A2 Cyclic nucleotide signaling and metabolic regulation during asexual development of the obligate intracellular parasite Toxoplasma gondii (Gupta)

Research Group: Metabolism and interactions between parasites and hosts
Address: Humboldt-Universität zu Berlin, Department of Biology, Molecular Parasitology, Philippstr. 13, House 14, 10115 Berlin
Supervisor: Nishith Gupta, PhD
Doctoral Researcher: Laura Radtke

Project Description

T. gondii is an obligate intracellular parasite that is capable of infecting nearly all vertebrates. Successful infection, pathogenesis and transmission of the parasite depend on multiplication, persistence and interconversion of its two asexual stages. The fast-replicating tachyzoites cause acute tissue necrosis and then differentiate into dormant, tissue-dwelling bradyzoite (chronic) stage upon physicochemical and immune stress. Cyclic nucleotides are known to mediate the adaptive gene expression and metabolic reprogramming associated with stress response in a number of microbial pathogens. Likewise, cyclic nucleotides are expected to control acute-chronic stage differentiation and cognate modulation of metabolism in T. gondii. Our work has extensively characterized the carbon metabolism and membrane biogenesis in tachyzoites, which undergo a substantial biomass synthesis to sustain their rapid lytic cycle. We have also generated transgenic T. gondii lines expressing a photo-activated adenylate cyclase, which allows specific and spatiotemporal induction of cAMP in response to blue light and enables conversion of tachyzoites into bradyzoites. Such an optogenetic parasite strain offers a valuable tool to interlink cAMP-mediated signaling with stage-specific reprograming of parasite metabolism. The project uses a combination of classical and contemporary tools including parasite culture, genetic manipulation, fluorescence microscopy, enzyme assays, isotope labeling and optogenetics to discover and establish the physiological significance of cAMP signaling in governing the metabolism of T. gondii. We are seeking a highly motivated PhD student with an educational background in biology, biochemistry and/or bioinformatics. For additional information about our ongoing research and laboratory, please refer to https://www.parasit.hu-berlin.de/gruppenseiten-en/molpara-en/research/metabolism

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