A (Alex) van der Kaaij MSc

A (Alex) van der Kaaij MSc

PhD student

Research

Heart failure has become a modern epidemic, with an overall prevalence of 2% in the western world. Despite advances in medical and device therapy, the five year mortality is still 50%. For patients with advanced heart failure a heart transplantation is the only curative option. However, due to the extreme shortage of usable donor hearts many patients die on the waiting list. Although the shortage of donor organs is partially caused by an insufficient number of registered donors, an equally important cause is the limited quality and matching of potential donor organs. The main reason for this is the current maximum 4 hour preservation time (from excision to implantation). In order to extend the preservation time, the hearts need to be frozen with extreme control and without ice formation. By taking inspiration from naturally occurring ice-binding proteins (IBPs), especially antifreeze glycoprotein (AFGP), new cryoprotectants can be developed to extend heart “life-time” ex vivo.

In this project, antifreeze glycoprotein will be developed and produced in Nicotiana bentamiana, which will serve as a glycoprotein production platform. By introducing new post-translational machinery in the plant, sugar motifs are introduced that are crucial for the functioning of the AFGP. Besides developing antifreeze glycoprotein, the effect of interfering glycosyl hydrolases and the newly introduced post-translational machinery will be studied. This knowledge will be used to finetune the production of AFGP.