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Revision as of 10:26, 8 May 2007
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.
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, 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.
Physiological control of metabolic balance
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.
This work is preliminary but is very exciting - we hope to be able to say more soon!
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