Difference between revisions of "Dionne"

From OpenWetWare
Jump to: navigation, search
(One intermediate revision 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) 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].
+
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].
  
==Host genetics and the biology of infection==
+
==Metabolic-immune interaction and host genetics in 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.
+
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.
  
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.
+
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''.]
  
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.
+
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.
  
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''.]
+
==Cytokines and cytokine signalling==
  
==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. [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.
  
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.
+
==Positions available==
  
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!]
+
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

Imperial-banner.png

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

25 September 2017

     17:38  User:Oww Bot‎ (diff | hist) . . (-956). . Yar (talk | contribs) (it me)

     17:36 

(User rights log). .

[Yar‎ (13×)]

     

17:36

. . Yar (talk | contribs) changed group membership for Oww Bot from bot and administrator to bot ‎

     

17:33

. . Yar (talk | contribs) changed group membership for Yeem from administrator to (none) ‎

     

17:33

. . Yar (talk | contribs) changed group membership for Ricardo Vidal from administrator to (none) ‎

     

17:33

. . Yar (talk | contribs) changed group membership for Reshma P. Shetty from bureaucrat and administrator to (none) ‎

     

17:32

. . Yar (talk | contribs) changed group membership for Rehears from bureaucrat and administrator to (none) ‎

     

17:31

. . Yar (talk | contribs) changed group membership for Lorrie LeJeune from bureaucrat and administrator to (none) ‎

     

17:31

. . Yar (talk | contribs) changed group membership for Jeff Brock from bureaucrat, dropboxuser and administrator to dropboxuser ‎

     

17:31

. . Yar (talk | contribs) changed group membership for Jason R. Kelly from bureaucrat and administrator to (none) ‎

     

17:31

. . Yar (talk | contribs) changed group membership for Ilya from bureaucrat, developer and administrator to developer ‎

     

17:30

. . Yar (talk | contribs) changed group membership for Bill Flanagan from bureaucrat and administrator to (none) ‎

     

17:30

. . Yar (talk | contribs) changed group membership for Barry Canton from bureaucrat and administrator to (none) ‎

     

17:29

. . Yar (talk | contribs) changed group membership for Austin J. Che from bureaucrat and administrator to (none) ‎

     

17:29

. . Yar (talk | contribs) changed group membership for Administrator from bureaucrat, developer and administrator to developer ‎

     17:35  User:Yar‎ (diff | hist) . . (+26). . Yar (talk | contribs) (my name)

     17:34 

(Move log). .

[Yar‎ (5×)]

     

17:34

. . Yar (talk | contribs) moved page User talk:Yardena Cohen to User talk:Yar(Automatically moved page while renaming the user "Yardena Cohen" to "Yar")

     

17:34

. . Yar (talk | contribs) moved page User:Yardena Cohen/Notebook/attempt/Entry Base to User:Yar/Notebook/attempt/Entry Base(Automatically moved page while renaming the user "Yardena Cohen" to "Yar")

     

17:34

. . Yar (talk | contribs) moved page User:Yardena Cohen/Notebook/attempt to User:Yar/Notebook/attempt(Automatically moved page while renaming the user "Yardena Cohen" to "Yar")

     

17:34

. . Yar (talk | contribs) moved page User:Yardena Cohen/Notebook to User:Yar/Notebook(Automatically moved page while renaming the user "Yardena Cohen" to "Yar")

     

17:34

. . Yar (talk | contribs) moved page User:Yardena Cohen to User:Yar(Automatically moved page while renaming the user "Yardena Cohen" to "Yar")

     17:34 (User rename log) . . Yar (talk | contribs) renamed user Yardena Cohen (108 edits) to Yar(shorter)
     17:28  OpenWetWare:Bureaucrats‎ (diff | hist) . . (-58). . Yar (talk | contribs) (it me)
     17:28  OpenWetWare:Administrators‎ (diff | hist) . . (-187). . Yar (talk | contribs) (it me)

     17:21 

User:Yardena Cohen‎‎ (3 changes | history) . . (+501). . [Yar‎ (3×)]

     

17:21

(cur | prev) . . (+84). . Yar (talk | contribs) (link to 1.13.2 announcement from 2008...)

     

17:16

(cur | prev) . . (+4). . Yar (talk | contribs) (contact link)

     

17:15

(cur | prev) . . (+413). . Yar (talk | contribs) (allow myself to introduce myself)

     17:17  OpenWetWare:Mailing lists‎ (diff | hist) . . (-2,426). . Yar (talk | contribs) (update)
     17:15  CONJ606:Schedule‎ (diff | hist) . . (0). . Maureen E. Hoatlin (talk | contribs) (Week-by-Week Schedule Summary)

     16:32 

PrivateWikis‎‎ (2 changes | history) . . (-8). . [Yar‎ (2×)]

     

16:32

(cur | prev) . . (+3). . Yar (talk | contribs) (23)

     

16:31

(cur | prev) . . (-11). . Yar (talk | contribs) (new contact page)

     16:32 

New server‎‎ (5 changes | history) . . (+718). . [Yar‎ (5×)]

     

16:32

(cur | prev) . . (+26). . Yar (talk | contribs) (private wikis link)

     

16:23

(cur | prev) . . (+157). . Yar (talk | contribs) (check spam folder)

     

14:35

(cur | prev) . . (-17). . Yar (talk | contribs) (idk when searches will work)

     

14:34

(cur | prev) . . (+267). . Yar (talk | contribs) (rearrange, more info on passwords & emails)

     

14:27

(cur | prev) . . (+285). . Yar (talk | contribs) (confirm emails)

     14:28  Main Page‎ (diff | hist) . . (+75). . Yar (talk | contribs) (confirm email)

     14:09 

(User creation log). .

[Yar‎ (2×)]

     

14:09

. . User account Abhilash (talk | contribs) was created by Yar (talk | contribs) and password was sent by email ‎

     

14:09

. . User account Jrajbhandary (talk | contribs) was created by Yar (talk | contribs) and password was sent by email ‎

     12:14 

(Upload log). .

[Trevor S. Heaton‎; Anshul Krishnan‎ (2×); Vinh T. Le‎ (3×)]

     

12:14

. . Vinh T. Le (talk | contribs) uploaded File:ZOLA9252017 3.PNG

     

12:14

. . Vinh T. Le (talk | contribs) uploaded File:ZOLA9252017 2.PNG

     

12:13

. . Vinh T. Le (talk | contribs) uploaded File:ZOLA9252017 1.PNG

     

09:18

. . Trevor S. Heaton (talk | contribs) uploaded a new version of File:Graph 1.PNG

     

06:18

. . Anshul Krishnan (talk | contribs) uploaded File:BME100TempVTrials.png

     

06:10

. . Anshul Krishnan (talk | contribs) uploaded File:BME100L3Temp.png

24 September 2017

N    22:33  MediaWiki:Tagline‎ (diff | hist) . . (+16). . Yar (talk | contribs) (less parsing)
N    22:32  MediaWiki:Pagetitle-view-mainpage‎ (diff | hist) . . (+11). . Yar (talk | contribs) (less parsing)
N    22:32  MediaWiki:Opensearch-desc‎ (diff | hist) . . (+16). . Yar (talk | contribs) (english-only?)
N    21:21  MediaWiki:Pagetitle‎ (diff | hist) . . (+16). . Yar (talk | contribs) (idk if this will help or hurt)
N    21:18  MediaWiki:Aboutsite‎ (diff | hist) . . (+17). . Yar (talk | contribs) (one less thing to parse)
</wikionly>

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