Out-licensing

Membrane Protein Expression System: Superior Membrane Protein Expression for Drug Discovery

Introduction/Background

Fungal infections in humans are opportunistic, often difficult to treat and sometimes fatal. There is rising resistance in many fungal pathogens to the limited number of antifungal drugs.

Aims/Hypothesis

Pharmaceutical companies face a lack of new drugs in their pipelines and are therefore seeking new drugs, drug classes and drug targets.

Research

Otago researchers developed a Membrane Protein Expression system that expresses any membrane protein required by research groups and companies. The system uses a Saccharomyces cerevisiae host (baker's yeast). Importantly, the expressed membrane protein is not species dependent and we have expressed a variety of fungal pathogen and human membrane proteins. Our system expresses the "foreign" membrane protein so that it is functional and located on the membrane as if it were expressed naturally. Our system consistently "over-expresses" the target at a high level and competing "background noise" of other unwanted membrane protein expression is minimised - improving protein crystallisation for identification and functional analysis. The Membrane Protein Expression system can also build the scaffolding for appropriate drug discovery screening models as it amplifies the feature of interest and identifies any interference with the expressed drug target.

We have multiple systems that express efflux pump membrane proteins. The pumps we have expressed transport specific compounds out of the cell, for example cancer therapeutics and antifungal treatments. The cancer drug pump is a human membrane protein, whereas the antifungal drug pump is a fungus specific drug pump. Finding drug pump inhibiting compounds leads to new combination therapies that address resistance. Using the system to undertake initial screening activities, in collaboration with external parties, we have identified a novel pump inhibitor for potential use with anti-fungals. This candidate is now under further investigation.

Conclusion

The present opportunity is a superior Membrane Protein Expression system to investigate and overcome drug resistance in fungal pathogens. In addition, the system has been further developed to aid in the discovery of new therapeutics targeting human membrane proteins.

Relevance/Opportunity

We are currently further developing our system to improve human membrane protein expression to develop drug targets for many major human diseases. The existing Membrane Protein Expression systems are available for licensing. We also offer the development (and licensing) of customised systems to express the membrane protein drug targets of interest and for its use in drug discovery screening models. Potential applications in malaria, crop protection, and development of a research kit for academia provide additional partnering opportunities. In the near future, we will seek investment for a company formation to undertake drug discovery and to extend uses of the Membrane Protein Expression system.

Registered

We have a number of granted and filed patents for the system.