The work in this thesis describes the fundamental role of Lkb1 as a conductor of metabolism-related processes in zebrafish larvae. We show that Lkb1 is essential for the regulation of glucose... Show moreThe work in this thesis describes the fundamental role of Lkb1 as a conductor of metabolism-related processes in zebrafish larvae. We show that Lkb1 is essential for the regulation of glucose metabolism, the activation of autophagy, and hematopoiesis under conditions of metabolic stress. Furthermore, we also uncovered gene transcription profiles and hematological characteristics that are specific to lkb1 larvae, and independent of metabolic stress. Finally, we illustrate and highlight the potential of lkb1 larvae as screening platform in research related to metabolism, hematopoiesis, and tumors bearing LKB1 mutations. Overall, we have strengthened the value of lkb1 zebrafish larvae as a model to study the effects of Lkb1-inactivation on various metabolism-related processes Show less
The effective treatment of tuberculosis (TB) remains a major challenge to global health. Drug-resistant Mycobacterium tuberculosis (Mtb) strains and co-infection with HIV further increase the... Show moreThe effective treatment of tuberculosis (TB) remains a major challenge to global health. Drug-resistant Mycobacterium tuberculosis (Mtb) strains and co-infection with HIV further increase the difficulty of controlling TB. Thus, under the current situation, it is essential to develop effective treatment strategies for Mtb infections. Autophagy is a lysosomal degradation process and substantial experimental evidence has demonstrated that autophagy is an important host immune defense mechanism against mycobacterial infection. However, the development of effective therapies requires a better understanding of the interaction between the host and invading pathogens to identify host processes that can be targeted. A useful tool for such studies is the zebrafish model for TB. Zebrafish can be infected with Mycobacterium marinum (Mm), which is closely related to Mtb and causes similar disease characteristics. Taking advantage of the zebrafish TB model, this thesis presents new in vivo evidence for the important function of autophagy to inhibit mycobacterial proliferation inside macrophages. Furthermore, this study supports that stimulating the innate host defense processes that are dependent on the autophagy modulator, Dram1, and the selective autophagy receptors, p62 and Optineurin, could be a useful strategy to explore for adjunctive treatment of antibiotic-resistant TB infections. Show less
This thesis describes the introduction of the zebrafish animal model to the field of proteomcis. The work presented provided the research community with the first zebrafish spectral library, which... Show moreThis thesis describes the introduction of the zebrafish animal model to the field of proteomcis. The work presented provided the research community with the first zebrafish spectral library, which is an important first step to introduce zebrafish to proteomics research. This thesis also provides proteomics resourses to automate and simplify the creation of spectral libraries. Furthermore, it describes the use of the software programme CompareMS2 to provide information on similarities across proteomics databases. In addition, the programme has shown to be applicable as a quick first analysis step on large proteomics datasets. Besides, the thesis demonstrates the advantages and applicability of a multidisciplinary approach, addressing multiple omics, exemplified by using two closeley related model species (zebrafish and common carp). Finally, an overview is given on the advantages and disadvantages of the zebrafish animal model within the field of proteomics. The practical approach to zebrafish models in proteomics described in this thesis resulted in experimental protocols, a standard spectral library and data analysis tools, and significantly contributed to maturing of the zebrafish animal model system for proteomics research. Show less
