Date: 17.7.2015
Multicellular organisms are made up of many specialized cells performing different functions. The cells differ dramatically by their energy requirements as well as their ability to store excess energy.
Homeostatic regulation of energy balance is tightly connected to cell growth and involves a signaling nexus of AMPK and TOR, which is highly conserved in evolution. Research in our laboratory investigates mechanisms underlying the paracrine signals of metabolic imbalance within tissues and coordination of tissue activity. We focus our study on Drosophila signaling by extracellular adenosine and by chitinase-like proteins (called in flies the Imaginal disc growth factors, IDGFs), which have prominent roles on cell growth and AMPK and TOR activity.
We optimize the procedures allowing generation of insect mutants and perform phenotypic analysis of key genes involved in energy homeostasis. We also develop approaches for the investigation of extrinsic control of tissue growth by using clonal analysis in Drosophila imaginal discs as well as in imaginal disc cells in vitro of as model systems.
We isolated Drosophila mutants in most genes involved in adenosine and IDGF signaling and analyzed their phenotypes. We also characterized adenosine receptor ligand profile and characterized its effect on cell growth as well as on neural tissue. We found that adenosine-regulated energy homeostasis has a crucial role on the survival of mosaic neoplastic epithelial outgrowths, while the growth of control mosaic clones is not affected. In addition, we showed that the IDGFs play important roles in organismal defense.
Thanks to the Modbiolin project we were able to use the inverted microscope OLYMPUS IX73P2F and perform the cell viability screening of Drosophila cells using RNAi inactivation of multiple candidate genes. The laboratory is financed by a grant from the Grant Agency of the Czech Republic
Author: prof. RNDr. Michal Žurovec CSc.
We acknowledge the use of research infrastructure that has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 316304.
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Sajwan Suresh, Sidorov Roman, Stašková Tereza, Žaloudíková Anna, Takasu Yoko, Kodrík Dalibor, Žurovec Michal (2015) Targeted mutagenesis and functional analysis of adipokinetic hormone-encoding gene in Drosophila Insect. Biochemistry and Molecular Biology 61: 79-86.
Sidorov R., Kucerova L., Kiss I., Zurovec M. (2015) Mutation in the Drosophila melanogaster adenosine receptor gene selectively decreases the mosaic hyperplastic epithelial outgrowth rates in wts or dco heterozygous flies. Purinergic Signalling 11: 95-105.
Takasu Y, Tamura T, Sajwan S, Kobayashi I, Zurovec M (2014) The use of TALENs for nonhomologous end joining mutagenesis in silkworm and fruitfly. Methods 69: 46-57.
Kucerova L., Broz V., Fleischmannova J., Santruckova J., Sidorov R., Dolezal V., Zurovec M., (2012) Characterization of the Drosophila adenosine receptor: the effect of adenosine analogs on cAMP signaling in Drosophila cells and their utility for in vivo experiments. Journal of Neurochemistry 121: 383-395.
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