Dionne
Welcome to the Dionne lab!
That is to say, Marc Dionne's lab, at Imperial College London; not to be confused with any other Dionne lab.
We are interested in the ways in which host genotype affects the biology of bacterial infection. Drosophila melanogaster is our animal model of choice.
Work in the lab has been funded by the Biotechnology and Biological Sciences Research Council, the Wellcome Trust, and the Medical Research Council.
A BBSRC-funded postdoctoral position is available in the lab! If you're interested, get in touch, or apply here!
Metabolic-immune interaction and host genetics in infection
It has been known for centuries that chronic infections cause systemic metabolic disruption, but it is fundamentally unclear why and how these events are linked. Does metabolic disruption somehow facilitate the host response to infection? If so, how? We address these fundamental biological questions by analyzing pathogenic infections and their consequences in the fruit-fly Drosophila melanogaster. We use classical Drosophila genetics, computational analysis and modeling of gene expression, biochemistry, and intravital microscopy to probe the metabolic-immune interface.
One pathogen of particular interest to us is Mycobacterium marinum. We have previously shown that flies infected with M. marinum exhibit progressive loss of metabolic stores accompanied by mild hyperglycemia. We have shown that these effects are caused, in part, by systemic disruption of signaling via the anabolic effector kinases Akt and p70 S6 kinase. The transcription factor MEF2 responds to nutrient signals to regulate expression of both immune effectors and anabolic enzymes. Remarkably, though MEF2 promotes the expression of both groups of genes, its choice of targets is regulated by a conserved phosphorylation that alters its affinity for the TATA binding protein. It appears that the disruption of anabolic kinase activity may be required to permit MEF2 to drive the antibacterial response. This work has recently been published in Cell.
Ongoing work continues to explore other metabolic inputs into MEF2, other targets of MEF2 in its two discrete physiological states, and the pathways by which infection disrupts anabolic kinase activity.
Cytokines and cytokine signalling
In the course of screening for mutants with defective responses to M. marinum, we find a lot of molecules and pathways that end up being involved in cytokine signalling and its consequences. Cytokines regulate the realized immune response of the fly, much as they do in mammals; they also can be significant direct drivers of pathology due to effects on immune and nonimmune target tissues. However, very little is known about the biology of cytokines in Drosophila melanogaster, especially in the context of bacterial infections.
Some time back, we showed that two different TGF-betas regulate fly immunity, each inhibiting a specific arm of the immune response, and each being produced by only a subset of phagocytes. Check it out!
We've also done some exciting work in collaboration with Frederic Geissmann's lab on the role of JAK-STAT signalling in flies on a high-fat diet; you can read about it here. We continue to work on the roles of this pathway in Mycobacterium marinum infection and in muscle physiology—we hope to be able to say more about these soon.
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22 January 2021
| 16:32 | User:Jessica A. DaMota diffhist +346 Jessica A. DaMota talk contribs →COVID-19 Research Project: uploaded annotated bibliography | ||||
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16:26 Jessica A. DaMota talk contribs uploaded File:Annotated Bibliography JDamota.pdf (Annotated Bibliography of COVID-19 research focused on TMPRSS2 SNPs written by Jessica DaMota.) | ||||
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16:24 Jessica A. DaMota talk contribs uploaded File:Annotated Bibliography.pdf (Annotated Bibliography of COVID-19 research focused on TMPRSS2 SNPs.) | ||||
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14:32 Jessica A. DaMota talk contribs uploaded File:TMPRSS4 HHPRED.png (3D visual model of TMPRS44 generated using HHPred Software) | ||||
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13:54 Mking44 talk contribs uploaded File:King Title&AnnotatedBibliography.pdf | ||||
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12:34 Adinulos talk contribs uploaded File:Dinulos TMPRSS2Report.pdf (added tmprss2 report) | ||||
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11:54 Adinulos talk contribs uploaded File:Dinulos AnnotatedBib.pdf (uploaded annotated bibliography) | ||||
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