Yeast-Glyco · Nucleocytoplasmic O-glycosylation in Yeast
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-10-01 → 2019-09-30
- EU contribution
- €278,228
- Participants
- 2
- Scheme
- MSCA-IF-GF
Lines connect the coordinator with its partners.
Results in brief
Nucleocytoplasmic O-glycosylation in Yeast
Saccharomyces cerevisiae, more commonly known as yeast, are single-cell organism predominantly responsible for breakdown (fermentation) of simple carbohydrates in nature. In science, yeast have for a long time been one of the best characterized organism from the genetic, biochemical and physiological point of view and are continuously used by scientist to explore and understand biological processes in higher eukaryotic organisms, which include e.g. plants, mammals and humans. Yeast utilize a biochemical process known as phosphorylation to control biological processes; specific biological functions, e.g. cell division or carbohydrate fermentation may be activated or deactivated in yeast by phosphorylation. Surprisingly, yeast lack the co-regulatory mechanisms known as O-GlcNAcylation, which is so commonly used by many other eukaryotic organisms (plants, mammals, humans etc.), to control many important biological functions. Dysregulation of O-GlcNAcylation is associated with human illness and it has remained a longstanding conundrum how yeast control biological functions without the involvement of O-GlcNAcylation. This project is based on our discovery demonstrating that yeast indeed have a co-regulatory mechanisms for controlling biological processes based on a similar mechanisms known as O-Mannosylation and aims to improve our understanding of O-Mannosylations in eukaryotes. More specifically, this research project aims to explore when and where yeast utilize the O-Mannosylation mechanism and how it functions in yeast cell biology. In addition, this project aims to identify and characterize the biosynthetic machineries responsible for O-Mannosylation in yeast. This research will bring novel knowledge on how yeast orchestrates biological processes and advance our understanding on how essential cellular functions are controlled in these organisms. In addition, this will allow us to extrapolate and understand how O-Mannosylation and O-GlcNAcylation functions in higher organisms (e.g. humans) which will improve our understanding of human diseases including diabetes and cancer. The overall objective is to use biochemical methods and state-of-art technologies (mass spectrometry) to: 1)identify which proteins undergo O-Mannosylation, 2) identify the biosynthetic machineries (enzymes) responsible for O-Mannosylation and 3) transfer knowledge for comparative studies on protein modifications (O-glycosylation) higher eukaryotes.
Data: CORDIS, © European Union
Project objective
Signal transduction via post-translational modifications (PTMs) of proteins maintains essential cellular processes in all eukaryotes. Similar to protein phosphorylation, O-GlcNAcylation is a vital signaling mechanism that involves the dynamic cycling of sugar molecules on proteins and these PTMs exhibit extensive crosstalk for regulation of core cellular processes. The only eukaryotic cell type that lacks both signaling mechanisms is yeast and it has been difficult to understand how yeast survive without the essential functions of O-GlcNAcylation. This proposal is based on our discovery demonstrating that baker’s yeast has an O-linked mannose (O-Man) glycosylation system that operates in nuclear, cytoplasmic and mitochondrial compartments. The localization of these O-Man modifications on yeast proteins mirrors that of O-GlcNAcylation found in higher eukaryotes and this discovery demonstrates that yeast possess a hitherto unknown signaling mechanism involved a myriad of cellular processes. This research project aims to explore when and where yeast utilize the nucleocytoplasmic O-Man signaling system and to understand the functional consequences of this novel modification. In addition, the project aims to identify and characterize the enzymes responsible for the attachment and removal of nucleocytoplasmic O-Man modifications in order to enable manipulation of the system for improvements in yeast-based bioproduction and bioprocessing platforms. The project will open an entirely new area of research by bringing novel knowledge on how yeast orchestrate cellular signaling and advance our understanding on how essential cellular processes are controlled in eukaryotes. This holds promise to bring unique opportunities to manipulate yeast for improvements and open for wide applications in industry and biotechnology.
Original text from CORDIS.
Participants
- KOBENHAVNS UNIVERSITET · KOBENHAVNCoordinatorDenmark
- THE ROCKEFELLER UNIVERSITY NOT FOR PROFIT CORPORATION · New YorkUnited States
Links
Data: CORDIS, © European Union
