Project Title: Glyco-engineering of therapeutic proteins from microalgae
Supervisors: Prof Peter Ralph, Dr Manoj Kumar, Dr Matt Padula
I am an International PhD candidate in the Algal Biosystems and Biotechnology Group within the Climate Change Cluster (C3). I started my PhD at UTS in September 2016, after graduating (M.Sc.) in Biological Chemistry at Università degli Studi di Napoli "Federico II".
Biopharmaceuticals are recombinant therapeutic proteins that include vaccines, antibodies and hormones. They can be produced in a wide range of cell factories systems, such as bacteria, yeast, and mammalian cells. Among these systems, microalgae stand out as cheap, fast and easy to grow.
Unlike traditional drugs, biopharmaceuticals owe their efficiency to the post-translational modifications they undergo during protein expression. One of the most important ones is glycosylation, the covalent linkage of polysaccharide side chains to a protein, which is highly crucial in determining protein stability, activity, pharmacokinetic and immunogenicity.
Microalgae glycosylation patterns that occur in the Golgi complex differ from human glycosylation patterns and can lead to inactive or even harmful biopharmaceutical. Therefore, it is imperative to examine the capacity of microalgae to mimic the human-type glycosylation pattern to ensure these tiny wonders for pharmaceutical production are suitable for human therapy.
- Transform microalgae C. reinhardtii for the expression of Interferon α2a (IFN α2a) in a secreted and non-secreted manner;
- Screen the positive transformants, and subsequently generate enough recombinant protein to purify it for glycosylation studies;
- Analyse the glycosylation pattern of both secreted and non-secreted IFN α2a;
- Compare glycosylation patterns of both secreted and non-secreted IFN α2a expressed in C. reinhardtii with human and plant-expressed IFN α2a.
Improving our understanding of the intricacies of microlagal protein glycosylation systems is highly promising and may lead to new opportunities to manipulate these biochemical pathways in order to engineer glycoproteins with potential value as novel biopharmaceuticals. Such advancements of glyco-engineering of algal therapeutic proteins will greatly enhance their biopharmaceutical market globally.