Doctoral Researchers

 
Ferreira Gomes, Marta

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Center for Molecular Biomedicine
Laboratory of Cell Biology
PhD Project:

B cells and antibodies in protective immunity to Candida albicans infection

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Abstract: Candida albicans colonizes mucosal surfaces of most healthy individuals as a benign member of the human microbiota, but may become an invasive pathogen in the immunocompromized host. In...
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... the clinical setting, C. albicans is a major cause of nosocomial infections and may cause severe bloodstream invasion with mortality rates exceeding those of bacterial sepsis. Basic immunological principles that allow tolerance to this commensal on the one hand but mediate antifungal immunity on the other hand are thus investigated, with the final goal to elicit protective immune responses against this opportunistic pathogen in the human host. While in the context of acute bloodstream infection innate immune responses appear to predominate protection, adaptive immunity is required for long term immunological memory and immunization. In the gut, the major reservoir of C. albicans, the fungus may persist even though it evokes a response from both T and B lymphocytes. The present project will focus on the role of antibodies produced by B cells in the maintenance of benign C. albicans colonization, as well as in protection of individuals from secondary challenges with C. albicans bloodstream infections, to approach the question whether and how a protective antibody response to C. albicans can be triggered in humans.
 
 
Ferreira Lobo da Graça, Ana Patrícia

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

Biosynthesis and function of the cryptic cofactor mycofactocin

 
 
Flak, Michal

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Molecular and Applied Microbiology
 
 
Förster, Toni

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FungiNet Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Microbial Pathogenicity Mechanisms
PhD Project:

Identification and characterisation of translocation-associated factors of Candida albicans

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Abstract: Candida albicans is normally a harmless commensal inhabitant of mucosal surfaces, such as the human gut, but is also an opportunistic pathogen. Under certain predisposing conditions, C....
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... albicans can cause life-threatening systemic infections. This fungus is the most common cause of life-threatening nosocomial fungal bloodstream infections. By crossing the intestinal barrier, C. albicans can access the bloodstream and can cause lethal sepsis. Therefore, understanding the process of this translocation will be crucial for future therapies. The project is divided into two main parts. The first focus of this project is Ece1. Ece1 is a protein which is proteolytically processed into several short peptides, one of which acts as a pore-forming toxin. Such an activity may be crucial for translocation through host barriers. Detailed analysis of C. albicans mutants, lacking ECE1, during interactions with intestinal cells will be performed to elucidate the importance of this protein in translocation. The second part will focus on the identification of novel fungal factors and attributes required for translocation through intestinal epithelial tissue. A translocation assay for screening C. albicans mutant libraries will be established to identify new genes associated with transmigration through intestinal cells. Modified assays with gut-mimicking conditions (e.g. pH, O2) and a more detailed analysis of these new transmigration-associated genes will be carried out. Additionally, the influence of probiotic bacteria on the pathogenicity and translocation of C. albicans will be investigated. The aim here is the development of a commensal-to-pathogen switch model. The presence of bacteria inhibits the epithelial damaging activity of C. albicans. Therefore, by adding antibiotics to a co infection model of bacteria (e.g. Lactobacillae) and C. albicans, the fungus is predicted to switch to a pathogenic form. This process will be followed by transcriptional profiling of the different states during the switch from commensal to pathogen. By elucidating these different aspects of C. albicans colonisation and transmigration, a better understanding of translocation will be achieved, which may ultimately lead to novel treatment strategies to prevent candidaemia.
 
 
Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Dept. Microbial Pathogenicity Mechanisms
PhD Project:

Characterization of Candida albicans Ece1 membrane integration

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Abstract: Candida albicans is regarded as the most important of all medically relevant yeasts and is an extremely successful pathogen in humans. In contrast to most pathogenic fungi in humans...
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... such as Aspergillus fumigatus, Cryptococcus neoformans, or Histoplasma capsulatum, which are found in the environment, C. albicans belongs to the normal microflora of mucosal surfaces and are regarded as harmless commensals in most circumstances. In fact, most humans are probably colonized with these yeasts. An intact immune system and a balanced microbial flora are normally sufficient to protect the individual from Candida infections. However, certain critical events such as extensive antibacterial treatment or dysfunction of the immune system may enable these fungi to overgrow the microbial flora on mucosal surfaces. Using cellular, microbial, molecular and biochemical methods and C. albicans as model organisms, the goal of our research is to identify factors which fungal pathogens need to cause diseases. In addition to these efforts to increase our understanding of the basics of pathogenesis of fungal infections, we also seek to identify new biomarkers for diagnostic approaches and potential targets for antimycotic drug development. Under certain conditions, C. albicans is able to escape from macrophages by producing hyphal filaments. We discovered that the fungus produces the peptide toxin Ece1 during hyphal formation and during these interactions. We propose that Ece1 integrates into the host membrane to gain access to the host cytoplasm via pore formation. We have already shown that Ece1 plays an essential role during interaction with epithelial cells (unpublished data). In this project, the role of Ece1 integration will be studied in collaboration with groups working on optical high technology.
 
 
Funai, Benjamin

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Combinatorial effects in the heavy metal resistance of streptomycetes

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Abstract: Actinomycetes and especially the genus Streptomyces, have a unique ability to produce a wide range of biologically-active secondary metabolites and play an important role in the...
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... pharmaceutical and chemical industry. Due to the fact, that there has been a decline in the discovery of new metabolites from common soil-dwelling actinomycetes, the screening for new metabolites could be enlarged by extreme habitats like heavy metal contaminated sites which could offer the chance to isolate less common actinomycetes. In these habitats, microbes have to cope with rough conditions such as low pH, high concentrations of heavy metals and salts as well as low nutrient contents and therefore evolved several adaptations like heavy metal resistances and potentially new secondary metabolite pathways. Studies have shown that heavy metal stress and co-cultivation can induce a shift in the secondary metabolites pattern by activating gene clusters which are silent under standard screening conditions. By knowing this, a strain collection of actinomycete isolates originating from a former mining area will be screened for their potential to produce antibiotics and other biologically-active secondary metabolites under heavy metal stress and co-cultivation. The experiments will be carried out with different bacteria and yeast isolates as well as several heavy metals in a microfluidic system which is developed by partners of the project „BactoCat - Neue Syntheseleistungen durch Kopplung mikroorganismischer und Metallnanopartikel-katalysierter Prozesse in der Mikroreaktionstechnik 031A161B”.
 
 
Fürst, David

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
PhD Project:

Influence of microorganisms on the phytoremediation-potential of different plants on heavy-metal contaminated soils