) Animal experimentation
2) Confocal microscopy
3) Immunology
4) Metabolism
5) Lipid biochemistry

Contexte de travail

Our laboratory is part of the CNRS Institute of Molecular and Cellular Pharmacology located in the City of Nice-Sophia Antipolis (South East of France). This is a leading centre in biology research with state of the art equipment. The city of Nice offers an international dynamic cultural experience combined with a magnificent scenery and easy access to air travel.

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.

Contraintes et risques

None

Informations complémentaires

Interested candidates should e-mail a letter of application, including a CV and the names and addresses of at least two referees to:
Eric HONORE (honore@ipmc.cnrs.fr)
IPMC-CNRS
Université Côte d'Azur
660, route des Lucioles
Sophia Antipolis
06560 Valbonne, France
Tel : 33/4/93/95/77/45
http://www.ipmc.cnrs.fr/?page=honore