Dokument: The role of the Vip1 kinase family member Asp1 in the morphogenesis of the fission yeast Schizosaccharomyces pombe
| Titel: | The role of the Vip1 kinase family member Asp1 in the morphogenesis of the fission yeast Schizosaccharomyces pombe | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=47083 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20180913-081715-6 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Dr. Vangala, Anand Babu [Autor] | |||||||
| Dateien: |
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| Beitragende: | Dr. Fleig, Ursula Nicole [Gutachter] Prof. Dr. Hegemann, J. H. [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | The medical advancements in the last decades like, treatment of cancer by chemotherapy and the management of organ transplantation via immune suppressive medication have led to a massive increase of serious infections by pathogenic fungi. A vital virulence trait of life-threatening pathogenic fungi is their ability to undergo morphological transitions in response to external clues. Such an alteration in growth form is a conserved feature present in all fungi including the non-pathogenic model yeasts. Thus, elucidation of conserved molecular pathways essential for the dimorphic switch will contribute to understand fungal virulence mechanisms.
We have used the fission yeast Schizosaccharomyces pombe to identify the molecular regulators of this switch and were the first to demonstrate that inositol pyrophosphates (IPPs) generated by the Asp1 protein are essential for the dimorphic switch. Inositol pyrophosphates are conserved high energy signaling molecules. Asp1-like proteins are present in all eukaryotes and possess a dual domain structure consisting of an N-terminal "rimK"/ATP- grasp superfamily domain that generates 1,5-IP8 and a C-terminal domain with pyrophosphatase activity that specifically dephosphorylates 1,5-IP8 to 5-IP7. IPPs regulate a variety of cellular activities ranging from the human antiviral response to plant defense mechanisms against pathogens. It was shown that a correlation exists between the amount of 1,5-IP8 and the ability to switch. In the current study, it was identified that lower temperature and iron at toxic concentrations together with nutrient limitation can enhance the switching process.To understand exactly how 1,5-IP8 regulate the dimorphic switch, I analyzed adhesins as possible targets and identified the adhesin Gsf2 as one of the essential components required for Asp1 mediated dimorphic switch. Upregulation of gsf2+ increased the number of invasively growing colonies, but only in the presence of 1,5-IP8. Next, it was analyzed, if 1,5-IP8 regulate Gsf2 adhesin expression, and later identified to be true. The absence of cellular 1,5-IP8 negatively influenced gsf2+ expression and higher levels positively influenced gsf2+ expression. All the transcriptional activators that regulate Gsf2 adhesin are identified to be essential for the Asp1 mediated dimorphic switch. A yeast two-hybrid screen identified that, Met10 interacts with Asp1 and negatively regulates Asp1 pyrophosphatase activity in vitro and localizes to mitochondria in vivo. Surprisingly met10∆ strain did not show any difference in the IP8 levels in vivo. It can be hypothesized that Met10 acts as a negative regulator upstream of Asp1 to regulate the dimorphic switch as met10∆ strain showed enhanced number of invasively growing colonies. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie » Funktionelle Genomforschung der Mikroorganismen | |||||||
| Dokument erstellt am: | 13.09.2018 | |||||||
| Dateien geändert am: | 13.09.2018 | |||||||
| Promotionsantrag am: | 25.06.2018 | |||||||
| Datum der Promotion: | 25.07.2018 |
