Persistent URL of this record https://hdl.handle.net/1887/3289526
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Boosting the host immune system to fight tuberculosis
zebrafish embryo model for TB to evaluate potential anti-TB host-directed therapeutics (HDTs) arising from in vitro screens. Although in vitro screens for HDTs using cellular models can be performed at high throughput, a limiting step is the validation in whole animal models and translation of results to clinical applications. Due to the complex infection dynamics of mycobacteria, the use of whole animal models is indispensable in research into TB and the zebrafish model has contributed key findings about host-pathogen dynamics during mycobacterial infection. One of the most promising host targets of HDTs is autophagy, which is recognized as an important host-protective pathway. Boosting autophagy levels using...Show moreNew drugs for use as tuberculosis (TB) treatment are needed due to the constrains of classical antibiotics against TB and the rise of antibiotic-resistant strains, making TB a harder and harder disease to treat. This thesis is focused on using the in vivo whole animal
zebrafish embryo model for TB to evaluate potential anti-TB host-directed therapeutics (HDTs) arising from in vitro screens. Although in vitro screens for HDTs using cellular models can be performed at high throughput, a limiting step is the validation in whole animal models and translation of results to clinical applications. Due to the complex infection dynamics of mycobacteria, the use of whole animal models is indispensable in research into TB and the zebrafish model has contributed key findings about host-pathogen dynamics during mycobacterial infection. One of the most promising host targets of HDTs is autophagy, which is recognized as an important host-protective pathway. Boosting autophagy levels using HDTs could be a way to overcome the pathogen’s autophagy evasion strategies and could therefore be a promising therapeutic route. For this thesis we took advantage of the possibilities of the zebrafish embryo model for TB and the zebrafish toolkit to study several autophagy-modulating HDTs as potential anti-TB drugs.
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- All authors
- Boland, R.
- Supervisor
- Meijer, A.H.; Spaink, H.P.
- Co-supervisor
- Vaart, M. van der
- Committee
- Wezel, G.P. van; Snaar-Jagalska, B.E.; Barz, M.; Ottenhoff, T.H.M.; Houben, E.N.G.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Institute of Biology Leiden (IBL) , Faculty of Science , Leiden University
- Date
- 2022-04-28
- ISBN (print)
- 9789464194906
Funding
- Sponsorship
- This publication is part of the project Novel immunomodulatory drugs for tuberculosis treatment (with project number 13259) of the research programme Open Technology Programme which is financed by the Dutch Research Council (NWO).