Investigate and determine the cellular constraints that limit the production of biotherapeutic medicines from prokaryotic and eukaryotic expression systems and, to develop experimentally verifiable predictive models based upon these data.
The scientific objectives within Theme 1 will be to investigate the cellular constraints that limit or enhance the expression of therapeutic protein molecules from bacterial, yeast and mammalian expression systems. The data from these studies will then be used to develop predictive models that work at either the molecular (predicting the impact of molecular characteristics on processing decisions, performance and product properties), cellular (the effect of perturbations of cellular characteristics and the environment on processing efficiency), or industrial scale levels with a view to enhancing the yields, activity and quality of therapeutic biomolecules and medicines. In doing this the following aspects will be focussed upon:
(a) mRNA translation and its control during molecular processing in yeast and mammalian cell systems;
(b) Determination of limitations on cell growth and cell-specific productivity and engineering strategies to improve these;
(c) Analysis of constraints throughout the gene expression pathway to define limitations in molecular processing of biomolecules;
(d) Design of biomolecules for more efficient molecular processing and enhanced efficacy;
(e) Gene expression and control with respect to perturbation of the cell environment and cell signalling and the effect on molecular processing of biomolecules;
(f) Understanding and preventing aggregation of both cytoplasmic and secretory proteins.