Research

Plant innate immunity. Plants, unlike mammals, lack mobile defender cells and adaptive immune systems. Instead, they rely on the innate immunity of each cell, systemic peptide and chemical signals emanating from infection sites, and preformed and inducible chemical defenses at infection sites to ward off invading pathogens (1). Plant innate immunity is based on the perception and production of small molecules and rivals mammalian innate immunity in combating pathogenic infections.

Novel Immune Signals and Regulators. More than prokaryotes or animals, plants collectively produce hundreds of thousands of natural products (2-4), the majority of which are used in plant defense against microbial pathogens, insect herbivores and competitor plants. Only a tiny fraction of the plant natural product diversity is used in bioenergy, industry and human medicines. Yet, an estimated 74% of the most important human drugs in the 21st century contain plant-derived active ingredients (5-6), and about 75% of the global population still relies on plant-based traditional medicines for their primary health care (7). Despite their divergent structures and bioactivities, these phytochemicals are robustly integrated into the conserved framework of plant immune responses (8-9), conferring long-lasting immunity against a broad spectrum of microbes throughout the plant. The Clay lab exploits plant-pathogen interactions to discover novel immune signals and regulators of metabolite profiles required for basal and acquired disease resistance in plants.

Novel Protein Modifications and Quality-controls. Because plants and humans share the same pathways for protein synthesis, glycosylation and quality-control, plants have emerged as alternative hosts for the cost-effective, large-scale production of biopharmaceuticals and vaccines with defined human-like glycan structures (10-13). The complex ligand-binding structures of plant innate immune receptors require post-translational modifications and sophisticated protein quality control systems at multiple steps along the secretory pathway to recognize and eliminate misfolded, immature and unassembled proteins. The Clay lab re-engineers plant immune receptors to discover novel protein modifications and quality-controls that regulate recombinant (and native) protein production and function in plants.

 

  1. Jones, J. D., Dangl, J. L. (2006). The plant immune system. Nature 444, 323-329
  2. Dixon, R.A. (2001). Natural products and plant disease Nature 411, 843-84.
  3. Wink, M. (1988). Plant breeding: importance of plant secondary metabolites for protection against pathogens and herbivores. Theoretical and Applied Genetics 75, 225-233.
  4. Mohanta, T.K. (2013). Plant metabolomics: missing link in next generation functional genomics era. Journal of Applied Biology and Biotechnology 1, 1-10.
  5. Millimouno, F.M., Dong, J., Yang, L (2014). Targeting apoptosis pathways in cancer and perspectives with natural compounds from mother nature. Cancer Prevention Research 7, 1081-1107.
  6. Raskin, I., Ribnicky, D.M., Komarnytsky, S., et al. (2002). Plants and human health in the twenty-first century. Trends in Biotechnology 20, 522-531.
  7. Arvigo, R., Balick, M. (1993). Rainforest Remedies. Lotus Press: Twin Lakes, Colorado.
  8. Clay, N. K., Adio, A. M., Denoux, C., et al. (2009). Glucosinolate metabolites required for an Arabidopsis innate immune response. Science 323, 95-101.
  9. Ahmad, S., Veyrat, N., Gordon-Weeks, R., et al. (2011). Benzoxazinoid metabolites regulate innate immunity against aphids and fungi in maize. Plant Physiology 157, 317-327
  10. Castilho, A., Steinkellner, H. (2012). Glyco-engineering in plants to produce human-like N-glycan structures. Biotechnology Journal 7, 1088-1098.
  11. Bosch, D., Castilho, A., Loos, A., et al. (2013). N-glycosylation of plant-produced recombinant proteins. Current Pharmaceutical Design 19, 5503-5512.
  12. Gomord, V., Fitchette, A.C., Menu-Bouaouiche, L., et al. (2010). Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnology Journal 8, 564-587.
  13. Nagels, B., Weterings, K., Callewaert, N., et al. (2012). Production of plant made pharmaceuticals: from plant host to functional protein. Critical Reviews in Plant Sciences 31, 148-180.

 

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