Doctoral Researchers

 
Kämmer, Philipp

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JSMC Fellow

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

Infection-associated genes of Candida glabrata

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Abstract: Candida glabrata is a commensal of humans which readily colonizes mucosal surfaces like in the gastrointestinal tract. In healthy individuals, these yeasts exist as a harmless part of...
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... the normal microbial flora. However, C. glabrata is also a successful opportunistic pathogen, which can cause infections ranging from superficial mucosal to disseminated via the blood stream, causing severe diseases with a high mortality rate. In terms of oral, vaginal and uri-nary tract infections, C. glabrata has emerged as the second most frequent fungal species after C. albicans. Despite its generic name of Candida, C. glabrata is phylogenetically more closely related to the harmless baker’s yeast Saccharomyces cerevisiae than to other pathogenic Candida species. Additionally, the strategies of C. glabrata to evade and escape the human immune system differ in fundamental aspects from C. albicans. The virulence of C. glabrata is there-fore most likely based on genetic factors which are modified for pathogenic characteristics or which are not found in S. cerevisiae and C. albicans at all. Although the genome sequence of C. glabrata is available, the function of many genes and their role in pathogenicity are still unknown. To identify infection-associated genes of C. glabrata, we use transcription data obtained under infection-simulating conditions and ana-lyze genes which we found to be C. glabrata-specific in silico. The combination of these two methods will define genes which are infection-associated and at the same time specific for C. glabrata. These candidate genes will be analyzed in more detail using established in vitro and in vivo methods to define their biological role.
 
 
Klapper, Martin

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ILRS Student

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

The Roles of Secondary Metabolites in Dictyostelium discoideum – Bacteria Interactions

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Abstract: This project will focus on both the identification of novel natural products as well as on the elucidation of their roles in eukaryote-prokaryote interactions. The social soil amoeba...
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... Dictyostelium discoideum will serve as the model eukaryote, whose secondary metabolome will be explored in a systematic fashion. D. discoideum is a voracious and ubiquitous predator of bacteria causing the depletion of large bacterial reservoirs. This puts both organisms under strong evolutionary selection pressure: consequently, the bacteria have evolved mechanisms to prevent grazing, and the amoeba must counteract or surmount these mechanisms in order to survive, for instance by the secretion of antibacterial metabolites. In particular, we are interested in a group of small molecules known as polyketides, of which only very few have been investigated. The structures and physiological roles of most of them, however, remain unknown. Specifically, we will examine their roles as signals or defense weapons in interspecies interactions when in contact with amoeba-pathogenic soil bacteria using a toolset of bioassays and methods that have been established in our lab. Emphasis will be put on the design of conditions that enable the expression of otherwise silent biosynthetic gene clusters of both the amoeba and bacteria. Thus, secondary metabolites will be accessible that would otherwise not be produced under standard laboratory conditions. Subsequent bioassay-guided fractionation of bioactive extracts from amoebal or bacterial cultures eventually allows for identification of natural products that orchestrate the coexistence and chemical warfare of the competitors in nature through their antibacterial, amoebicidal or cytotoxic properties. Thus, this project may give rise to new leads for anti-infective or anticancer drugs.
 
 
König, Stefanie

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Pharmacy
Dep. of Pharmaceutical / Medicinal Chemistry
PhD Project:

Mode of action and target identification of fungal secondary metabolites

 
 
König (neé Franke), Annika

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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.
 
 
Krauße, Thomas

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ChemBioSys Student

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Microbiology
Microbial Communication
 
 
Krespach, Mario

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JSMC Fellow

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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:

Communication between Streptomyces iranensis and Aspergillus – the streptomycete´s inducing principle?

