Research

Analyzing & perturbing pathological protein functions

We are investigating the functional role of oncoproteins and tumor-suppressors such as transcription factors, kinases and phosphatases in normal cell growth and in tumorigenesis:

Hartl: The involvement of the transcription factor complex AP-1 (JUN/FOS) in cancerogenesis is studied. Hereby we focus on AP-1 affected gene expression in unique cancer cell models. Furthermore, synergistic oncogene functions in metazoan development are investigated.

Schneider: We analyze and perturb activities and interactions of the PP2A-specific ubiquitin ligase MID1 in tumorigenesis (MYC) and aging (FOXO3A).

Stefan: We analyze central protein kinases such as RAF, MEK and PKA. We develop strategies to identify compartmentalized substrates for kinase phosphorylation and their mode of molecular interactions to elucidate their roles in normal or malignant cell growth. Further, we search for pharmacological means to perturb defined protein complexes involved in aberrant signalling.

Emeritus / Bister: Molecular cancer research including analyses of oncogenes and proto-oncogenes such as MYC or RAF, and strategies for interference with oncogene function.

 

Systematic quantifications of molecular interactions & modifications

We analyze molecular interactions which are relevant for physiological and pathological cellular communication. Cancer or neurodegenerative diseases can be thought of as pathological alterations of molecular interactions:

Schneider: We study structure/function relationships of proteins and their pharmaceutical modulation with emphasis on components of the human ubiquitin system and its implications in human diseases like prostate cancer, movement disorders, and on embryonic malformations like the Opitz-Syndrome. In addition the role of the E3 ubiquitin ligase MID1, mTOR and PP2A in the regulation of specific local mRNA translation and its implications in intellectual disability syndromes are studied.

Stefan: We are interested in the in-depth analyses of compartmentalized receptor-effector pathways (GPCR, RTK). Besides analysing binary complex formation of central signalling proteins (kinase, scaffolds), systems-biology-based strategies are applied to obtain a more complete understanding how deregulated receptor activities affect intracellular effector pathways and protein-protein interaction (PPI) networks in the diseased cell setting (colon cancer, glioblastoma). Functional links of macromolecular kinase complexes to receptor pathways which enhance cancer cell-proliferation and are linked to neurodegenerative diseases are tested.

 

Cell-based Biotechnology

We apply unique biotechnological approaches to study defined molecular interactions in distinct cellular settings and for novel expression/selection systems for downstream processing in the bacterial cell system:

Schneider: Within the Austrian Center for Industrial Biotechnology (ACIB) we are engaged in the development and optimization of biotechnological methods, mainly novel expression/selection systems (patents) and tools for downstream processing. Also we are keen on reprogramming proteases to generate novel tools for establishing a generally and pharmaceutically relevant protein expression system for proteins and peptides in E. coli (US 8202696, No.20120208233, No.20120184624, US 2014/0170702, US20140170701A1).

Stefan: We develop unique reporter platforms for both, newly identified or recently established molecular interactions emanating from kinases (PKA, RAF) and/or oncoproteins (RAS, MYC). The goal is to adapt the reporter system for drug discovery efforts with the aim to accelerate the determination of drug efficacies and to determine OFF-target effects of lead molecules, peptides and approved drugs (PCT/EP2012/074489; EP16191530.1, EP16165865.3).