Defining mechanisms of plant-pathogen interactions by quantitative proteomics for improved strategies in molecular farming

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Transient expression of recombinant proteins in plants is increasingly being used as a production platform for therapeutic proteins such as monoclonal antibodies, enzymes, and vaccines. Benefits of this system include a reduced cost of drug development, rapid delivery of new products to the market, and an ability to provide safe and efficacious medicines for diseases such as arthritis and cancer. PlantForm Corporation is a Canadian biotechnology company that has developed such a system to produce biosimilar versions of therapeutics (e.g. Humira® and Herceptin®), as well as innovative products against pathogens (e.g. HIV and Ebola virus). The basis of PlantForm's technology, known as vivoXPRESS®, is to use a common plant pathogen (Agrobacterium tumefaciens) to deliver genes encoding for a specific protein product to plant cells (Nicotiana benthamiana). This approach provides a technology in which the plant becomes a factory for manufacturing of the desired product. A recent NSERC Engage grant (2017) with Dr. E. Allen-Vercoe (collaborator on this NSERC CRD project; University of Guelph) resulted in scalable methods using microbial fermentation for production of Agrobacterium cultures. However, despite these advances, a comprehensive understanding of the impact of Agrobacterium infiltration from both the pathogen and host perspectives, has not been performed. Here, the proposed research project builds directly upon the success of the NSERC Engage grant to profile differences in protein and metabolite abundance in A. tumefaciens and N. benthamiana following agroinfiltration to determine steps in the production process, which can be tailored for optimal target protein production. The results from this research project will provide valuable insight into patterns of regulation at the cellular level in the pathogen and host during infection and characterize mechanisms of protein delivery by Agrobacterium. We anticipate our results to translate into substantial increases in protein production and significant cost savings for new product development for PlantForm. Ultimately, we aim to reduce barriers for the production of new, safe, and effective therapeutics in Canada.