Doctoral Researchers

 
Viediernikova, Iuliia

cv + contact data »

publications »

ILRS Student

Email »

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

The role of virulence determinants of the human pathogenic fungus Aspergillus fumigatus in the defense against fungivorous amoeba.

PDF »

Abstract: Infections with opportunistic pathogens are among the leading causes of morbidity and mortality in humans. The filamentous fungus Aspergillus fumigatus represents a classical example...
more
... foe this group, as it normally thrives as saprophyte in the soil, but disperses asexual conidia as infectious agents. Upon inhalation by immunocompromised host, these conidia can germinate and invade the surrounding tissue. Lethality of such an invasive aspergillosis is high due to limited diagnostic and therapeutic options. A multitude of general virulence factors can lead to invasive growth and rapid disease progression with often enormously high death rates, exceeding even 90% in certain patient cohorts (Brakhage and Langfelderk, 2002). Little is known on the evolutionary origin of this armory. In a recent sturdy we could show that two major virulence determinants, formation of the protective DHN-melanin and the second metabolite gliotoxin are also effective against the soil amoeba Dictyostelium discoideum (Hillmann et al., 2015). An amoeba defensive function was also detectable for trypacidin, a spore born toxin of A. Fumigatus with antiphagocytic properties (Mattern et al., 2015). These results supported the idea some basic mechanisms of fungal virulence could have emerged long before the appearance of innate immune systems and foster the hypothesis that they could be driven from the selection pressure imposed by amoeba predation. A central question of my thesis is therefore if interactions with fungivorous amoeba could have stimulated the development of such virulence mechanisms. To address this point I will exploit an extended model system based on the amoeba Protostelium mycophaga, an obligate fungivore which was isolated from a forest site near Jena. Preliminary results in the group of Falk Hillmann indicate that P. mycophaga has wide food spectrum of ascomycetous or basidiomycetous yeasts, but can also attack fungal hyphae. My work program will analyze the molecular interactions with fungal conidia during phagocytosis, but will include first approaches to analyze the chemical communication between these two antagonistic organisms.
 
 
Vivas, Wolfgang

cv + contact data »

publications »

JSMC Fellow

Email »

Institute/Dep.
Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute-
ZIK Septomics
Research Group Fungal Septomics
PhD Project:

Modulation of Dendritic Cell Function by the fungal Quorum Sensing Molecule Farnesol

PDF »

Abstract: Quorum Sensing is a major mechanism of inter-microbial communication mediated by molecules that are released from growing microorganisms and accumulate in relation to microbial...
more
... replication. Farnesol – the first identified fungal quorum sensing molecule – mediates the response of Candida albicans to growing population density and controls filamentation of C. albicans which is a major virulence trait. Beside species-specific effects on C. albicans, farnesol can exert effects on other microbes and is therefore a prototype mediator of inter- and intraspecies microbial communication. In previous work we have investigated the impact of farnesol on innate immune cells. For this, we used several infection models with primary human monocytes, monocytes-derived dendritic cells, and neutrophilic granulocytes that are established in our lab. Farnesol was able to induce activation of neutrophils and monocytes and triggered the release of pro-inflammatory cytokines. In contrast, farnesol impaired differentiation of monocytes into dendritic cells (DC) by modulating the phenotype, cytokine release and migrational behavior during differentiation. These modulatory effects resulted in severely impaired induction of antifungal activity in DC. In the proposed project, we will build from this work and try to elucidate the molecular basis of farnesol mediated DC differentiation, maturation and functionality. We will use of state of the art microbiological and immunological tools, primarily working with monocytes-derived DC. The project is built on several collaborations, including Prof. Dr. Marc Thilo Figge.
 
 
von Lachner (nee Klippstein), Carolin

cv + contact data »

publications »

JSMC Fellow

Email »

Institute/Dep.
University Hospital Jena
Septomics Research Centre
PhD Project:

The role of E. coli-induced alterations of the Ubiquitin-Proteasome-System (UPS) for the Innate Immune Response and function of the human endothelium

PDF »

Abstract: Sepsis occurs as a result of a complex interaction between the microorganism and the host immune response. There is growing evidence of the pivotal role of the endothelium in the...
more
... pathophysiology of sepsis. Systemic activation of the endothelium is characterized by the secretion of pro-inflammatory cytokines, overexpression of cell adhesion molecules with subsequent recruitment of leukocytes at non-infectious locations (1). Recent data indicate that E. coli is the most frequent pathogen isolated in patients with sepsis that is associated with an increased mortality rate. The Ubiquitin-Proteasome-System (UPS) represents the most important non-lysosomal cellular protein degradation machinery. Its function is tightly connected with the timely degradation of regulatory proteins, the elimination of misfolded proteins to restore cell homeostasis (2). Since this might be an important feature of counteracting endothelial and tissue damage during sepsis, we will investigate the composition of the UPS in endothelial cells following infection with E. coli in vitro and in a knock-out mice model lacking particular components of the UPS. Own work and relevant publications The BMBF funded Host Septomics Research Group is part of the Center for Innovation Competence “Septomics” at the Friedrich-Schiller-University of Jena. Our team analyzes the pathogen-host interactions with a strong focus on the host’s innate responses. The project will be accomplished in close collaboration with Prof. Dr. Ulrike Seifert, Institute of Immunology, University of Madgeburg. Her work focusses on the investigation of the UPS in innate and acquired immunity (2,3). Our own work focusses on host-pathogen interactions in the airways of the human lung. We investigate the mechanisms of innate immune responses of the human host after infections with bacteríal infections (4). References: 1. Anas A., Wiersinga A., de Vos A., van der Poll T. Recent insights into the pathogenesis of sepsis. J Med. 2010 2. Seifert U, et al. Immunoproteasomes preserve protein homeostasis upon interferon-induced oxidative stress. Cell 2010;142:613-24 3. Kloetzel PM. Antigen processing by the proteasome. Nat Rev Mol Cell Biol. 2001;2:179-87. 4. Slevogt H. et al. CEACAM1 inhibits Toll-like receptor 2-triggered anti-bacterial responses of human pulmonary epithelial cells. Nat Immunol. 2008; 9:1270-78.