ImageInLife is a Marie Skłodowska-Curie ITN funded by the European Commission Horizon2020 programme that addresses the challenge of understanding how cells behave to build organisms as complex as vertebrates. The project will run for 4 years from January 2017. It brings together leading European research groups in the field and partners from companies that aim to commercialise corresponding tools. The project is dedicated to the training of European experts in advanced microscopy solutions for imaging vertebrate development and disease processes at cellular or subcellular levels.

Prof. Annemarie Meijer (training coordinator of the network) and Dr. Marcel Schaaf from the Institute of Biology participate in this network with two PhD projects taking advantage of the world class facilities for bioimaging at the Cell Observatory of the Science Faculty.

The well-established zebrafish tuberculosis disease model is used in the first PhD project to study how mycobacteria hide in subcellular compartments of immune cells and induce these infected leukocytes to form organised cellular structures, called granulomas, which are the hallmark structures of mycobacterial infections and key to understand the pathogenesis of tuberculosis. Fluorescent reporter zebrafish lines are used to study immune defence responses (such as cytokine/chemokine activation and autophagy) and subcellular mycobacterial localisation during granuloma formation. These host-pathogen interaction processes will be visualized down to the ultrastructural level by correlating the confocal microscopy images with electron microscopy analysis, in particular block face scanning electron microscopy.

The second PhD project focuses on single molecule microscopy in zebrafish embryos and is carried out in collaboration with Dr. John van Noort at the Leiden Institute of Physics. This project builds on our recent work showing the first application of single-molecule microscopy in zebrafish embryos to study the mobility of individual fluorescent proteins in the membrane of the outer cell layer of the epidermis. In this project we aim to develop new strategies for protein tagging with fluorescent dyes and extend the possibilities of single-molecule microscopy to non-membrane proteins and proteins in sub-epithelial cell layers. TIRF, light sheet, and 2-photon microscopy setups will be used. The developed technology will be applied to image single molecules (chemokines and receptors, autophagy markers) in embryos and their dynamics in leukocytes during mycobacterial infection of zebrafish embryos.

• Meijer AH (2016) Protection and pathology in TB: learning from the zebrafish model. Semin Immunopathol. 38:261-7
• Hosseini R, Lamers GE, Soltani HM, Meijer AH, Spaink HP, Schaaf MJ (2016) Efferocytosis and extrusion of leukocytes determine the progression of early mycobacterial pathogenesis. J Cell Sci. pii: jcs.135194
• van der Vaart M, Korbee CJ, Lamers GEM, Tengeler AC, Hosseini R, Haks MC, Ottenhoff THM, Spaink HP, Meijer AH (2014) The DNA Damage-Regulated Autophagy Modulator DRAM1 links mycobacterial recognition via TLR-MYD88 to autophagic defense. Cell Host Microbe 15:753-67
• Hosseini R, Lamers GE, Hodzic Z, Meijer AH, Schaaf MJ, Spaink HP (2014) Correlative light and electron microscopy imaging of autophagy in a zebrafish infection model. Autophagy 10:1844-57
• Schaaf MJ, Koopmans WJ, Meckel T, van Noort J, Snaar-Jagalska BE, Schmidt TS, Spaink HP (2009) Single-molecule microscopy reveals membrane microdomain organization of cells in a living vertebrate. Biophys J. 97:1206-14

• correlative light and electron microscopy
• development & disease
• host-microbe interactions
• host-pathogen interaction
• imaging
• infectious disease
• innate immunity
• single molecule microscopy
• tuberculosis

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