University of Cambridge > > Morphogenesis Seminar Series > Opening doors and boosting energy: cellular programs that enable macrophage tissue infiltration.

Opening doors and boosting energy: cellular programs that enable macrophage tissue infiltration.

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If you have a question about this talk, please contact Elena Scarpa.

My lab seeks to understand the cellular mechanisms underlying homeostasis, focusing on the immune system. We are currently examining how immune cells can move through tissue barriers. This capacity underlies the establishment of tissue resident macrophages that regulate physiology, the capacity of multiple immune cell types to control infection, and the emerging field of immuno-oncology. We utilize the developmental migration of Drosophila melanogaster macrophages as they penetrate a region of the embryo as a model, and extend those findings into higher organisms. I will talk about two stories illustrating the importance of cellular programs acting both within the surroundings and within the macrophages. We have found through two-color live imaging, genetics and optogenetics that initial macrophage infiltration is controlled by the rate of division of the surrounding cells, providing a powerful new perspective on this process. We have shown that division disassembles the focal adhesions in surrounding tissue, removing a steric hindrance for macrophages to enter. In collaborative work with the Clevers lab, we have shown that this paradigm holds also for the entry of macrophages into mouse organoids, underscoring the power of the fly system to identify broadly applicable principles for invasion. Second I will describe a new program we found acting within Drosophila macrophages to enable infiltration by boosting mitochondrial energy production. Through genetics, RNA seq, metabolomics and direct mitochondrial assays, we show that a previously unstudied nuclear factor increases energy production by raising levels of three proteins; these components coordinate metabolic biochemistry and the translation of a subset of mitochondrial proteins due to higher ribosome levels. Two mammalian orthologs of this nuclear factor can rescue both invasion and mitochondrial defects, arguing the capacity to positively regulate energy production is conserved; one ortholog is strongly linked in GWAS studies to Alzheimer’s. I will also outline our future directions in both areas.

This talk is part of the Morphogenesis Seminar Series series.

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