دكتوراه بحثية مشتركة في جامعة Strasburg الفرنسية ومؤسسة Karlsruhe Institute of Technology الألمانية.

في حين إن أغلبنا يطمح إلى إنجازات علمية متفردة ويبحث عما يساعده في الوصول إلى غايته، تساهم المنح العلمية المقدمة من الحكومات أو المؤسسات غير الحكومية في بلوغ أهدافنا ولكن كثيراً ما نحتاج إلى دليل يرشدنا لنيل هذه المنحة أو تلك وانطلاقاً من إيمان (الباحثون السوريون) بشعارنا العلم هو الحل ننشر لكم مقعد دكتوراه بحثي في جامعة ستراسبورغ الفرنسية Strasburg ومؤسسة Karlsruhe Institute of Technology الألمانية وتهدف إلى دراسة تنظيم تجمعات CD44 / MET في غشاء البلازما باستخدام تقنيات المجهر المتقدم بإشراف البروفيسور Pr. Yves Mely في ستراسبورغ والبروفيسور Pr. Veronique Orian Rousseau في كارلسوه مدة ثلاث سنوات.

موعد انتهاء التقديم: 30 أيلول 2017

للتقديم إرسال السيرة الذاتية إلى:

yves.mely@unistra.fr

veronique.orian-rousseau@kit.edu

للمزيد من التفاصيل إليكم نص الإعلان:

French/German PhD position at the University of Strasbourg and Karlsruhe

Institute of Technology

Laboratoire de Biophotonique et Pharmacologie

(LBP) UMR 7213 CNRS

Faculté de Pharmacie

74 route du Rhin

F - 67401 Illkirch

هنا

Institute of Toxicology and Genetics

Karlsruhe Institute of Technology (KIT)

Postfach 3640

D-70621 Karlsruhe

هنا

Study of the organization and dynamics of CD44 / MET complexes at the plasma membrane

stimulated by endogenous (HGF) and bacterial ligands (Internalin B) by advanced microscopy

techniques

We are looking for a young scientist willing to work on an interdisciplinary project in cell biology

using advanced fluorescence microscopy techniques. The aim of this project is to characterize the

organization and dynamics of CD44 transmembrane glycoproteins that play an essential role in cell

migration and proliferation in physiological and pathological situations. The variety of CD44 functions

is related to their ability to associate with ligands such as MET (receptor tyrosine kinase (RTK)) and

HGF (human growth factor). Moreover, Listeria monocytogenes through its protein Internalin B (InlB)

uses also this MET pathway to infect host cells. As these processes take place at the plasma

membrane, the membrane organization plays a crucial role, in particular the lipid rafts, which are

small and dynamic membrane domains enriched with sphingolipids and cholesterol. The objective of

this PhD thesis will be to investigate the interplay between CD44v6, MET and the lipid domains on

HGF and InlB stimulation. The PhD student will first quantitatively characterize the interaction of

CD44v6 with MET promoted by HGF and InlB by FLIM-FRET in live HEK-293 cells. The amounts of

CD44v6/MET complexes and MET dimers will be determined in non-activated cells and compared to

those in the presence of HGF or InlB. Further information will be obtained by using downregulated

CD44v6 (siRNA and specific Crispr/cas constructs) and primary cells isolated from a Cd44v6 floxed

mouse. Quantitative data on MET dimerization in cells in which the expression of CD44v6 can be

manipulated will provide valuable insights into the role of CD44v6 in MET dimerization. In parallel,

deletion mutants of InlB will be used to analyze the contribution of the different InlB domains in the

recruitment of CD44v6. These investigations will be completed by solution measurements to

characterize the interaction of wild-type and mutant InlB with the purified CD44v6 ectodomain. The

comparison with HGF data will shed light on how L. monocytogenes takes advantage of the

MET/CD44v6 pair to interact with and then enter non phagocytic cells. In a second task, the phD

student will investigate by two-color super-resolution localization microscopy the role of lipid rafts in

the CD44v6/MET complex formation upon HGF and InlB activation. Localizations of membrane

proteins fused to photoactivable proteins or organic fluorescent dyes will be pinpointed and their

spatial distribution analyzed relative to those of lipid rafts. Treated cells with altered cell membrane

organization will also be measured. This will provide an extensive view of the distribution of CD44v6

or MET in and out of the raft domains. Complementary information in live cells will be obtained by

single particle tracking (sPT). This should help to further decipher the mechanism of CD44/MET

complex formation upon HGF- and InlB-activation. Taken together, these data will give a better

understanding of the interaction between CD44v6 and MET and its connection with the lipid

domains, as well as its stimulation by HGF and InlB. Comparison of HGF and InlB stimulations should

also give a clearer picture of how InlB hijacks the MET-related pathway to prompt bacterial invasion.

This project is funded for a 3 years PhD position by the French-German University and will be carried

out under the double supervision of Pr. Yves Mély (Strasbourg) and Pr. Veronique Orian-Rousseau

(Karlsruhe).

The student should have a background in biophysics with interest for biology or a background in

biology with interest for biophysical techniques. Excellent communication skills in spoken and

written English are expected.

Interested individuals should send a curriculum vitae, a motivation letter, and recommendation

letter(s) (or contact details of at least one referee) by e-mail to yves.mely@unistra.fr or

veronique.orian-rousseau@kit.edu.

Deadline for application : September 30, 2017