 
 
Kreuzenbeck, Nina

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ChemBioSys Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Chemical Biology of Microbe-Host Interactions
PhD Project:

Isolation, characterization and functional analysis of novel biomolecules from the mutualistic food fungus of fungus-growing termites

 
 
Kruse, Stefan

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JSMC Fellow

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

Syntrophy in co-cultures with Sulfurospirillum multivorans: Bidirectional interspecies hydrogen transfer in the energy metabolism

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Abstract: Many bacterial species living in microbial communities interact with each other through the exchange of metabolic products. In anoxic environments, hydrogen is an important metabolite...
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... that is transferred from a hydrogen producing fermentative organism to a hydrogen consuming microorganism. The interspecies hydrogen transfer is the most abundant form of syntrophy under anaerobic conditions. It is usually very important for both syntrophy partners. Hydrogen production by fermentative bacteria and hydrogen oxidation by organisms using this metabolite as electron donor are catalyzed by enzymes designated hydrogenases [1]. The organohalide-respiring epsilonproteobacterium Sulfurospirillum multivorans [2] produces hydrogen when grown on fermentable substrates in the absence of organohalides and utilizes hydrogen as electron donor in the presence of tetrachloroethene as electron acceptor for energy conservation via organohalide respiration. This indicates that the organism may act as a syntrophy partner in both functions, namely hydrogen production and hydrogen consumption. Little is known so far about syntrophy with epsilonproteobacteria, despite their high abundance in a variety of ecosystems, which was discovered recently. S. multivorans harbors genes coding for four different hydrogenases, two putative hydrogen-oxidizing enzymes (MBH, Hup) and another two possibly involved in hydrogen production (Ech, Hyf) [3]. The project will focus on the possible role of S. multivorans in syntrophic associations as a hydrogen producer or a hydrogen consumer and on the physiological function of the hydrogenases. Cocultures will be established on the one hand with a typical hydrogen producer (i.e. a fermenting bacterium) for example with lactate as electron donor and on the other hand with obligate hydrogen oxidizers such as methanogens or obligate organohalide-respiring bacteria (OHRB) [4]. The latter coculture would considerably extend our knowledge on the substrate spectrum with respect to the electron donors that may be utilized for reductive dechlorination in environments contaminated with organohalides. This coculture may even be able to completely dechlorinate compounds that cannot be dechlorinated by only one of the syntrophy partners (e. g. tetrachloroethene to ethene) [5]. The hydrogenases of S. multivorans, especially the uptake hydrogenases, will be purified and kinetically characterized.
 
 
Kuhlisch, Constanze

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute for Inorganic and Analytical Chemistry
PhD Project:

Signals and metabolic changes causing phenotypic plasticity in phytoplankton

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Abstract: The project will address the hypothesis that morphological changes in unicellular pyhtoplankton resulting in colony formation follow a substantial metabolic reprogramming of the cells,...
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... which, in turn, is under the control of multiple external stimuli. Studies will apply mass spectrometry based metabolomic methods, structure elucidation of the metabolites involved in aggregation, microscopic analysis, and in situ mesocosm and shipboard experiments. The project will focus on two major model species, Phaeocystis sp. and Skeletonema marinoi and will be conducted within an international collaborative network. Unicellular algae of the phytoplankton can respond to the presence of herbivores and conspecifics by the formation of colonies or chains. The effects of this variability can be considerable since sinking velocity, nutrient uptake and also palatability to specific herbivores is strongly dependent on the size of the free floating organism in the water. Phaeocystis sp., that often contribute substantially to the phytoplankton biomass of the oceans, can form solitary cells of 4-6 µm and colonies that can reach up to 30.000µm in diameter dependent on the presence of specific herbivores (Long et al. 2007). In diatoms like Skeletonema marinoi switches from unicellular growth to chain formation can be observed that are apparently also under the control of external stimuli. While these processes are quite well understood in terms of their effects on nutrient uptake, feeding processes, and plankton dynamics, the underlying regulative principles and physiological changes are still poorly understood (Serizaqa et al. 2008; Tang et al. 2008). In this project the hypothesis is addressed that such changes in morphology go ahead with a substantial metabolic reprogramming of the cells, which is under the control of multiple external stimuli including signals from herbivores and conspecifics. In Phaeocystis colony formation is apparently dependent on mucus formation by excretion of polysaccharides (van Rijssel et al. 2000) while diatoms rely on altered cell morphology for chain formation. Studies in this project will focus on two major model species starting with an investigation of induced exudate formation of Phaeocystis sp. and extending the research to the diatom Skeletonema costatum. Both algae are grown and manipulated in the lab under standard culture conditions. Mass spectrometry based chemical profiling of extra- and intracellular metabolites related to unicellular or colonial cell stage will reveal major differences within the algal metabolome. Signals released by herbivores that are known to promote or inhibit cell aggregate formation (Long et al. 2007) will allow to regulate metabolic pathways. Further structure elucidation of characteristic metabolites will be based on high-resolution mass spectrometry and large scale purification/NMR. Moreover collaboration with the University of Bergen enables the monitoring for chemical signal production during fjord mesocosm experiments and during an anticipated cruise to the Barents Sea. Thereby, metabolic events can be correlated to growth stage, colony formation and predation. Relevant compounds could be identified, purified and used for further bioassays. Skeletonema marinoi will be investigated in a similar way.
 
