Doctoral Researchers

 
Irmscher, Sarah

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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:
Infection Biology
Friedrich Schiller University Jena
Institute of Nutrition
PhD Project:

Analysis of the molecular interaction of the human pathogenic fungus Candida albicans with macrophages

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Abstract: The human pathogenic yeast Candida albicans escapes the immune response of the human host via different immune evasion strategies. C. albicans induces the adaptive as well as the innate...
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... immune system of the host including formation of antimicrobial peptides, attack by phagocytic cells, and complement activation. C.albicans activates all three complement pathways: the classical pathway by antibodies bound to C.albicans surface structures, the alternative pathway spontaneously, and the lectin pathway by mannan-specific lectins on the pathogen surface. As a consequence activated complement protein C3b binds to the pathogen’s surface, thus directing its opsonization and phagocytosis by recruited macrophages. For evading the complement system C. albicans recruits soluble host complement regulators to its surface, such as factor H and FHL1 as regulators of the alternative pathway, and C4b-binding protein, an inhibitor of the classical and the lectin pathway. Bound to the pathogen’s surface these recruited host regulators mediate inactivation of the central complement component C3. However, the molecular components involved in the evasion of C. albicans and the modulatory effects, which are mediated by fungal proteins via complement receptors on immune cells, particularly monocytes and macrophages, are still poorly understood. The project aims at elucidating the molecular principles of the interaction of C. albicans with macrophages and their response to the pathogen. Thereby the reaction of the immune cells to different stimuli provided by the pathogen will be of particular interest.
 
 
Ivanova, Lia

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ILRS Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
PhD Project:

The impact of redox regulation on the stress response of Aspergillus fumigatus and its role in host-pathogen interaction

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Abstract: Recent studies have shown that reactive oxygen species (ROS), besides their involvement in protein and cell damage, also act as regulators for important cellular functions, mainly...
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... through reversible cysteine oxidation. Previously our group has shown (manuscript in preparation), that A. fumigatus experiences high levels of intracellular oxidative stress during adaptation to hypoxia or antifungal agents. It still remains unclear how ROS are distributed within the cell during these stress conditions and the physiological processes influenced by cysteine oxidation are not yet identified. The project will aim to establish genetically encoded fluorescent redox sensors, on the basis of molecules like HyPer-2 and roGFP2/Grx1-roGFP2, to allow observation of the flow and quantification of intracellular ROS under different stress conditions. Additionally, a quantitative redox proteomics method will be established in order to improve the identification and characterization of oxidative post translational modifications (PTMs). Combining the established iodoTMT method with the iTRAQ approach would also allow measuring changes in overall protein turnover. Later on, the main aim will be to observe intracellular redox changes in A. fumigatus during in vitro interaction with immune cells, allowing us to draw conclusions about the role of redox regulation in host-pathogen interactions.