This research and development project was funded under the call “Strengthening Research, Development and Innovation Capacities” (IRI) from the European Regional Development Fund.

This research and development project was funded under the call “Strengthening Research, Development and Innovation Capacities” (IRI) from the European Regional Development Fund.

The possibility of synthesis of reagents for sample preparation for MS analysis will be investigated, which would enable original "all-in-one" quantitative and qualitative analysis of proteins for the needs of industry and biomedical sciences.

The Hedgehog signaling pathway has been implicated in development of various tumors, but the exact roles and molecular mechanisms are still not understood. The focus of this research are the tumors harboring BRAF or NRAS mutations, and their differential response to Hedgehog pathway inhibition. Both BRAF and NRAS non-canonically activate the three GLI proteins, but the activity and interplay of this interaction is still unclear. With this project we propose to determine the exact transcriptional targets of GLI1, GLI2 and GLI3 proteins in melanoma with different genetic backgrounds, either harboring a BRAF mutation, a NRAS mutation, or no mutation in these two genes.

The main goal of this project is to investigate MSI and EMAST microsatellite instability in sporadic colon cancer and to correlate the obtained results with clinico-pathological characteristics of tumors and patients.

Recent failures of clinical trials against Alzheimer’s disease (AD) with γ-secretase inhibitors have shifted the focus to BACE1 as a key AD drug target. However, the complex phenotypes of BACE1-null mice and the numerous recently identified BACE1 substrates suggest that the inhibition of BACE1 may cause unacceptable side-effects. This emphasizes the need to investigate more thoroughly the mechanisms of action of this enzyme and the functions of its substrates. The goal of this project is to characterize the processing and distribution of the two top BACE1 substrates, seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L) in a transgenic (tg) mouse model of Alzheimer’s disease. In line with the recently identified accumulation of BACE1 in human and tg-mouse AD brains we propose that accumulation of BACE1 within presynaptic terminals and enhanced cleavage of its substrates at or near the synapse, in addition to APP, may add to synaptic (dys)function, learning and memory deficits, neurodegeneration and the pathogenesis of Alzheimer’s disease.