Dionne: Difference between revisions

From OpenWetWare
Jump to navigationJump to search
No edit summary
No edit summary
(5 intermediate revisions by the same user not shown)
Line 6: Line 6:
That is to say, Marc Dionne's lab, at King's College London; not to be confused with any other 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) the physiological control of metabolic balance. ''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 is funded by [http://www.bbsrc.ac.uk the Biotechnology and Biological Sciences Research Council] and [http://www.wellcome.ac.uk the Wellcome Trust].
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].


==We've moved!==
==Metabolic-immune interaction and host genetics in infection==


The lab has moved from its original digs (on the 27th and 28th floors of Guy's Tower) across the street to New Hunt's House in order to be part of the new Centre for the Molecular and Cellular Biology of Inflammation. Our academic affiliation will be changing to the Peter Gorer Department of Immunobiology, DIIID, School of Medicine. Directions and postal addresses have been corrected on the [http://dionne.openwetware.org/Contact.html Contact] page.
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.


==Host genetics and the biology of infection==
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''.]


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.
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.


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.
==Cytokines and cytokine signalling==


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.
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.


==Physiological control of metabolic balance==
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. [http://www.cell.com/current-biology/abstract/S0960-9822(11)00954-7 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.


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.
==Positions available==


This work is preliminary but is very exciting - we hope to be able to say more soon!
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>
<wikionly>

Revision as of 09:37, 27 March 2014

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

List of abbreviations:
N
This edit created a new page (also see list of new pages)
m
This is a minor edit
b
This edit was performed by a bot
(±123)
The page size changed by this number of bytes

26 April 2024

N    08:47  The Paper that Launched Microfluidics - Xi Ning‎‎ 2 changes history +16,815 [Xning098‎ (2×)]
     
08:47 (cur | prev) −1 Xning098 talk contribs (→‎Introduction)
N    
08:43 (cur | prev) +16,816 Xning098 talk contribs (Created page with "{{Template:CHEM-ENG590E}} ==Introduction== Microfluidics is the science and technology of systems that process or manipulate small (10 <sup> -18 </sup> to 10 <sup>−18 </sup> litres) amounts of fluids, using channels with dimensions of tens to hundreds of micrometres, as stated by George Whitesides. <sup> https://doi.org/10.1038/nature05058 1 </sup>. Microfluidic devices are microchemical systems such as labs on the chip, organs on the chip and plants on the chip....")
     08:43  CHEM-ENG590E:Wiki Textbook‎‎ 3 changes history 0 [Xning098‎ (3×)]
     
08:43 (cur | prev) 0 Xning098 talk contribs Tag: Manual revert
     
08:42 (cur | prev) 0 Xning098 talk contribs Tag: Manual revert
     
08:41 (cur | prev) 0 Xning098 talk contribs
     08:40  The paper that launched microfluidics - Xi Ning‎‎ 15 changes history +250 [Xning098‎ (15×)]
     
08:40 (cur | prev) +18 Xning098 talk contribs (→‎Significance)
     
08:36 (cur | prev) 0 Xning098 talk contribs (→‎Significance)
     
08:34 (cur | prev) +37 Xning098 talk contribs (→‎Significance)
     
08:31 (cur | prev) +3 Xning098 talk contribs (→‎Significance)
     
08:30 (cur | prev) +8 Xning098 talk contribs (→‎Significance)
     
08:28 (cur | prev) −31 Xning098 talk contribs (→‎Significance)
     
08:22 (cur | prev) −1 Xning098 talk contribs (→‎Electrokinetic effect)
     
08:21 (cur | prev) −2 Xning098 talk contribs (→‎Separation and quantification)
     
08:19 (cur | prev) 0 Xning098 talk contribs (→‎Sample dilution)
     
08:19 (cur | prev) 0 Xning098 talk contribs (→‎Sample dilution)
     
08:18 (cur | prev) 0 Xning098 talk contribs (→‎Separation and quantification)
     
08:17 (cur | prev) −1 Xning098 talk contribs (→‎Sample dilution)
     
08:17 (cur | prev) +1 Xning098 talk contribs
     
08:14 (cur | prev) 0 Xning098 talk contribs (→‎Microfluidic set-ups and its efficacy)
     
08:03 (cur | prev) +218 Xning098 talk contribs
     08:20  (Upload log) [Xning098‎ (6×)]
     
08:20 Xning098 talk contribs uploaded File:XiNingFigure2.jpeg
     
08:14 Xning098 talk contribs uploaded File:Figure4Drawn.XiNing.jpeg
     
08:00 Xning098 talk contribs uploaded File:DrawnFigure4XiNing.jpeg
     
07:38 Xning098 talk contribs uploaded File:XiNingDrawnSetup2.png
     
07:35 Xning098 talk contribs uploaded a new version of File:Figure 2 Set-up1.png
     
07:24 Xning098 talk contribs uploaded File:DrawnElectoosmoticflow.jpeg
     05:25  Ernesto-Perez-Rueda:Contact diffhist −94 Ernesto Perez-Rueda talk contribs

25 April 2024

     23:55  Flow and Pattern Asymmetries‎‎ 23 changes history +1,186 [Courtneychau‎ (23×)]
     
23:55 (cur | prev) −14 Courtneychau talk contribs (→‎Mixing on the Microfluidic Scale)
     
23:55 (cur | prev) −43 Courtneychau talk contribs (→‎Reynolds Number (Re))
     
23:55 (cur | prev) −46 Courtneychau talk contribs (→‎Péclet Number (Pe))
     
23:55 (cur | prev) −31 Courtneychau talk contribs (→‎Stokes Flow)
     
23:54 (cur | prev) −151 Courtneychau talk contribs (→‎Stokes Flow)
     
23:50 (cur | prev) +184 Courtneychau talk contribs (→‎References)
     
23:46 (cur | prev) 0 Courtneychau talk contribs (→‎Active Mixing Methods)
     
23:46 (cur | prev) +1 Courtneychau talk contribs (→‎Passive Mixing Methods)
     
23:45 (cur | prev) 0 Courtneychau talk contribs (→‎Chaotic Advection)
     
23:44 (cur | prev) 0 Courtneychau talk contribs (→‎Mixing on the Microfluidic Scale)
     
23:43 (cur | prev) +28 Courtneychau talk contribs (→‎Stokes Flow)
     
23:39 (cur | prev) +1 Courtneychau talk contribs (→‎Stokes Flow) Tag: Manual revert
     
23:38 (cur | prev) −1 Courtneychau talk contribs (→‎Stokes Flow)
     
23:37 (cur | prev) +11 Courtneychau talk contribs
     
23:36 (cur | prev) +15 Courtneychau talk contribs
     
23:33 (cur | prev) 0 Courtneychau talk contribs (→‎References)
     
23:30 (cur | prev) +3 Courtneychau talk contribs (→‎Passive Mixing Methods)
     
23:28 (cur | prev) −426 Courtneychau talk contribs
     
23:16 (cur | prev) +1,656 Courtneychau talk contribs (→‎References)
     
23:14 (cur | prev) 0 Courtneychau talk contribs (→‎Applications of Asymmetric Flow)
     
23:13 (cur | prev) 0 Courtneychau talk contribs (→‎Active Mixing Methods)
     
23:12 (cur | prev) −1 Courtneychau talk contribs (→‎Passive Mixing Methods)
     
23:11 (cur | prev) 0 Courtneychau talk contribs (→‎Microfluidic Mixers)

</wikionly>

<nonwikionly> This page was created using Open Wetware.</nonwikionly>