| Research is aimed at analysis of regulation mechanisms of dynamic interactions between macromolecules that play a key role in physiological and pathophysiological processes and whether they are targets for therapeutic control. Research is organised in three lines: [1] Involvement of proteases in adhesion, deattachment and invasion of metastatic cancer cells. Colon cancer metastasis in rat liver is used as an in vivo model to study activation and activity of relevant proteases in the metastatic process. We want to localize quantitatively which proteases are actively involved in which stages of metastasis in living cells and tissues and how their activity can be manipulated. [2] Involvement of proteases in breakdown of extracellular matrix. Breakdown of extracellular matrix proteins is a highly regulated process that needs various proteases. It has been established by us that lysosomal proteases and matrix metalloproteases play a crucial role in this process in a tissue-dependent manner. At present, we are investigating the functional role of this heterogeneity. [3] Determination of dynamic processes in living cells and tissues. We have found that enzymes studied quantitatively show a highly dynamic behaviour in kinetic parameters in intact cells and tissues that allow rapid alterations in metabolism when necessary. Similarly, processes in the interphase nucleus are also highly dynamic. At present, we want to establish mechanisms that regulate these rapid changes in kinetic parameters of enzymes and translocation in the nucleus in living cells and tissues. |
