ASU SoLS Faculty: Hugh S. Mason

My research involves genetic engineering of plants for recombinant protein production and improved quality traits, with a major focus on vaccines. My lab also works on the regulation of plant gene expression and multimeric protein assembly, with the aim of optimizing accumulation of foreign proteins in plants, and the testing of plant-derived vaccines by oral delivery in model test animals. The research comprises 3 main categories:

Plant-based vaccine production and testing. We use plants (potato, tomato, tobacco, alfalfa, and corn) as hosts for stable transformation and expression of vaccine antigens in edible tissues. Expression of foreign genes in plants may present challenging problems including transcription and mRNA processing, translation, assembly, and subcellular targeting. Since vaccine genes originate in diverse sources whose systems may be suboptimal for plant expression, we analyze coding sequences to identify potentially detrimental motifs that could mediate mRNA truncation or degradation, including polyadenylation signals, intron splice sites, and RNA instability motifs. We then use this information to design plant-optimized genes using plant-preferred codons. My lab has developed a number of useful expression cassettes using constitutive, chemically inducible, or tissue-specific promoters, viral translational enhancers, and efficient 3 elements, which we use routinely for antigen expression. After regeneration of the transgenic plant lines, we verify antigen expression and structure using specific immunoassays and biochemical characterization, then we use the edible material for animal trials to assess immunogenicity. Currently funded work in my laboratory includes development of plant-based vaccines for hepatitis B (NIH), human papillomavirus (NIH), Norwalk-like viruses (Japan Health Sciences Foundation), enteropathogenic E. coli (NIH), and plague (Department of Defense).

Novel plant gene expression systems. We are investigating the use of plant geminivirus elements to enhance the expression of foreign proteins in a tightly regulated manner. High expression of foreign proteins often causes toxic effects in plant cells and may interfere with plant growth and development. Thus regulated expression is necessary in order to obtain the most efficient protein production. Incorporation of expression cassettes within viral replicons that can be replicated in trans by a viral factor (Rep) expressed from an inducible promoter yields high copy number of the cassette and maximizes the transcription. This work is currently supported by two grants from NSF for 1) use of geminivirus elements to enhance transient protein expression in plant cell and root cultures, and 2) stable expression of recombinant proteins in plant cell cultures using regulated geminivirus-mediated gene amplification.

Multimeric protein assembly in plant cells. Using model vaccine antigens, we are investigating the synthesis, processing, and assembly of multimeric protein complexes in plants.