PhD position in the Laboratory of Biomolecules (UPMC, Paris)

A PhD position (starting October 1st, 2015) is available in the NMR team of the Laboratory of Biomolecules, University Pierre and Marie Curie, Paris. The team (Structure and Dynamics of Biomolecules), headed by Prof. G. Bodenhausen, is located at University Pierre and Marie Curie and Ecole Normale Supérieure, in the center of Paris. The laboratory is equipped with 4 NMR spectrometers (400, 500, 600 and 800 MHz) and has dedicated equipment for protein biochemistry and biophysics (fluorescence, microcalorimetry…).

The PhD project, under the supervision of Prof. Olivier Lequin, aims to characterize the molecular interactions of Engrailed homeoprotein involved in Parkinson’s disease.

The candidate should ideally have some experience in protein NMR spectroscopy and protein biochemistry.

Applications should be sent to olivier.lequin@upmc.fr by May 26, 2015. Candidates must provide a full CV, a cover letter and a reference letter.

Homeoproteins form a widespread class of transcription factors that have master roles in the embryonic development of animals and which are linked to numerous physiological and pathological processes [1]. Within this family, Engrailed protein plays key roles in brain development and in the physiology of dopaminergic neurons. Engrailed administration in animal models of Parkinson’s disease increases the survival of dopaminergic neurons, which makes it a potential pharmaceutical protein [2]. Engrailed protein interacts with many partners (DNA, proteins, membranes) and regulates both transcription and translation. It is also involved in original cell signalling pathways implying direct translocation through biological membranes [3]. The research project developed in the laboratory aims to characterize at the molecular level the interactions of Engrailed involved in these different functions [4,5]. The PhD project will use NMR spectroscopy in combination with biochemistry (recombinant production of labelled proteins, site directed mutagenesis), biophysics (fluorescence, calorimetry) and molecular modelling.

References:

1. McGrath S.E., Michael A., Pandha H., Morgan R. Engrailed homeobox transcription factors as potential markers and targets in cancer. FEBS Lett. 2013, 587:549-554.

2. Alvarez-Fischer D., Fuchs J., Castagner F., Stettler O., Massiani-Beaudoin O., Moya K.L., Bouillot C., Oertel W.H., Lombès A., Faigle W., Joshi R.L., Hartmann A., Prochiantz A. Engrailed protects mouse midbrain dopaminergic neurons agains mitochondrial complex I insults, Nat. Neurosci. 2011; 14:1260-1266.

3. Prochiantz A., Fuchs J., Di Nardo A.A. Postnatal signalling with homeoprotein transcription factors. Phil. Trans. R. Soc. B 2014; 369:20130518.

4. Carlier L., Balayssac S., Cantrelle F.X., Khemtémourian L., Chassaing G., Joliot A., Lequin O. Investigation of homeodomain membrane translocation properties: insights from the structure determination of Engrailed-2 homeodomain in aqueous and membrane-mimetic environments. Biophys. J. 2013; 105:667-678.

5. Augustyniak R., Balayssac S., Ferrage F., Bodenhausen G., Lequin O. 1H, 13C, and 15N resonance assignment of a 114-residue fragment of Engrailed 2 homeoprotein, a partially disordered protein. Biomol. NMR Assign. 2011; 5(2):229-231.