Replication organelles (ROs) are novel membrane rearrangements formed in the host cell cytosol during infections of positive-sense RNA (+RNA) viruses, which are utilised as platforms for viral... Show moreReplication organelles (ROs) are novel membrane rearrangements formed in the host cell cytosol during infections of positive-sense RNA (+RNA) viruses, which are utilised as platforms for viral replication. This thesis addresses several open questions regarding the ROs of picornaviruses, including the host factor requirements for enterovirus RO formation, their potential functions, and the on-going uncertainty surrounding their origin. It extends our detailed understanding of enterovirus ROs to a second picornavirus genus, the cardioviruses, with broader ramifications for the development of antiviral strategies. The resulting data highlight an unexpected degree of flexibility in the use of membranes for vRNA synthesis, asking for a re-examination of how we define the replication organelles of +RNA viruses. Show less
Koning, R.I.; Faas, F.G.; Boonekamp, M.; Visser, B. de; Janse, J.; Wiegant, J.C.; ... ; Koster, A.J. 2014
Tumor cell migration and invasion are essential steps in cancer metastasis. Better understanding of the molecular mechanisms and function of the individual proteins affecting this behaviour is... Show moreTumor cell migration and invasion are essential steps in cancer metastasis. Better understanding of the molecular mechanisms and function of the individual proteins affecting this behaviour is essential to define potential novel drug targets to combat cancer. In general, cells in a normal tissue environment are attached to the extra-cellular matrix (ECM) and to each others. The interactions with the ECM are mediated through integrin adhesion receptors. Matrix adhesions are the physical link between the ECM and the actin cytoskeleton and are important for survival, proliferation, differentiation and migration. These cytoplasmic structures are composed of various signaling (phosphatases and kinases) and structural proteins that form the so-called __integrin-adhesome__. The spatial and temporal regulations of these components determine the type of matrix adhesion, their behaviour and finally the fate of the cell. For instance, resting cells such as renal epithelial cells show enlarged and stable focal adhesions as well as tight cell-cell contacts. In contrast, tumor cells which are able to invade and metastasize, lose their interactions with adjacent cells and show fast, small and highly dynamic matrix adhesions. In this thesis, we set up technologies and investigated the molecular mechanisms of the matrix adhesions dynamics in relation to tumor cell behaviour both in vitro and in vivo situation. Show less
