Endocytosis is a crucial mechanism for the cell to maintain homeostasis. By vesicular transport the cell is able to take up cargo from the cell surface, send molecules to the plasma membrane for... Show moreEndocytosis is a crucial mechanism for the cell to maintain homeostasis. By vesicular transport the cell is able to take up cargo from the cell surface, send molecules to the plasma membrane for excretion or to regulate positioning of internalized cargo in the cell. This thesis describes the regulation of transport complexes associated to these vesicles that determines their movement in the cell. Through recruitment of RAB7GAP the GTPase Rab7 can be removed from the vesicular membrane, allowing for transport mediated by another GTPase called Arl8b.The second part of this thesis focusses on the bacterium Salmonella which manipulates the endosomal system in order to create a niche that supports its own survival. By excretion of effector molecules Salmonella imodulates the membrane content of vesicles and thereby prevents its own lysosomal degradation. This allows Salmonella to create a Salmonella containing vesicle compartment that benefits its own survival in the host cell. This thesis describes how release of these effector molecules can support transformation of host cells. These results explain the strrong correlation between gallbladder cancer and chronic S. Typhi infections observed in patients from countries like India, where S. Typhi infections are still common. Show less
Peijnenburg, W.J.G.M.; Baalousha, M.; Chen, J.; Chaudry, Q.; Kammer, F. von der; Kuhlbusch, T.A.J.; ... ; Koelmans, A.A. 2015
Proper understanding of the basic processes and specific properties of engineered nanomaterials (NMs) that modify the fate and effects of NMs is crucial for NM-tailored risk assessment. This in... Show moreProper understanding of the basic processes and specific properties of engineered nanomaterials (NMs) that modify the fate and effects of NMs is crucial for NM-tailored risk assessment. This in turn requires developers of NMs and for regulators to consider the most important parameters governing the properties, behavior and toxicity of NMs. As fate and effect studies are commonly performed in laboratory settings, mimicking to a varying extent realistic exposure conditions, it is important to be able to extrapolate results of fate and effect studies in synthetic media to realistic environmental conditions. This requires detailed understanding of the processes controlling the fate and behavior of NMs in terrestrial and aquatic media, as dependent on the composition of the medium. It is the aim of this contribution to provide background reading to the NM and media specific properties and processes that affect the fate and behavior of NMs in aquatic environments, focusing on the specific properties of NMs that modulate the interactions in the aquatic environment. A general introduction on the dominant fate determining processes of NMs is supplemented by case studies on specific classes of NMs: metal NMs, stable oxides, iron oxides, and carbon nanotubes. Based on the synthesis of the current knowledge base toward essential data and information needs, the review provides a description of the particle specific properties and the water characteristics that need monitoring in order to allow for future quantification and extrapolation of fate and behavior properties of NMs in freshwater compartments of varying composition. Show less
