Signals from immune cells to other tissues are critical regulators of physiology and pathophysiology. Conversely, signals from non-immune tissues are often critical regulators of the immune response. However, these signals are poorly-understood biologically. The Dionne lab uses the fruit-fly Drosophila melanogaster to tease apart these interactions. The virtue of Drosophila for this kind of work is two-fold: its small size, quick generation time and extensively-annotated genome make it tractable via forward and reverse genetics and bioinformatic techniques, while its mechanisms of physiological regulation and the components of its immune system are recognizably closer to those of humans than those of other invertebrate model systems.<br />
Our current focus is on the infection of Drosophila with Mycobacterium marinum. M marinum causes an invariably-lethal infection in Drosophila, with many similarities to human tuberculosis (Dionne et al., Infect Immun 2002; Dionne et al., Curr Biol 2006). We have previously described how this infection disrupts insulin signalling in the host, with resulting defects in anabolism that result in a cachexia-like condition. One current goal is to understand the mechanisms that generate this blockade to insulin signalling. As an outgrowth of this work, we are also investigating the mechanisms by which metabolic balance is ordinarily maintained. A second project in the lab is focussed on continuing our screen for host factors that regulate this infection; we have recently complemented the unbiased genetic approach with which we began with a more-targeted approach based on a bioinformatic survey of transcription-factor binding to genomic loci. A third project, in collaboration with the Geissmann laboratory, focuses on developing imaging techniques and genetic tools with which we can refine our understanding of the development and function of myeloid lineages in the fly.<br />
Our longer-term goal is to develop a full understanding of the ways immune and non-immune tissues interact in healthy animals; how these interactions are altered by infection and inflammation; and how inflammatory responses are regulated. We hope to be able to translate our findings in the fly to mammalian models and ultimately to the clinical context.
Genetics of innate immunity and the origins of immune-induced pathology
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):