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==Welcome to the Dionne lab!==
 
==Welcome to the Dionne lab!==
  
We are interested in (1) the effects of host genetics on the biology of infection; and (2) the physiological control of metabolic balance.
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That is to say, Marc Dionne's lab, at King's College London; not to be confused with any other Dionne lab.
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We are interested in (1) the effects of host genetics 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.
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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].
  
 
==Host genetics and the biology of infection==
 
==Host genetics and the biology of infection==
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All of our experiments originate from a simple genetic screen. Mutant flies are infected with ''Mycobacterium marinum'', a bacterium closely-related to the causative agent of tuberculosis, or with ''Mycobacterium smegmatis'', a related non-pathogen. We select lines of flies that die more quickly or more slowly than wild-type controls and identify the mutation that gives rise to this phenotype. We then try to understand what this phenotype tells us about the function of the mutated gene.
 
All of our experiments originate from a simple genetic screen. Mutant flies are infected with ''Mycobacterium marinum'', a bacterium closely-related to the causative agent of tuberculosis, or with ''Mycobacterium smegmatis'', a related non-pathogen. We select lines of flies that die more quickly or more slowly than wild-type controls and identify the mutation that gives rise to this phenotype. We then try to understand what this phenotype tells us about the function of the mutated gene.
  
So far, our work on this system has focused on the mechanisms of pathogenesis. We have found that this infection causes progressive loss of metabolic stores, similar to the wasting seen in people with tuberculosis. We have shown that, in the fly, this wasting effect is caused partly by systemic failures in anabolic signals via the insulin effector kinase Akt. We are now working to try to understand how infection causes this defect in anabolic signalling. We also have mutants that affect other aspects of disease; we are working with these mutants to understand  other aspects of disease pathogenesis as well as how the fly immune system fights Mycobacterial infections.
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So far, our work on this system has focused on the mechanisms of pathogenesis. We have found that this infection causes progressive loss of metabolic stores, broadly similar to the wasting seen in people with tuberculosis. We have shown that, in the fly, this wasting effect is caused partly by systemic failures in anabolic signals via the insulin effector Akt and the TOR effector p70 S6 kinase.
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Most recently, we have shown that 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. [http://www.cell.com/abstract/S0092-8674(13)01144-6 This work has recently been published in ''Cell''.]
  
==Physiological control of metabolic balance==
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==Cytokines and cytokine signalling==
  
As mentioned above, we've found that infection with ''M marinum'' causes serious metabolic defects in ''Drosophila''. At least some of these effects are due to changes in signalling pathways whose roles in metabolic control are largely unexplored or completely unknown. This has led us to examine the roles of these pathways in metabolic control in healthy animals so that we can then understand the effects of infection-induced perturbation of these pathways.
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In the course of screening, we find a lot of molecules and pathways that end up being involved in cytokine signalling and its consequences. One aspect of this is the metabolic effects of infection, which appear to result from high levels of cytokine expression over several days. Cytokines also regulate the realized immune response of the fly, much as they do in mammals.
  
This work is preliminary but is very exciting - we hope to be able to say more soon!
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Some time back, we published some of this work in ''Current Biology'', showing 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. [http://www.cell.com/current-biology/abstract/S0960-9822(11)00954-7 Check it out!]
  
 
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Revision as of 05:03, 28 September 2013

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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) the effects of host genetics 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 and the Wellcome Trust.

Host genetics and the biology of infection

Different individuals show different levels of resistance to infections and develop different pathologies in response to infections. We are interested in why this is the case. We use the fruitfly Drosophila melanogaster as a model host to study these questions; this allows us to screen for genes that affect the progress of infection in a rapid and unbiased fashion.

All of our experiments originate from a simple genetic screen. Mutant flies are infected with Mycobacterium marinum, a bacterium closely-related to the causative agent of tuberculosis, or with Mycobacterium smegmatis, a related non-pathogen. We select lines of flies that die more quickly or more slowly than wild-type controls and identify the mutation that gives rise to this phenotype. We then try to understand what this phenotype tells us about the function of the mutated gene.

So far, our work on this system has focused on the mechanisms of pathogenesis. We have found that this infection causes progressive loss of metabolic stores, broadly similar to the wasting seen in people with tuberculosis. We have shown that, in the fly, this wasting effect is caused partly by systemic failures in anabolic signals via the insulin effector Akt and the TOR effector p70 S6 kinase.

Most recently, we have shown that 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. This work has recently been published in Cell.

Cytokines and cytokine signalling

In the course of screening, we find a lot of molecules and pathways that end up being involved in cytokine signalling and its consequences. One aspect of this is the metabolic effects of infection, which appear to result from high levels of cytokine expression over several days. Cytokines also regulate the realized immune response of the fly, much as they do in mammals.

Some time back, we published some of this work in Current Biology, showing 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!

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Recent updates to the lab wiki

23 November 2017

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