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Dissecting the molecular mechanisms of protein glycosylation and glycoprotein trafficking in cereal endosperm

Objective

Plant-derived pharmaceuticals (PDPs) have immense potential to address the economic and capacity limitations of current fermenter-based production technology. Several complex multi-subunit and glycosylated proteins have been produced in transgenic plants, which are safe, convenient and cost-effective for large-scale production. High-biomass leaf and seed crops, such as maize and tobacco, are the most widely used. However, since most clinically-relevant recombinant proteins are glycosylated, one hurdle to the widespread commercial production of therapeutic proteins in plants is the fact that plant N-glycans differ from those found in humans, potentially limiting the therapeutic potential of PDPs. Glyco-engineering, to make plants that generate recombinant glycoproteins with human-like N-glycans is therefore an import goal. Most plant-derived glycoproteins studied thus far have a mix of N-glycans whose profile differs according to species, organ and physiological state. In maize seeds, we have shown that the N-glycans on a recombinant antibody were trimmed extensively, indicating the presence of ENGase activity in the endomembrane system of maize endosperm. In order to realize the greatest benefit from maize as a production system, it is important to characterize this enzymatic activity and the corresponding gene. We propose to utilize transgenic maize lines expressing two marker glycoproteins to monitor ENGase activity and subcellular localization in order to isolate, characterize and clone the ENGase gene. This will help in the development of a maize production system for improved glycoprotein therapeutics with appropriate glycans.

Call for proposal

FP7-PEOPLE-2007-4-3-IRG
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Coordinator

UNIVERSITAET FUER BODENKULTUR WIEN
Address
Gregor Mendel Strasse 33
1180 Wien
Austria
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 75 000
Administrative Contact
Eva Stoger (Prof.)