Difference between revisions of "Dionne"

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We are interested in (1) metabolic-immune interaction and its effects on the biology of infection; and (2) cytokine signalling and its effects on immune and non-immune tissues. ''Drosophila melanogaster'' is our animal model of choice.
 
We are interested in (1) metabolic-immune interaction and its effects on the biology of infection; and (2) cytokine signalling and its effects on immune and non-immune tissues. ''Drosophila melanogaster'' is our animal model of choice.
  
Work in the lab has been funded by [http://www.bbsrc.ac.uk the Biotechnology and Biological Sciences Research Council] and [http://www.wellcome.ac.uk the Wellcome Trust].
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Work in the lab has been funded by [http://www.bbsrc.ac.uk the Biotechnology and Biological Sciences Research Council], [http://www.wellcome.ac.uk the Wellcome Trust], and [http://www.mrc.ac.uk the Medical Research Council].
  
 
==Metabolic-immune interaction and host genetics in infection==
 
==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 favor 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.
+
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. [http://www.cell.com/abstract/S0092-8674(13)01144-6 This work has recently been published in ''Cell''.]
 
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. [http://www.cell.com/abstract/S0092-8674(13)01144-6 This work has recently been published in ''Cell''.]

Revision as of 09:37, 27 March 2014

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About Us       Protocols &c.       Lab Members       Publications       Contact       Links


Welcome to the Dionne lab!

That is to say, Marc Dionne's lab, at King's College London; not to be confused with any other Dionne lab.

We are interested in (1) metabolic-immune interaction and its effects on the biology of infection; and (2) cytokine signalling and its effects on immune and non-immune tissues. 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.

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! More recently, we have been analyzing the role of an interleukin-like signal in Mycobacterium marinum infection - we hope to be able to say more about this soon.

Positions available

A funded postdoctoral position is currently available. More generally, we are always interested in hearing from potential graduate students and post-docs. If you are interested in our work, get in touch!

<wikionly>

Recent updates to the lab wiki

22 October 2017

     18:55 

(Upload log). .

[Vishnu Karthigeyan‎; Amy Nystrom‎; Cassie Riggs‎ (2×); Michael A. Finocchiaro‎ (4×); Jason Zhang‎ (4×); Carlos Mendez-Arias‎ (13×)]

     

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. . Vishnu Karthigeyan (talk | contribs) uploaded File:Rottweiler Vishnu.jpg

     

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BME100 f2017:Group12 W0800 L4‎‎ (6 changes | history) . . (+408). . [Vishnu Karthigeyan‎; Amy Nystrom‎ (2×); Jason Zhang‎ (3×)]

     

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(cur | prev) . . (+4). . Vishnu Karthigeyan (talk | contribs) (OUR TEAM)

     

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BME100 f2017:Group16 W1030 L4‎‎ (3 changes | history) . . (-17). . [Hannah Correa‎ (3×)]

     

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BME100 f2017:Group3 W1030 L4‎‎ (10 changes | history) . . (+58). . [Blake A. McCal‎; Michael A. Finocchiaro‎ (9×)]

     

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(cur | prev) . . (+1). . Michael A. Finocchiaro (talk | contribs) (OUR TEAM)

     

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