In this thesis I explored the ins and outs of the multivesicular body, the pathways that intersect at this central endocytic compartment, the dynamics governing its lumen and how such processes... Show moreIn this thesis I explored the ins and outs of the multivesicular body, the pathways that intersect at this central endocytic compartment, the dynamics governing its lumen and how such processes impact various fields of cell biology and disease. Show less
Dit proefschrift bevat onderzoek over verschillende processen binnen het intracellulaire domein. Als eerst wordt er onderzocht hoe een cel zijn oplosbare eiwitten in de correcte compartimenten... Show moreDit proefschrift bevat onderzoek over verschillende processen binnen het intracellulaire domein. Als eerst wordt er onderzocht hoe een cel zijn oplosbare eiwitten in de correcte compartimenten krijgt na mitosis. Het tweede omschrijft een mechanisme dat verantwoordelijk is voor het structureren van het endoplasmatisch reticulum. Als derde werd onderzocht wat voorn rol het eiwit MOSPD2 vervult binnen contacten tussen het ER, Golgi apparatus en lysosomen. Show less
Diabetes mellitus type 2 (DM) is a major risk factor for developing active tuberculosis (TB) disease, yet the causal mechanisms driving this association remain largely elusive. As the incidence of... Show moreDiabetes mellitus type 2 (DM) is a major risk factor for developing active tuberculosis (TB) disease, yet the causal mechanisms driving this association remain largely elusive. As the incidence of DM is rising, especially in TB endemic countries, it is important to identify the relevant immunological and metabolic processes that underlie TB-DM comorbidity, because such insights will facilitate optimal treatment, diagnosis and prevention. In this thesis, we have started to unravel key factors underlying the association between TBand DM using two approaches. Firstly, we identified and analyzed human macrophage subsets and studied the interactions between these human cells and a major pathogen, Mycobacterium tuberculosis (Mtb), and the specific metabolic changes involved using well-controlled in vitro systems. Next, we employed metabolomics to determine the impact of concurrent TB-DM on circulating metabolites in patient cohorts ex vivo. In this thesis we present evidence derived from in vitro experiments and from ex vivo observational data which collectively suggest a pathogenic role of atherogenic lipid species during TB development. Show less
