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

通过定量蛋白质组学定义植物与病原体相互作用的机制，以改进分子农业策略

• 批准号: 539389-2019
• 负责人: GeddesMcAlister, Jennifer
• 金额: $ 5.98万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=719877
• 关键词: Defining; mechanisms; plant; pathogen; interactions

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.

重组蛋白在植物中的瞬时表达越来越多地被用作治疗性蛋白如单克隆抗体、酶和疫苗的生产平台。该系统的好处包括降低药物开发成本，快速向市场交付新产品，以及为关节炎和癌症等疾病提供安全有效药物的能力。PlantForm公司是一家加拿大生物技术公司，开发了这样一种系统来生产生物仿制药（例如Humira®和Herceptin®）以及针对病原体（例如HIV和埃博拉病毒）的创新产品。PlantForm的技术被称为vivoXPRESS®，其基础是使用常见的植物病原体（根癌农杆菌）将编码特定蛋白质产物的基因传递到植物细胞（本氏烟草）。这种方法提供了一种技术，其中工厂成为制造所需产品的工厂。最近的NSERC参与赠款（2017）与博士。Allen-Vercoe（该NSERC CRD项目的合作者;圭尔夫大学）导致了使用微生物发酵生产农杆菌培养物的可扩展方法。然而，尽管取得了这些进展，从病原体和宿主的角度对农杆菌渗入的影响的全面理解还没有进行。在这里，拟议的研究项目直接建立在NSERC Engage资助的成功基础上，以描述A. tumefaciens和N.本塞姆氏菌属（benthamiana）在农杆菌渗透后进行的蛋白质生产，以确定生产过程中的步骤，该步骤可以针对最佳靶蛋白生产进行调整。该研究项目的结果将为病原体和宿主在感染过程中细胞水平的调控模式提供有价值的见解，并表征农杆菌蛋白质递送的机制。我们预计我们的结果将转化为蛋白质产量的大幅增加和PlantForm新产品开发的显着成本节约。最终，我们的目标是减少在加拿大生产新的、安全的和有效的治疗药物的障碍。