Dionne

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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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15 April 2024

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Upload log Xning098 talk contribs uploaded File:Figure 1 electroosmotic flow.png ‎

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The paper that launched microfluidics - Xi Ning‎ diffhist +1,702‎ Xning098 talk contribs

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			18:49		Cells and Nanoparticles in Flow - Namish Kokkula‎‎ 2 changes history +6,131‎ [Nkokkula‎ (2×)]
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					18:48 Nkokkula talk contribs uploaded File:MarginationSize.jpeg ‎(Reprinted with permission from Namdee, K.; Thompson, A. J.; Charoenphol, P.; Eniola-Adefeso, O. Margination Propensity of Vascular-Targeted Spheres from Blood Flow in a Microfluidic Model of Human Microvessels. Langmuir 2013, 29 (8), 2530–2535. https://doi.org/10.1021/la304746p. Copyright 2013 American Chemical Society.)
					18:34 Nmhatre talk contribs uploaded File:NonlinearGradientDevice VaryingHorizontalChannelWidth.jpg ‎(Device made by Abe et al. which creates a nonlinear gradient by varying the horizonatal channel widths. "Reprinted with permission from Abe, Y., Kamiya, K., Osaki, T., Sasaki, H., Kawano, R., Mikia, N., Takeuchi, S. Nonlinear concentration gradients regulated by the width of channels for observation of half maximal inhibitory concentration (IC50) of transporter protein. Royal Society of Chemistry. 2015,140. DOI: https://doi.org/10.1039/C4AN02201G. Copyright 2015Royal Society of Chemistry.")
					18:17 Nmhatre talk contribs uploaded File:NonlinearGradientDevice.jpg ‎(A nonlinear gradient device created Selemovic et al. "Reprinted with permission from Šeila Selimović, Woo Young Sim, Sang Bok Kim, Yun Ho Jang, Won Gu Lee, Masoud Khabiry, Hojae Bae, Sachin Jambovane, Jong Wook Hong, and Ali Khademhosseini Analytical Chemistry 2011 83 (6), 2020-2028 DOI: 10.1021/ac2001737 . Copyright 2011 American Chemical Society.")
					18:12 Nmhatre talk contribs uploaded File:NonlinearGradientDevice.webp ‎(A nonlinear gradient device created Selemovic et al. "Reprinted with permission from Šeila Selimović, Woo Young Sim, Sang Bok Kim, Yun Ho Jang, Won Gu Lee, Masoud Khabiry, Hojae Bae, Sachin Jambovane, Jong Wook Hong, and Ali Khademhosseini Analytical Chemistry 2011 83 (6), 2020-2028 DOI: 10.1021/ac2001737 . Copyright 2011 American Chemical Society.")

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