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Final Report Summary - ROLE OF ALVEOLAR MFS (Study of the functional role of Alveolar Macrophages in vivo.)

Macrophages were originally identified by the Nobel laureate Ilya Metchnikoff as cells specialized in the killing of microorganisms more than 100 years ago. However, genetic profiling of macrophages from various tissues has demonstrated the astonishing diversity of macrophages, suggesting that each macrophage is profoundly adapted to its tissue of residence and performs unique local functions. However, what these unique functions might be is only poorly understood. Unfortunately, the scientific macrophage community has not been able to generate the tools that are necessary to investigate the functions of specific tissue-resident macrophages in vivo. With this Marie-Curie Career Integration Grant (CIG) project my ambition was to generate new scientific tools to study liver and lung resident macrophages that go beyond the current state of the art. In the first part of the project, we have first performed a gene expression profile of these cells. This is on the one hand used to perform in silico prediction of the main functions of these cells and on the other hand used to screen for genes specific for these cells so that we can construct novel scientific tools to study these cells in vivo. Altogether these unique tools will permit to: (i) identify bona fide lung and liver specific macrophages unambiguously in vivo and ex vivo, (ii) specifically deplete these macrophages in vivo, (iii) knock-down genes of interest exclusively in liver and lung macrophages. Most of these tools are now ready and function well, which opens exciting possibilities to finally unravel the function of these cells that were discovered more than 100 years ago. The Marie Curie Career Integration Grant (CIG) has also functioned as seed funding to launch my own line of research. Using the exciting new data from the CIG project I have been able to propose a novel and ambitious research project to the Odysseus Program and have been able to obtain this competitive Belgian grant. What makes the Odysseus program unique is the combination of a permanent position at a Flemish university, which has resulted in me being appointed Assistant Professor in 2015, and sufficient project funding to establish my own research team. I have also obtained an ERC Consolidator Grant in 2016 (starting in 2017). This will result my appointment as independent PI in the Inflammation Research Center (IRC). As such the CIG grant has not only been crucial to initiate a novel line of successful cutting edge research, it has also allowed me to boost my academic career and pave the way towards long-term integration in what I consider to be the best research institute for Immunological research in Belgium, i.e. the Inflammation Research Center from the VIB & the Ghent University.

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