Doctoral Researchers

 
Engert, Nicole

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JSMC Fellow

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Research Group
Microbial Immunology
PhD Project:

Mechanisms of Candida albicans colonization and translocation

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Abstract: The opportunistic fungal pathogen Candida albicans is a common member of the normal microbiota of humans colonizing mucosal surfaces, especially the gastrointestinal tract. However, as...
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... an opportunistic pathogen, C. albicans can disseminate from the intestine and cause disseminated life-threatening diseases if the gastrointestinal balance is disturbed, e. g. by antibiotic treatment, disruption of epithelial barrier function or immunosuppression. One predisposing factor for disseminated candidiasis is major surgery. During prolonged surgery, general anesthesia induces centralization of blood flow, leading to mesenteric ischemia. Mesenteric ischemia results in local hypoxia of intestinal epithelia which leads to a damaged gastrointestinal barrier. We therefore hypothesize that mesenteric ischemia and intestinal hypoxia enhances translocation of C. albicans through the epithelial barrier and thereby contributes to the development of disseminated candidiasis. Thus, the aim of this project is to characterize the interaction of C. albicans with intestinal epithelial cells under normoxic and hypoxic conditions and to identify fungal factors important for translocation under hypoxia. Differential staining and microscopy, damage and viability assays will be performed in monolayer and trans-well assays to determine the translocation potential of C. albicans during normoxia and hypoxia. To elucidate the influence of hypoxia on the expression of fungal virulence-associated genes, microarray technologies will be used. The role of genes upregulated under hypoxia will be further analyzed using defined fungal knock out and overexpression mutants. To address the host response to C. albicans infection, transcriptional profiling and cytokine analysis will be used. Hypotheses derived from these in vitro experiments will then be tested using murine ex vivo and in vivo models. The results obtained in this project will provide insights into the molecular mechanisms of the translocation of C. albicans through intestinal barriers. This knowledge could provide the basis for the development of novel prophylactic and therapeutic strategies and might reveal potential biomarkers for risk assessment and early diagnosis.
 
 
Esken, Jens

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ILRS Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Dep. Applied and Ecological Microbiology
PhD Project:

Induction of tetrachloroethene respiration in Sulfurospirillum multivorans

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Abstract: Dehalogenation processes driven by natural microbial communities contribute significantly to the global halogen cycle. Such microbial networks include organohalide-respiring bacteria,...
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... which couple the reductive dechlorination or debromination of halogenated organic compounds to energy conservation via a chemiosmotic mechanism. The key enzyme in organohalide respiration is the reductive dehalogenase (RDase), which serves as a terminal reductase. The RDases are iron-sulfur proteins that harbor a corrinoid cofactor at the active site. Organohalide respiration was studied in detail in the tetrachloroethene (PCE)-dechlorinating epsilonproteobacterium Sulfurospirillum multivorans. The organism displays an unusual type of long-term down-regulation of the PCE reductive dehalogenase gene (pceA) expression in the absence of PCE. In close proximity to pceA, open reading frames encoding putative regulatory proteins were identified. The ILRS project aims to determine the role the corrinoid cofactor of the RDase in the long-term regulation of PCE respiration. In addition, the project focuses on the characterization of two-component regulatory systems within the organohalide respiration gene region in S. multivorans and on the molecular mechanism of PCE sensing.