A PhD position in the field of vascular oxidative stress
1) Project
This PhD project aims to study the role of the Aquaporin 1 (AQP1) in the vascular oxidative stress.
AQP1 is a water channel but we identified also as a "peroxyporin" with a role as a facilitator of the transmembrane passage of H2O2, in different cell types of the cardiovascularsystem including endothelial cells. We have already discovered that genetic deletion of AQP1 or its pharmacological blockade prevents cardiac hypertrophythrough a (ROS)-dependent intracellular signalling. Preliminary data suggest that these same interventions reduce vascular oxidative stress. Endothelial dysfunction, induced by such redox imbalance, is the prelude to CV diseases such as hypertension, metabolic syndrome and obesity, ultimately leading to heart attack. Therefore, these promising results warrant further understanding of the specific role of AQP1 in vascular homeostasis.
The project will include surgery on mice, classical molecular biology techniques (RNA extraction, RTqPCR and Western blot), primary culture of isolated vascular cells as well as exploration of vascular relaxation on myograph. This projectwill mainly include the comparison of phenotypic comparison of Aqp1 KO mice versus their wild-type littermates.
We will first characterize the expression of aqua(peroxy)porins in different types of resident (peri)vascular cells and then examine the paracrine effect of all residents (peri)vascular cell lines. We will pursue our experimentation by exploring the specific role of AQP1 in ROS-dependent vascular relaxation in open-ring aortas and mesenteric vessels mounted on Mulvany devices. Finally, we will explore the effect of AQP1 inhibition on endothelial dysfunction in WT mice treated with an AQP1 inhibitor.
2) Scientific environment
This project will take place at the Pole of Pharmacology and Therapeutics (FATH) of the Institute of Experimental and clinical research (IREC) of UCLouvain, Brussels (Head ofFATH: Professor Jean-Luc Balligand)
FATH has all facilities for cell cultures, biochemistry,molecular biology and access to a dedicated animal facility. In particular, FATH has access to the IREC institutional microscopy platform fully equipped with confocal and fluorescence microscopes and Mirax for highly efficient morphometric analysis of tissue sections. FATH acquired a Bruker EMX-micro spectrometer for EPR combined with spin trapping to measure NO and O2.
3) Skills/Qualifications
We are looking for someone who holds a Master in medicine, pharmacology, biomedical sciences or related disciplines. The candidate will have a good capacity for integration in an existing team and for collaborative work and the capacity to work independently. Most of all, the candidate will have a strong motivation, enthusiasm, perseverance, integrity and organization.
4) Eligibility criteria
- Hold a Master degree in a discipline of Sciences
- Be able to communicate orally and by writing in English and, ideally, in French
- Propensity to collaborative work, information sharing and interest in new technologies
- Be prepared to work with rodents
5) How to apply?
Sens your CV, a motivation letter and the contact details to Virginie Montiel
6) More info
Please contact Virginie Montiel (Virginie Montiel or +32 2 764 60 59)
Documentation related to the project:
- Inhibition of aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide. Sci Transl Med. 2020 Oct 7 ; 12(564). Montiel V, Bella R, Michel LYM, Esfahani H, De Mulder D, Robinson EL, Deglasse JP, Tiburcy M, Chow PH, Jonas JC, Gilon P, Steinhorn B, Michel T, Beauloye C, Bertrand L, Farah C, Dei Zotti F, Debaix H, Bouzin C, Brusa D, Horman S, Vanoverschelde JL, Bergmann O, Gilis D, Rooman M, Ghigo A, Geninatti-Crich S, Yool A, Zimmermann WH, Roderick HL, Devuyst O, Balligand JL
- Genetic deletion of aquaporin-1 results in microcardia and low blood pressure in mouse with intact nitric oxide-dependent relaxation, but enhanced prostanoids-dependent relaxation. Montiel V, Leon Gomez E, BouzinC, Esfahani H, Romero Perez M, Lobysheva I, DevuystO, Dessy C, Balligand JL. Pflugers Arch. 2014 Feb;466(2):237-51