Ruprecht-Karls-Universität Heidelberg

Open Positions in the Seedorf Lab


PhD position at the Centre for Molecular Biologie (ZMBH), University of Heidelberg

The group of M. Seedorf at the ZMBH, University of Heidelberg has a strong interest in intracellular protein trafficking (1) and the organization and function of peripheral ER subdomains. We found that the integral membrane protein Ist2 employs a lipid-binding signal for sorting to the yeast cortical ER. This signal binds specific plasma membrane (PM) lipids and this interaction is sufficient for the sorting of membrane proteins to ER-PM contacts (2, 3). We would like to study this new mechanism in detail and learn about the physiological function and the molecular organisation of ER-PM contacts.

Project 1. Function and trafficking of chloride channels in yeast

Based on sequence similarity to calcium-activated chloride channels of the mammalian PM (TMEM16 family), we hypothesise that yeast Ist2 functions in a similar manner as ion channel. By phenotypic characterization of IST2 mutants, we would like to understand the function of Ist2 as ion channel, which is located at ER-PM contacts. How are these ER-PM contacts defined on the molecular level and do changes in the intracellular distribution of phosphoinositide lipids have an impact on the localization and function of Ist2? These questions will be addressed by using yeast genetics, fluorescence microscopy, in vitro lipid-binding assays, biochemistry with membrane proteins and biophysical methods to study interaction between amphipathic a-helices and membranes.
 

Project 2. Functional coupling of ER and plasma membrane

The sorting of yeast Ist2 and the recruitment of STIM proteins to peripheral ER utilizes similar mechanisms. STIM proteins, which exist in almost all mammalian cell types, function in calcium signalling (4). At low calcium concentration in the ER lumen, these type I membrane proteins move to the PM, where they bind and activate calcium channels and thereby evoke calcium influx. The C termini of yeast Ist2 and mammalian STIM proteins contain similar lipid-binding signals. By detailed analysis of these signals, we would like to understand how the recognition of specific lipids at the cytosolic face of the PM contributes to the sorting of membrane proteins to PM-associated ER subdomains. Than we would like to ask if such lipid-mediated sorting of membrane proteins is a general process and whether we do find such lipid-binding signals in other membrane proteins as well? For this project we employ bioinformatics, work with mammalian tissue culture cells, fluorescence microscopy, FRET, measurement of intracellular calcium concentration, in vitro lipid-binding assays and biochemistry with membrane proteins.

We are looking for highly motivated PhD students with a strong background in biochemistry, cell biology or molecular biology. Successful candidates will be part of a young and international, highly motivated team of PhD students that works at the forefront of scientific research. The new PhD students will be member of the Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS). Please apply directly at HBIGS (http://www.hbigs.uni-heidelberg.de/). For more information see http://www.zmbh.uni-heidelberg.de/seedorf/default.shtml or send email to m.seedorf@zmbh.uni-heidelberg.de
 

References:

(1) Nickel W. and M. Seedorf (2008). Unconventional mechanisms of protein transport to the cell surface of eukaryotic cells. Annu Rev Cell Dev Biol, 24:287-308.

(2) Maass, K., Fischer, M.A., Seiler, M., Temmerman, K., Nickel, W. and M. Seedorf (2009). A signal comprising a basic cluster and an amphipathic alpha-helix interacts with lipids and is required for the transport of Ist2 to the yeast cortical ER. Journal of Cell Sciences 122:625-635.

(3) Fischer MA, Temmerman K, Ercan E, Nickel W and M. Seedorf M (2009). Binding of Plasma Membrane Lipids Recruits the Yeast Integral Membrane Protein Ist2 to the Cortical ER. Traffic 10:1084-1097.

(4) Vig M and JP Kinet (2009). Calcium signaling in immune cells. Nat Immunol 10:21-27.


 
















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