PHD SCHOLARSHIP: Implications of charges in lipid membrane curvature induced by β-Arrestins
Department of Basic Sciences and Environment, Faculty of Life Sciences at University of Copenhagen is offering a PhD scholarship commencing 15 January 2012 or soon thereafter. The application deadline is 31 December 2011.
PROJECT DESCRIPTION
The PhD project is within the area of membrane biophysical chemistry studying different binding mechanisms into the cell. The membrane spanning G-protein coupling receptors (GPCR) facilitate crucial physiological responses to a variety of extracellular ligands such as hormones neurotransmitters, ions, photons and other stimuli, thus 50% of drugs available in the market today target GPCR. The biological mechanism behind the signaling is believed to involve several other biomolecules. For instance, b-Arrestins are proteins thought to turn off receptor signaling by assisting the recruitment of Clathrin leading to endocytosis of GPCRs, where the receptor is removed from the plasma membrane and the activating extracellular ligand. b-Arrestin was found to bind onto membranes containing phosphatidylinositol trisphosphate, PI(3,4,5)P3-lipids. We have recently shown that such binding is lipid specific and not driven by for instance the lipid charge. These experiments revealed a novel function of b-Arrestin that maybe critically contributing in the endocutosis of GPCRs.
Here we propose to characterize the interaction of b-Arrestin with lipid membranes using a combination of powerful and complementary biophysical characterization techniques. Using neutron scattering and reflectometry we will characterize the molecular structure of lipid membranes upon b-Arrestin binding to lipid membranes containing PI(3,5,5)P3-lipids. Using fluorescence microscopy we will characterize the kinetics and association energy of the protein with membranes of different composition and curvature. Using Atomic force microscopy and cryo-TEM we will characterize the lateral packing arrangement of the protein. Understanding how b-Arrestins interact with membranes is expected to reveal a bilayer-mediated contribution to the endocytosis of GPCRs.
The project involves collaboration with research partners at U.C. including Professors D. Stamou, M. Cárdenas, and Kell Mortensen, and Prof. R. Sunahara at University of Michigan.
Principal supervisor:
Professor Kell Mortensen
Department of Basic Sciences and Environment, University of Copenhagen
E-mail: kell@life.ku.dk
Co-supervisors:
Associate Prof. Marité Cárdenas Gómez
Department of Chemistry, University of Copenhagen
E-mail: cardenas@nano.ku.dk
Prof. Dimitrios Stamou
Department of Neuroscience and Pharmacology, University of Copenhagen
E-mail: stamou@nano.ku.dk
JOB DESCRIPTION
Your key tasks as a PhD fellow at LIFE are:
Manage and carry through your research project
Take PhD courses
Write scientific articles and your PhD thesis
Participate in international congresses
Stay at a research institution abroad for a few months
Teach and disseminate your research
QUALIFICATIONS
We seek a talented and dedicated student with
A Masters degree of relevance to the project (chemistry, biochemistry, biophysics, biology or similar)
The candidate should further have some experience/in depth knowledge in at least one of the techniques below:
Scattering techniques
Surface sensitive techniques
Biomembranes
FORMAL REQUIREMENTS
The successful applicant of the PhD scholarship must pass an enrolment in the LIFE Graduate School before the Faculty can finish the letter of employment.
Graduate School of Faculty of Life Sciences, LIFE strives to give our students the best international career prospects within our main research areas.
TERMS OF EMPLOYMENT
The position will be filled according to the agreement between the Danish Ministry of Finance and the Danish Confederation of Professional Associations. The post is covered by the Protocol on Job Structure.
APPLICATION PROCEDURE
Apply by clicking "Apply online" below.
Applications - in English - must include:
· Cover Letter, stating which PhD project you are applying for and detailing your motivation and background for applying for the specific PhD project.
· CV
· Diploma and transcripts of records
· Other information for consideration, e.g. list of publications (if any), peer reviewed and other
· Personal Recommendations
A maximum of 3 relevant scientific works which the applicant wishes to be included in the assessment.
The applicant will be assessed according to the Ministry of Science Technology and Innovation Executive Order no 284 of 25. April 2008.
By the end of January 2012, all applicants will have received information regarding the evaluation of their application. Receipt of the application will not be acknowledged.
The application must be received no later than 31 December 2011. Applications received later than this date will not be considered.
Questions
For specific information about the PhD scolarship, please contact
Prof. Kell Mortensen (kell@life.ku.dk );
Associate Prof. Marité Cárdenas Gómez (cardenas@nano.ku.dk ) or
Prof. Dimitrios Stamou (stamou@nano.ku.dk ).
General information about PhD programmes is available at www.LIFE.ku.dk/LIFEphd .
Deadline: 31-12-2011
FOR DETAILS, PLEASE REFER http://www.ku.dk/english/available_positions/vip/
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