Doctoral Researchers

 
Raguž, Luka

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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:

Molecular synthetic approaches towards natural sphingoid base-type signaling molecules

Abstract: Sphingoid bases and sphingolipids are essential multifunctional cellular compounds, which serve not only as integral components of cell membranes, but also as essential regulatory...
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... signals for fundamental cellular processes. They were first thought to exist exclusively in eukaryotes, but have now been repeatedly identified and isolated from important bacterial and viral sources. Despite being abundant signaling molecules, the biological function of many sphingolipid derivatives remains elusive. Prominent examples of fungal origin are sphingofungins and myriocin (ISP-1), which exhibit antifungal activity in the picomolar to nanomolar range. Their discovery has led to the development of many pharmaceutical drug leads (e.g. FTY720 and safingol. But the intrinsic biological role of sphingofungins is unknown until to date. In another study bacterial sulfonolipids, such as RIF-1 and RIF-2, regulate an onset of development in one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. A structural analog IOR-1 inhibits partially the activity of RIF molecules. Due to their intrinsic biological function of these types of molecules, this research project will focus on efficient and new synthetic strategies towards of rare microbial sphingoid base-type signaling molecules to allow their detailed functional analysis.
 
 
Ramachandra, Shruthi

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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. Microbial Pathogenicity Mechanisms
PhD Project:

Host pathogen interactions of human-pathogenic yeast

 
 
Raszkowski, Daniel

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JSMC Fellow

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Institute/Dep.
Friedrich Schiller University Jena
Institute of Pharmacy
Pharmaceutical Biology I
PhD Project:

Evolution of glorin-based intercellular communication in social amoebae

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Abstract: The “social amoebae” are a group of unicellular organisms that transiently achieve multicellularity by aggregation of single cells, aimed at the formation of fruiting bodies whose...
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... spores survive environmental conditions unfavorable for growth. Multicellular development of social amoebae is accompanied by intensive intercellular communication, which has to some extent interesting parallels with bacterial quorum-sensing and quorum-quenching systems. Extracellular signaling molecules used by social amoebae to coordinate aggregation of usually reffered to “acrasins” irrespective of their chemical natures. A hallmark or amoebal acrasin systems is that the signaling molecule is periodically degraded, which allows the amoebae to position in an acrasin gradient and move to the highest concentration of the signaling molecule, which is the aggregation center. Thus, besides the signaling molecule and its receptor, an acrasin system of social amoebae requires a self-produced and secreted enzyme that inactivates the acrasin. Several of the species that diverged late in the evolution of social amoebae use cAMP to regulate aggregation. In this project we follow the hypothesis, based on our previous work, that the phylogenetically oldest species of social amoebae use the modified dipeptide glorin instead of cAMP as the intercellular signaling molecule that coordinates aggregation. In addition, we assume that glorin is secreted by cells of genus Polysphondylium and that these species produce an enzyme (a “glorinase”) that is capable of inactivating glorin in the extracellular space. A major goal of this project is to identify the glorinase-encoding gene from Polysphondylium pallidum. To this end, we will establish a biochemical assay to measure glorinase activity in the buffer supernatant of aggregating P. pallidum cells. This assay will be fundamental to purify extracellular glorinase from aggregating P. pallidum cells by activity-guided fractionation. The glorinase protein will be identified by means of proteomic methods and this information will be used to identify the glorinase gene in the P. pallidum reference genome. To explore the function of glorinase in coordinating P. pallidum aggregation, we will generate a knock-out mutant of glorinase in P. pallidum. This mutant will be characterized in terms of developmental phenotypes. A detailed expression of the glorinase gene will answer the question how the gene is regulated at the transition from growth to development of P. pallidum cells. Search for functional glorinase orthologs in other sequenced genomes of social amoebae will shed light on the evolution of the glorin-based communication system in social amoebae as well as on the origin of ths system and its relation to bacterial quorum-sensing systems.
 
 
Rischer, Maja

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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
Chemical Biology of Microbe-Host Interactions
PhD Project:

Exploring the chemical potential and mechanisms of marine microbe-invertebrate interactions

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Abstract: Metamorphosis in marine invertebrate larvae is often an environmentally dependent process and larvae of many marine invertebrates use biofilm components as cues to appropriate...
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... settlement sites (habitats). In many phyla species of the bacterial genus Pseudoalteromonas induce larval settlement and metamorphosis, but despite century long intensive research, we still know very little about the bacterial ligands that stimulate larval settlement and the cellular basis of their detection by larvae.
We have chosen the colonial marine hydroid Hydractinia echinata as model organism, which grows on the shells inhabited by hermit crabs. Here, it is long known that the metamorphosis from free-swimming larvae to the sessile polyp is particularly stimulated by bacteria of the genus Pseudoalteromonas. This project will first focus on the characterization of the specific bacterial morphogenic factor from a highly inductive Pseudoalteromonas strain using a combination of various methods (molecular biology, genome analysis, proteomics, and imaging).
Biofilm and invertebrate settlement are part of the so-called ‘biofouling community’ that inhabit artificial surfaces and cause major economic losses around the globe. Analysing the settlement mechanisms might lead to new strategies to prevent biofouling, and decrease the current use of environmentally harmful and toxic antifouling agents.
As a second project we will analyse the chemical potential of microbes associated with H. echinata. It is known that Cnidara cultures are sensible to infection and parasitic infestation when they have lost important microbial commensals and symbionts. We hypothesize that microbial commensals contribute by secretion of antimicrobial compounds to the host defense and therefore represent a very promising source of biologically important natural products. We have established a collection of wildtype bacteria and fungi from the tissue surface of healthy polyps, which are currently under investigation using bioassay-guided fractionation and other dereplication methods. Isolation and structure identification of antimicrobial secondary metabolites is performed by using different analytical techniques like HPLC, NMR, UV-VIS and others. Based on sequenced genomes we want to investigate biosynthetic pathways of the characterized molecules and predict unknown secondary metabolite clusters through genome mining.
 
 
Röcker, Marie

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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:

Identification of immunogenic components of Aspergillus fumigatus for vaccine development

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Abstract: Aspergillus fumigatus is the most important air-borne fungal pathogen. In recent years, it became evident that certain unknown components of A. fumigatus apparently lead to protection...
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... against invasive aspergillosis in a mouse infection model. Until now, it remains to be shown whether the protection is due to a B cell response or rather T cell response. Furthermore, the components of A. fumigatus triggering this response have not been identified. The proposed project will investigate, which morphotypes (spore, mycelium) promote an immune response and which protein antigens contribute to this host reaction. The immunological properties of selected protein antigens will be further investigated in murine models of Invasive Aspergillosis (B-cells, T-cells). In collaboration with the Charite´ (Berlin) the T-cell response against Invasive Aspergillosis of Cystic Fibrosis patients will be characterized.
 
 
Rudolphi, Sven

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FungiNet Student

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

Host-pathogen interactions during Candida albicans translocation through the gut