PhD position funded by the FRM through the “Fondation Line POMARET-DELALANDE, thesis on rare diseases"

We are seeking for a higly motivated candidate to postulate for a PhD
position funded by the FRM through the "Fondation Line POMARET-DELALANDE,
thesis funding on rare diseases".

http://www.cbs.cnrs.fr/index.php/fr/208-fr/emplois2/602-phd-position-deciphering-mechanism-activity-of-potent-biased-agonists-active-in-nephrogenic-insipidus-disease

Thesis topic: Deciphering mechanism activity of potent biased agonists
active in nephrogenic insipidus disease.

G-protein Coupled Receptors (GPCRs) represent the largest class of
eukaryotic cell surface receptors involved in signal
transduction. The V2 vasopressin receptor (V2R) is a prototypal receptor
for peptides, which governs water homeostasis in the body. Mutations of
V2R are responsible for a rare genetic disease, the congenital Nephrogenic
Diabetes Insipidus (cNDI), characterized by excessive urine voiding,
dehydration, hypernatremia. We have characterized the very first biased
ligands of V2R that rescue with long lasting effects V2R mutants
responsible for NDI  (Jean-Alfonse et al., J Am Soc Nephr 2009; Rahmeh et
al., Proc Natl Acad Sci USA 2012).

The thesis aims at structurally
characterize  the mode of action of biased ligands versus non-biased
ligands using liquid NMR as principal tool (Sounier et al. 2015). The PhD
student will be  involved in the preparative biochemistry of V2R and NMR
experiments design, recording and analysis. The results that will be
generated from this work will pave the way to the design of more specific
V2R ligands targeting NDI with fewer side effects and longer efficacy.

The thesis work will be carried out in close collaboration between the two
groups involved: Hélène Déméné, Centre de Biochime Structurale and Bernard
Mouillac, Institut de Génomique Fonctionnelle, both in Montpellier (South
of France). Both groups develop transverse unique cutting-edge
methodologies (biophysics,
pharmacology, biochemistry, molecular simulations) to decipher the
structural bases of GPCR signaling.

Selection criteria: Master students with a background in structural
biology, especially in NMR, are encouraged to apply before July,12th 2018.
PLease contact Helene.demene@cb.cnrs.fr or bernard.mouillac@igf.cnrs.fr

The "Prix  de Thèse sur les Maladies Rares" funded by Fondation
Pomaret-Delalande-FRM is described here (dead line: August the 2nd, 2018)

https://www.frm.org/upload/pdf/espace-chercheur/ao_prix_pomaret2018.pdf
Net salary/month : 1400 euros, for three years.

Bibliography:
Sounier R, Mas C, Steyaert J, Laeremans T Manglik A, Huang W, Kobilka BK,
Déméné H*, Granier S (2015)(*co-corresp author) Nature 524(7565):375-8
285(9): 6337-4

Hélène Déméné, PhD
Centre de Biochimie Structurale
UMR 5048, INSERM 1054, Université de Montpellier
29, rue de Navacelles
34090 Montpellier Cedex
France
Tel: +33 (0) 4 67 41 77 01
Fax: +33 (0) 4 67 41 79 13
e-mail: Helene.Demene@cbs.cnrs.fr