Ruprecht-Karls-Universität Heidelberg
HBIGS homepage | Forgot password
Lemberg0118 - Scientist (f/m) / PhD position
Project no:
Lemberg0118

Project leader:

Project supervisor:
Lemberg, Marius
Application deadline:
31. Mar 2019
Start of PhD project:
1. May 2019

Project description:

Title:
Function of the Presenilin-homologue SPP in regulation ER protein homeostasis
Summary:
The central question we are addressing is how membrane proteins that are either damaged or not needed by the cell are removed without affecting other proteins and the overall integrity of cellular organelles. Within this context, our main focus is to analyze how intramembrane proteases and their catalytically inactive homologues target selected membrane protein for degradation (see http://www.zmbh.uni-heidelberg.de/lemberg for more details). These central cellular homeostasis mechanisms have, when deregulated, been connected to neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. In this PhD project we aim to follow on our recent proteomics-based substrate identification and define the physiological function of the Presenilin-type intramembrane proteases SPP as a key regulator of ER function. Moreover, by using a combination of cell-free systems and tissue culture cells, we aim to decipher the molecular mechanism of how SPP is regulated.
References:
Yücel et al. (2019) The metastable XBP1u transmembrane domain defines determinants for intramembrane proteolysis by signal peptide peptidase. Cell Rep., in press (https://doi.org/10.1101/322107)

Avci et al. (2018) The intramembrane protease SPP impacts morphology of the Endoplasmic Reticulum by triggering degradation of morphogenic proteins. JBC, RA118.005642

Füller et al. (2018) CRISPR/Cas12a-assisted PCR tagging of mammalian genes. BioRxiv (https://doi.org/10.1101/473876)

Avci and Lemberg (2015) Clipping or Extracting: Two ways for membrane protein degradation. Trends Cell Biol. 25, 611-622.

Avci et al. (2014) The yeast ER-intramembrane protease Ypf1 refines nutrient sensing by regulating transporter abundance. Mol. Cell 56, 630-640.

Chen et al. (2014) Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u. EMBO J 33, 2492-2506.
Methods that will be used:
CRISPR/Cas-mediated gene editing, super-resolution microscopy, proteomics, lipidomics, cell biology, molecular biology, and membrane biochemistry.
Cooperation partners:
Britta Brügger (BZH), Michael Knop (ZMBH) ZMBH proteomics and imaging core facilities.
Personal qualifications:
We are looking for a highly motivated PhD student who hold a Master degree in biology or biochemistry. Expertise in membrane biochemistry and proteomics are of advantage.

The successful candidate will be part of a very collaborative reach team. Weekly progress reports, and journal clubs ensure a challenging, yet helpful environment, in which the candidates will broaden their theoretical and practical knowledge and independent investigative thinking skills. Our Institute offers an internationally competitive research environment with access to excellent facilities. Our staff is international and the working language is English.
Keywords:
Regulated intramembrane proteolysis, protein quality control, neurodegenerative disease.