@phdthesis{Jueppner2014,
  author    = {J{\"u}ppner, Jessica},
  title     = {Characterization of metabolomic dynamics in synchronized Chlamydomonas reinhardtii cell cultures and the impact of TOR inhibition on cell cycle, proliferation and growth},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-76923},
  school      = {Universit{\"a}t Potsdam},
  pages     = {VI, 153},
  year      = {2014},
  abstract  = {The adaptation of cell growth and proliferation to environmental changes is essential for the surviving of biological systems. The evolutionary conserved Ser/Thr protein kinase "Target of Rapamycin" (TOR) has emerged as a major signaling node that integrates the sensing of numerous growth signals to the coordinated regulation of cellular metabolism and growth. Although the TOR signaling pathway has been widely studied in heterotrophic organisms, the research on TOR in photosynthetic eukaryotes has been hampered by the reported land plant resistance to rapamycin. Thus, the finding that Chlamydomonas reinhardtii is sensitive to rapamycin, establish this unicellular green alga as a useful model system to investigate TOR signaling in photosynthetic eukaryotes. The observation that rapamycin does not fully arrest Chlamydomonas growth, which is different from observations made in other organisms, prompted us to investigate the regulatory function of TOR in Chlamydomonas in context of the cell cycle. Therefore, a growth system that allowed synchronously growth under widely unperturbed cultivation in a fermenter system was set up and the synchronized cells were characterized in detail. In a highly resolved kinetic study, the synchronized cells were analyzed for their changes in cytological parameters as cell number and size distribution and their starch content. Furthermore, we applied mass spectrometric analysis for profiling of primary and lipid metabolism. This system was then used to analyze the response dynamics of the Chlamydomonas metabolome and lipidome to TOR-inhibition by rapamycin The results show that TOR inhibition reduces cell growth, delays cell division and daughter cell release and results in a 50\% reduced cell number at the end of the cell cycle. Consistent with the growth phenotype we observed strong changes in carbon and nitrogen partitioning in the direction of rapid conversion into carbon and nitrogen storage through an accumulation of starch, triacylglycerol and arginine. Interestingly, it seems that the conversion of carbon into triacylglycerol occurred faster than into starch after TOR inhibition, which may indicate a more dominant role of TOR in the regulation of TAG biosynthesis than in the regulation of starch. This study clearly shows, for the first time, a complex picture of metabolic and lipidomic dynamically changes during the cell cycle of Chlamydomonas reinhardtii and furthermore reveals a complex regulation and adjustment of metabolite pools and lipid composition in response to TOR inhibition.},
  language  = {en}
}
@misc{MeyerMatissekMuelleretal.2014,
  author    = {Meyer, S{\"o}ren and Matissek, M. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {In vitro toxicological characterisation of three arsenic-containing hydrocarbons},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-74201},
  pages     = {1023 -- 1033},
  year      = {2014},
  abstract  = {Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.},
  language  = {en}
}
@article{MeyerMatissekMuelleretal.2014,
  author    = {Meyer, S{\"o}ren and Matissek, M. and M{\"u}ller, Sandra Marie and Taleshi, M. S. and Ebert, Franziska and Francesconi, Kevin A. and Schwerdtle, Tanja},
  title     = {In vitro toxicological characterisation of three arsenic-containing hydrocarbons},
  series = {Metallomics},
  volume    = {2014},
  journal   = {Metallomics},
  number    = {6},
  issn      = {1756-591X},
  doi       = {10.1039/c4mt00061g},
  pages     = {1023 -- 1033},
  year      = {2014},
  abstract  = {Arsenic-containing hydrocarbons are one group of fat-soluble organic arsenic compounds (arsenolipids) found in marine fish and other seafood. A risk assessment of arsenolipids is urgently needed, but has not been possible because of the total lack of toxicological data. In this study the cellular toxicity of three arsenic-containing hydrocarbons was investigated in cultured human bladder (UROtsa) and liver (HepG2) cells. Cytotoxicity of the arsenic-containing hydrocarbons was comparable to that of arsenite, which was applied as the toxic reference arsenical. A large cellular accumulation of arsenic, as measured by ICP-MS/MS, was observed after incubation of both cell lines with the arsenolipids. Moreover, the toxic mode of action shown by the three arsenic-containing hydrocarbons seemed to differ from that observed for arsenite. Evidence suggests that the high cytotoxic potential of the lipophilic arsenicals results from a decrease in the cellular energy level. This first in vitro based risk assessment cannot exclude a risk to human health related to the presence of arsenolipids in seafood, and indicates the urgent need for further toxicity studies in experimental animals to fully assess this possible risk.},
  language  = {en}
}