Several decades after the introduction of recombinant DNA technologies for heterologous protein
expression, it remains a matter of trial and error whether a given new protein or protein fragment will
express well in any given expression host cell.
In this project, we aim at developing a novel technology to enable the proteome-wide determination of
which soluble protein fragments can be produced in the yeast secretory system. Furthermore, the
technology will allow studying which soluble protein fragments depend on which secretory system
processes for their production. Within the scope of this project, we will focus on identifying the range of
(glyco)proteins that depend on the ER chaperone calnexin for their folding.
We will also explore how secretory system processes could be modified to expand the range of protein
fragments which can be successfully produced as soluble, secreted proteins by the yeast secretory system.
As an example, we will establish which proteins are influenced in their expression and secretion in yeast
in which the Unfolded Protein Response is induced.
Apart from enabling novel basic research about the functioning of the eukaryotic secretory system, the
project's outcomes should be of broad utility to anyone producing recombinant proteins for functional,
structural or therapeutics studies.