HBIGS
Universität Heidelberg
Project Title:
Molecular analysis of an autocrine secretion/signaling loop of the
proangiogenic growth factor FGF2
Project leader:
Prof. Dr. Walter Nickel, Heidelberg University Biochemistry Center
Application Deadline:
January 31, 2013
Start of PhD project:
March 1, 2013
Source of Funding:
DFG
Project Description:
Our laboratory investigates the unconventional secretory pathway by
which tumor cells release the proangiogenic growth factor FGF2, a potent
stimulator of tumor-induced angiogenesis. This process involves
phosphoinositide dependent oligomerization of FGF2 concomitant with the
formation of a lipidic membrane pore in the plasma membrane and is
regulated by tyrosine phosphorylation of FGF2 (see references below).
We have identified a pair of tightly related but distinct tumor cell lines that
differentially respond to extracellular FGF2 by either being stimulated or
being inhibited in cell proliferation and cell viability. Based on a complete
transcriptome analysis of these cell lines under various experimental
conditions and validation by RNAi screening, this project aims at
identifying new factors involved in FGF2 secretion and autocrine FGF2
signaling. A follow up analysis of selected gene products will aim at a
more detailed understanding of FGF2 secretion and autocrine signaling
and the identification of new targets for the developemnt of antiangiogenic drugs.
HBIGS
Universität Heidelberg
References:
Original articles:
Steringer et al. (2012) PI(4,5)P2 Dependent Oligomerization of Fibroblast
Growth Factor 2 (FGF2) Triggers the Formation of a Lipidic Membrane
Pore Implicated in Unconventional Secretion. J. Biol. Chem. 287:2765927669
Ebert et al. (2010) Tec kinase mediated phosphorylation of Fibroblast
Growth Factor 2 is essential for unconventional secretion. Traffic 11:813826
Torrado et al. (2009) An Intrinsic Quality Control Mechanism Ensures
Unconventional Secretion of Fibroblast Growth Factor 2 in a Folded
Conformation. J. Cell Sci. 122:3322-3329
Temmerman et al. (2008) A Direct Role for Phosphatidylinositol-4,5bisphosphate in Unconventional Secretion of Fibroblast Growth Factor 2.
Traffic 9:1204-1217
Zehe et al. (2006) Cell surface heparans sulfate proteoglycans are
essential components of the unconventional export machinery of FGF-2.
Proc. Natl. Acad. Sci. U.S.A. 103:15479-15484
Reviews:
Walter Nickel (2011) The Unconventional Secretory Machinery of
Fibroblast Growth Factor 2. Traffic 12:799-805
Walter Nickel and Catherine Rabouille (2009) Mechanisms of Regulated
Unconventional Protein Secretion. Nat. Rev. Mol. Cell Biol. 10:148-155
Methods that will be used:
- Complete transcriptome analysis including regulatory RNAs in
collaboration with Vladimir Benes (Genomics core facility at EMBL
Heidelberg).
- RNAi screening to validate gene products in collaboration with Rainer
Pepperkok (EMBL Heidelberg)
HBIGS
Universität Heidelberg
A functional analysis of selected gene products with potential roles in FGF2
secretion and autocrine signaling will involve a large range of methods in
biochemistry and molecular cell biology.
Collaboration Partners:
Vladimir Benes, Genomics Core Facility at EMBL Heidelberg
Rainer Pepperkok, EMBL Heidelberg
Profile of candidate’s qualification:
We are looking for enthusiastic and motivated students with a master
degree in the life sciences.
Please send this form to the HBIGS office by email to: r.lutz@hbigs.uni-heidelberg.de