Medical University Graz (Doctoral School “Translational Molecular and Cellular Bioscience”; (http://www.medunigraz.at/16101) offers two positions each for the duration of three years to perform a doctoral thesis an the molecular and cellular (patho)physiology of G-protein activated inwardly rectifying potassium channel subunits in breast cancer cells (payment according to FWF (http://www.fwf.ac.at/de/projects/personalkostensaetze.html)).
While one PhD student (PhD#1) will mainly work on tasks 1+4 with electrophysiological techniques (Patch Clamp) and fluorescence microscopy, PhD#2 will work on tasks 2+3 with focus on biochemical and cell biology methods (see project description below).
Interested applicants holding a MSc, MD or equivalent degree are invited to submit their application containing a clear description of actual apprenticeship, research interests and motivation, together with the names of 2 referees to ao. Prof. Dr. W. Schreibmayer (Molecular Physiology Group, Institute of Biophysics, MUG; W.Schreibmayer@gmx.at) no later than February 15th, 2011. Specify PhD#1 or PhD#2.
G-Protein activated K+ channels (GIRKs) represent classical G-protein effectors mediating the regulation of excitability via hormones and neurotransmitters in electrically excitable tissue. Recent findings suggest that GIRKs are present in cancer cells contributing significantly to the malignancy of breast tumours. Despite of overwhelming evidence for their occurrence and a clear correlation with disease progression, insight into possible pathophysiological mechanisms, how GIRK proteins may promote cancer development does, at present, not exist. This proposal aims to test the crucial hypotheses that GIRKs promote cancer progression, either as the canonical and well known G-protein effectors, as G-protein independent K+ channels or via hitherto unidentified functions that are not related to K+ permeation at all. Experiments will be performed on non-tumourigenic, basal B-type, and malign, luminal type, tumour cells with different invasive potential.
The following specific goal!
s will be pursued:
1.: Identification of GIRK related K+ channels by electrophysiological characterizationof K+ channels (i) in benign and malign breast cancer cells, (ii) in cell lines overexpressing GIRK variants and isoforms and (iii) in cell lines where GIRK genes have been specifically silenced via siRNA.
2.: Characterization of GIRK variant/isoform protein and mRNA in breast cancer cells. Analysis of the effect of environmental factors that are relevant for tumour progression (mechanical stress; hypoxia) on expression levels.
3.: Analysis of simple vital cell functions that are important for tumorigenesis, such as proliferation, cell-adhesion and migration. The eventual role(s) of GIRKs variants/isoforms will be assessed by via specific overexpression/silencing.
4.: Characterization of the subcellular distribution of GIRK variants/isoforms in MCF10A and MCF7 cells under environmental factors, protein phosphorylation state and upon presence of signalling molecules in order to elucidate a possible role of GIRK trafficking in cancerogenesis.
Institute for Biophysics / Medical University Graz
Graz / Austria