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 anti-angiogenic drugs.

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)

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.

Prof. Dr. Walter Nickel
walter.nickel@bzh.uni-heidelberg.de
Heidelberg University Biochemistry Center
Heidelberg, Germany