Protein Expression

Since the early 1980s living cells, such as bacteria, yeast and mammalian cells, have been used to produce proteins that can be incorporated into drugs. Theoretically the more protein that can be produced from a single cell, the cheaper drug manufacturing becomes, due to reduced resources required such as growth medium. Faster developing times will also reduce costs as identifying high producing strains can be time consuming and costly.

Our group works on different organisms to increase the amount of proteins produced or increase the purity of proteins. We also look at expressing proteins that may be beneficial for the future.

Yeast

The yeast Pichia pastoris has been used for 30 years for the production of proteins used in drugs. We work on a variety of methods to increased the amount of proteins produced, as well as looking at novel targets that have not been expressed before in P. pastoris.

Increasing Copy Number

One way to increase the amount of protein is to increase the number of foreign genes inserted into the yeast. We pioneered a new methodology to do this. Previosuly increasing the amount of selection over time results in higher number of genes inserted, but this was done on plates, which takes longer. We utilised a liquid based system that we called Liquid Posttransformational Vector Amplification (PTVA). You can read about it here.

Changing the Secretion Signal

When producing proteins in P. pastoris it's possible to direct the proteins out of the cell, this makes it much easier to purify them and cheaper for downstream processing. It's been shown that different signal peptides can result in different amounts of proteins produced. When expressing an anti-HIV antibody, VRC01, we have used an novel murine IgG1 signal peptide that resulted in higher yields of protein. You can read about some of our work into signal peptides here and here.