Vacancy Details
 |
|||||
| Date placed | 05-02-2010 | ||||
|
|||||
| Contact name | Dr. H. de Cock | ||||
|
|||||
| Contact email | h.decock@uu.nl | ||||
|
|||||
| Contact website | http:// | ||||
|
|||||
| Position available | PhD student | ||||
|
|||||
| Description | PhD scholarship Utrecht Microbiology, Department of Biology, Faculty of Science, Utrecht University Dr. Hans de Cock Prof Dr. H.A.B Wösten | ||||
|
|||||
| Short Title | Modulation of the immune response by Cryptococcus neoformans | ||||
|
|||||
| Full text | “Modulation of the immune response by Cryptococcus neoformans” How to survive in hosts and cause persistent infections. Cryptococcus neoformans, a human opportunistic pathogenic yeast, produces an extracellular polysaccharide capsule that is essential for pathogenesis. The capsule is composed of two different classes of polysaccharides, glucuronoxylomannan (GXM) and glucuronoxylomannangalactan (GXMGal). The GXM polysaccharides are structurally different between serotypes. Moreover, GXM is structurally variable within a serotype due to substoichiometric modifications by acetylation of mannoses (up to 10% in serotype D). In addition, xylosidation of GXM has been shown to vary and correlated with phenotypic switching. GXMGal differs strongly in the xylose content and, in addition, contains glucuronic acid in variable and substoichiometric amounts (Eukaryot Cell. 2009; 8(8):1165-73, Carbohydr Res. 2009; 344(7):915-20). The variability of the capsular polysaccharide structures of Cryptococcus neoformans are likely used to escape the immune response imposed by the human host. We recently demonstrated that dendritic cells (DCs) are not activated by wild type encapsulated cells of Cryptococcus of serotype A. A mutant, CAP59, lacking a visible capsule due to a mutation in a gene encoding an enzyme required for synthesis of GXM does activate maturation of DCs. However, the CAP10 mutant, also lacking a visible capsule, does not active DCs. Transfer of extracellular material from wild type cells to the CAP59 mutants cell surface, most likely GXM, converts CAP59 to a cell not able to induce maturation of DCs. Extracellular material of CAP10 transferred to CAP59 cells partly reduces the capacity of CAP59 to stimulate DC maturation (FEMS Immunol Med Microbiol. 2009; 57(2):142-50) The project is aimed to identify the extracellular components responsible for modulation of immune response, enabling Cryptococcus to survive in the human host. We focus specifically on the capsular polysaccharides since these components have been suggested to play a crucial role in pathogenesis. In addition, Cryptococcus is able to change the polysaccharide structures either during or after synthesis enabling the cells to adapt to different environments within the human host. The PhD scholarship (1400 € a month) is awarded for one year and can be extended for three times one year. The scholarship is only available for residents outside the European Union. The candidate should preferable have a background in Microbiology, Chemistry and/or Immunology, The project encompasses purification and characterization of various components requiring experience with carbohydrate analysis (chromatography/mass spectrometry/NMR). Please contact Hans de Cock if you are interested and/or requires more information. Dr. H. de Cock Microbiology & Institute of Biomembranes Dept. Biology, Faculty of Science Utrecht University Padualaan 8, room W 407 3584 CH Utrecht, The Netherlands H.R. Kruytgebouw Tel: (+31)-30-253 2267 Fax: (+31)-30-251 3655 | ||||
|
|||||