PHD position: Deciphering mechanism activity of potent biased agonists active in nephrogenic insipidus disease
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".
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. The "Prix de Thèse sur les Maladies Rares" funded by Fondation Pomaret-Delalande-FRM is described here (dead line: August the 2nd, 2018)
Net salary/month : 1400 euros, for three years.
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): 6337-47.
Rahmeh R, Damian M, Cottet M, Orcel H, Mendre C, Durroux T, Sharma KS, Durand G, Pucci B, Trinquet E, Zwier JM, Deupi X, Bron P, Banères JL, Mouillac* B, Granier S (2012) (*co-corresp author) Proc Natl Acad Sci USA 109(17): 6733-38.
Jean-Alphonse F, Perkovska S, Frantz MC, Durroux T, Méjean C, Morin D, Loison S, Bonnet D, Hibert M, Mouillac B, Mendre C. (2009) J Am Soc Nephrol. 20(10):2190-203.
2 YEARS POSTDOCTORAL POSITION AT CENTER FOR STRUCTURAL BIOCHEMISTRY (CBS) IN MONTPELLIER, FRANCE
Structure and Dynamics of Membrane Assemblies Team
Biophysics and Bioengineering Department
SCIENTIFIC PROJECT AND JOB DESCRIPTION:
The project is focused on the development of a novel Atomic Force Microscope imaging mode based on tip-sample energy transfer at nanoscale to image living cells membranes with high spatial and temporal resolution.
The project is clearly at the frontier between Physics and Biology/Biochemistry. At first, the proposed development will permit the characterization of forces at nanoscale avoiding the use of linear/non-linear harmonic oscillators as in the case of AFM, SFA and optical tweezer. Indeed, short range interactions will be quantified by means of advanced single-molecule fluorescence techniques improving by orders of magnitude the force resolution of conventional AFM modes.
The PostDoc will work in close collaboration with Dr. Pierre-Emmanuel Milhiet and Dr. Emmanuel Margeat and is expected to build/develop this unique instrument participating in ongoing in-house R&D programs of the team, mainly focused on biological membranes remodeling projects. The position is supported by a CNRS MOMENTUM 2017 grant (http://www.cnrs.fr/fr/cnrsinfo/les-laureats-de-lappel-projets-cnrs-momentum).
CBS (http://www.cbs.cnrs.fr) is an Institute dedicated to research at the forefront of structural biology and biophysics. It also proposes facilities in these fields. Montpellier is a stunning city on the French Riviera with a significant international community. The research of our group is focused on the development and use of advanced microscopies (AFM and single molecule fluorescence microscopy) to decipher the molecular mechanisms associated to the organization and remodeling of
biological membranes. The group includes 10 people with 5 permanent researchers. The team has a longstanding record in the training of young apprentices and the activity of mentoring young people is part of the position.
More info on http://www.cbs.cnrs.fr/index.php/en/home-equipeb3
1. L. Costa et al. NanoLetters, 16 (9), 2016. - 2. B. Gumi-Audenis et al. Journal of Synchrotron Radiation, 22, 1364-1371, 2015. - 3. B. Gumi-Audenis et al. Nanoscale, 10(1), 2017. - 4. C. Chevalier et al. Nature Communication, 10765, 2016. - 5. P.E. Milhiet et al. PlosOne, 5(10), 2010.
Highly motivated and ambitious candidates are encouraged to apply. We require:
o Excellent teamwork skills.
o A PhD degree in physics, biophysics or related scientific disciplines.
o A high level of interest in instrumentation and in the development of non-conventional protocols and techniques.
o Relevant scientific experience supported by publication record.
o Excellent English communication skills.
Previous experience in Atomic Force Microscopy, Fluorescence imaging, Optics, Cell Culture, Electronics and Wet Lab experience as well as computational (i.e. Labview, Python, Matlab) skills will be positively considered.
TERMS OF SALARY AND EMPLOYMENT:
Successful applicants will receive a salary according to CNRS rules and experience starting from January, 1st 2019.
o Curriculum vitae with a list of publications, a report on previous research and the names, addresses and contact details of 2 referees.
o All relevant diplomas, including grades.
Deadline for application is October 15th, 2018. All applicants will be notified whether their application
has been selected for an interview (seminar + personal visit or skype chat).