Current Project(s) :

The major focus of my research is to reveal molecular mechanisms governing the secretion of diverse proteins. To address that, I exploit high-content high-throughput microscopy-based functional screening strategies (Starkuviene and Pepperkok, 2007, JBP, in press).

In the first instance, I have established a set of specific assays that enable to characterize quantitatively changes of the conventional secretory pathway induced by the over-expression of cDNAs tagged to GFP (Liebel et al., 2003, Starkuviene et al., 2004). As the next, I have been investigating whether trafficking of an alternative cargo, namely, collagen requires different molecular machinery than that of conventional secretory marker ts-O45-G (temperature sensitive mutant of vesicular stomatitis virus glycoprotein). By quantitative analysis of cellular effects under conditions of down-regulation by siRNAs, over-expression of cDNA-GFPs, as well as quantitative co-localisation experiments I could prove the presence of differential trafficking machinery for collagens (Starkuviene and Pepperkok, 2007, Traffic, in press). Hence, I am currently establishing a quantitative and versatile collagen secretion assay to re-constitute trafficking specificities of collagen and similar molecules in a high-throughput manner. That will enable a genome-wide comparison of molecular factors necessary for the secretion of ts-O45-G and collagen, and will hopefully lead to the identification of an evolutionary conserved minimal core transport machinery in mammalian cells from factors ensuring the specificity for different cargo.

Also, I am participating in the FP6-EU funded project TargetScreen: “Novel post-genomic cell-based screens for drug targeting in membrane protein disorders”. My main interest is to further develop microscopy-based assays to assess membrane trafficking of disease-related proteins under the conditions close to physiological ones in order to identify specific targets for drug development. For this purpose threes model proteins are chosen: CFTR – cystic fibrosis transmembrane conductance regulator as a representative of ABC transporters, MC4R – melanocortin receptor as a representative of G-protein coupled receptors, and EnaC - epithelial Na⁺ channel.