Highlights

Prof.dr. Geert van den Bogaart

The laboratory of Geert van den Bogaart is positioned at the interface of microbial physiology, chemistry, microscopy and immunology. The goal of his research is to understand and ultimately tailor membrane trafficking pathways in immune cells to cure and prevent disease. His fascination in science is how the immune system can efficiently respond to a diverse range of threats while at the same time maintain immune homeostasis and not respond to harmless commensals. His lab studies human immune cells in a range of diseases, mainly inflammatory bowel disease and cancer. The central focus of his research are the cellular mechanisms that lead to uptake and degradation of foreign antigen and the trafficking cascades that underlie antigen presentation and cytokine release by phagocytes of the immune system. To resolve the membrane trafficking routes of immune cell function, Van den Bogaart develops and applies advanced microscopy techniques and novel chemical tools. His lab follows a multidisciplinary approach which combines advanced cell biology on primary blood-isolated immune cells, with a bottom-up approach where complex trafficking pathways are reconstituted in precisely definable in vitro systems.

A recent highlight is the development of a new FRET-FLIM based assay for quantitative visualization of SNARE proteins, the engines that regulate intracellular organelle fusion [1]. This approach was used to identify the cellular defects causing the symptoms of patients with a missense substitution in the second starting methionine of the gene coding for the SNARE-protein Syntaxin-5, which causes early fatal multisystem disease. It was found that anterograde ER-Golgi trafficking was impaired due to loss of the Syntaxin-5-short isoform, resulting is mislocalization of glycosyltransferase enzymes, and impaired protein glycosylation [2].

[1] Verboogen DRJ, González Mancha N, ter Beest M & van den Bogaart G (2017) Fluorescence lifetime imaging microscopy reveals rerouting of SNARE trafficking driving dendritic cell activation. eLife 6: e23525; DOI: https://doi.org/10.7554/elife.23525

[2] Linders PTA, Gerretsen E, ……, ter Beest M, Lefeber D & van den Bogaart G (2021) Congenital disorder of glycosylation caused by starting site-specific variant in syntaxin-5. Nature Communications. 12: 6227; DOI: https://doi.org/10.1038/s41467-021-26534-y