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N-linked protein glycosylation: analysis of the bacterial and the eukaryotic oligosaccharyltransferase

English title N-linked protein glycosylation: analysis of the bacterial and the eukaryotic oligosaccharyltransferase
Applicant Aebi Markus
Number 105541
Funding scheme Project funding
Research institution Institut für Mikrobiologie Departement Biologie ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Resource not found: 'a21e0013-75a3-417f-aca2-51547398bba1' Cellular Biology, Cytology
Resource not found: '93d4f2ee-a6aa-43d4-b606-c789b39e2fd8' 01.11.2004 - 31.10.2009
Approved amount 1'061'423.00
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All Disciplines (2)

Discipline
Cellular Biology, Cytology
Experimental Microbiology

Keywords (3)

N-linked protein glycosylation; Yeast; Escherichia coli

Lay Summary (English)

Lead
Lay summary
This research project deals with the process of N-linked protein glycosylation, the most frequent protein modification in eukaryotic cells. We have used the yeast model system to characterize this biosynthetic process that takes place at the membrane of the Endoplasmic Reticulum and we applied our know-how for the identification and characterization of human inherited diseases where N-linked protein glycosylation is affected.During the past few years, our research has become a novel direction due to the discovery of a bacterial N-glycosylation process. We were able to transfer the genetic information encoding all the necessary components of this pathway from the original host Campylobacter jejuni to the model system Escherichia coli. The pathway is functional in this bacterium as well, enabling us to study the molecular mechanisms of N-linked protein glycosylation in more detail. It was shown that prokaryotic and eukaryotic N-glycosylation are homologous processes and that general mechanistic concepts can now be evaluated in E. coli.In the current project, we plan to identify small chemical compounds that inhibit defined steps of the prokaryotic N-glycosylation pathway. For this purpose, we use E.coli cells that N-glycosylate a marker protein and well screen a chemical library for components that prevent the glycosylation of this marker protein. A robotized read-out system has to be developed for this purpose. Potential N-glycosylation inhibitors will be tested in the original host C. jejuni, a human pathogen.Similar to the N-glycosylation system of C. jejuni, there seem to be N-glycosylation systems in lower eukaryotes that are less complex than the ones found in fungi or mammals. In the second part of this project we want to transfer the N-glycosylation functionalities of such lower eukaryotes into a good experimental system (Saccharomyces cerevisiae) and define the molecular mechanisms of this glycosylation system. It is possible that such simple eukaryotic systems can be used in biotechnological processes for the production of N-glycoproteins.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
127098 Concepts in N-linked protein glycosylation: Flippase and Oligosaccharyltransferase 01.11.2009 Project funding
57082 N-linked protein glycosylation in the endoplasmic reticulum of saccharomyces cerevisiae 01.10.1999 Project funding

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