 
Kurth, Colette

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ChemBioSys Student

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Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
Junior Research Group
Secondary Metabolism of Predatory Bacteria
PhD Project:

Photoresponsive Modulation of a Freshwater Phytoplankton Community

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Abstract: Small molecule-mediated interactions of freshwater organisms are barely investigated with respect to their ecological impacts. In this project, the role of siderophores in structuring...
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... planktonic communities will be analyzed. Recent evidence suggests that some freshwater bacteria have acquired pathways for the biosynthesis of photoreactive Fe(III) ligands. Such compounds were before only known from marine bacteria, and they had been linked to the redox cycling of iron in the oceans. When exposed to sunlight, the iron complexes of these siderophores rapidly undergo an oxidative decomposition. At the same time, the coordinated ferric iron is reduced via ligand-to-metal charge transfer. The temporary increase of the Fe(II) concentration in the vicinity of the siderophore-producing bacteria promotes the assimilation of iron by associated algae. These planktonic consortia include many phototrophs, which are themselves not capable of siderophore-mediated iron uptake, but require large amounts of transient metal to support the fixation of carbon. Even though preliminary studies confirmed the growth-stimulating effects of photoreactive siderophores on marine microalgae and fueled the idea of a “carbon-for-iron” paradigm that would also be advantageous for the bacterial producers, many aspects of this mutualistic interaction are still poorly understood. In particular, we plan to resolve the discriminatory effects of photoreactive siderophores on a heterogeneous plankton community. Its members include both siderophore producers, such as cyanobacteria, and non-producers, among them many eukaryotic algae and protists. While the latter groups likely benefit from a facilitated access to iron, the former might encounter the opposite situation as they forfeit their advantage of endogeneous siderophore biosynthesis. It is therefore assumed that the bacterial release of photoreactive Fe(III) ligands induces a shift in the composition of a planktonic consortium away from prokaryotic siderophore producers. We will assess this impact, which may help us to delineate new strategies for the biological control of harmful algal blooms in rivers and lakes. Furthermore, we set out to clarify whether bacterial siderophore biosynthesis responds to signals from eukaryotic microalgae. The concomitant communication could rely on chemical molecules or, alternatively, on direct physical contact between the partners. Both scenarios will be probed by determining levels of bacterial gene expression in the presence and absence of diatoms or their cell culture extracts. We expect this experiment to provide fundamental insights into the evolution of natural product-mediated trans-kingdom interactions. Finally, we will validate the generalizability of mutualsitic iron sharing between heterotrophic bacteria and diatoms. For this purpose, we will analyze the genome sequences from selected freshwater bacteria, exploiting the predictability of microbial siderophore biosynthesis. The products of cryptic pathways will be isolated and characterized.