Extracellular protein interaction screening technology

Many cellular communication events are triggered by direct interactions involving receptor proteins at the cell surface. These interactions are clinically useful because they can be manipulated by medicines such as therapeutic monoclonal antibodies. Detecting these extracellular interactions is difficult because membrane proteins are hard to solubilise and these interactions are often extremely transient, having half-lives of less than a second.

We have invented methods to detect this class of interactions in a large-scale systematic way. This includes our original AVEXIS (AVidity-based EXtracellular Interaction Screening) technique which detects direct binding events between soluble recombinant proteins expressed in mammalian cells. This method is highly scalable and gives robust binding signals with a low false positive rate. We continue to develop and refine this general approach which now allows us to test tens of thousands of receptor interactions. 
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We have also developed cell-based approaches based on loss and gain-of-function CRISPR technology to identify receptor interactions in the context of the plasma membrane on a genome-wide scale.​

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Host-pathogen interactions

To successfully infect other organisms, pathogens such as viruses and parasites must interact with the proteins of their host. 

At the molecular level, the first point of contact is often direct interactions between receptor proteins displayed at the surface of the host and pathogen. Discovering these interactions is an excellent way to understand how pathogens cause disease and develop better medicines and vaccines. 

Our AVEXIS approach is ideally suited to detect these binding events and we are using our technology to discover host receptors for viruses, and how parasites invade our cells and subvert host immunity. 

Currently, we are investigating how the parasite that causes severe malaria is able to manipulate host immunity using a family of highly polymorphic cell surface proteins known as RIFINs. ​

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Vaccine target identification for parasitic diseases

Vaccines are one of mankind’s greatest biomedical success stories saving many millions of lives. Developing vaccines for many viruses and some bacteria is now well-established, but vaccines for parasites is more challenging. 

We have used our expertise in recombinant protein expression to identify new parasite vaccine targets. Some of our work on host-pathogen interactions identified a new blood stage malaria vaccine known as RH5.
 
We have also identified vaccine targets for animal African trypanosomiasis, a parasitic disease of livestock animals that affects the lives and livelihoods of many people living in some of the most deprived regions of the world.

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